Analogs of vincamine and uses thereof

Abstract

The present disclosure provides compounds of any one of Formulae (I′), (I), (IA), (II′), (II), (IIA), (IIIA), (III″), (III′), (III), (IIIA), (IV), (V′), (V), (VI), (VII), (VIII′), (VIII), (IX′), (IX), and (X). The compounds described herein may be useful in treating and/or preventing a broad range of diseases (e.g., proliferative disease (e.g., cancers (e.g., non-small cell lung cancer, or glioma), inflammatory diseases, autoimmune diseases), CNS disorder (e.g., drug addiction), metabolic disorder (e.g., diabetes), or infectious disease (e.g., bacterial infection or parasitic infection (e.g., malaria))). Also provided in the present disclosure are pharmaceutical compositions, methods of synthesis of a compound described herein, kits, methods, and uses including or using a compound described herein. ##STR00001## ##STR00002## ##STR00003## ##STR00004##

Claims

1. A compound of Formula (VII): ##STR00232## or a pharmaceutically acceptable salt thereof, wherein: R.sup.A2 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; R.sup.B6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; each instance of R.sup.D5 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a; each instance of R.sup.D6 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a; R.sup.F1 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a; each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl; j is 1, 2, 3, or 4; and k is 1, 2, 3, or 4.

2. The compound of claim 1, wherein R.sup.A2 is optionally substituted C.sub.1-6 alkyl, optionally substituted alkynyl, optionally substituted carbocyclyl, or optionally substituted aryl.

3. The compound of claim 2, wherein R.sup.A2 is n-butyl.

4. The compound of claim 2, wherein R.sup.A2 is of the formula: —(CH.sub.2).sub.xR.sup.A2b, wherein: x is 1, 2, 3, or 4; and R.sup.A2b is optionally substituted alkynyl, optionally substituted carbocyclyl, of optionally substituted aryl, or optionally substituted heteroaryl.

5. The compound of claim 2, wherein R.sup.A2 is of the formula: ##STR00233##

6. The compound of claim 1, wherein R.sup.F1 is optionally substituted C.sub.1-6 alkyl.

7. The compound of claim 6, wherein R.sup.F1 is ethyl.

8. The compound of claim 1, wherein j is 1 and k is 1.

9. The compound of claim 1, wherein R.sup.D5 and R.sup.D6 are both hydrogen.

10. The compound of claim 2, wherein R.sup.2 is optionally substituted 3- to 7-membered, monocyclic carbocyclyl comprising zero double bonds in the carbocyclic ring system.

11. The compound of claim 2, wherein R.sup.A2 is optionally substituted alkynyl.

12. The compound of claim 1, wherein R.sup.F1 is optionally substituted alkyl.

13. The compound of claim 1, wherein R.sup.B6 is hydrogen.

14. The compound of claim 1, wherein R.sup.A2 is optionally substituted 6- to 10-membered aryl.

15. The compound of claim 1, wherein R.sup.A2 is optionally substituted C.sub.2-6 alkynyl.

16. The compound of claim 1, wherein R.sup.A2 is optionally substituted C.sub.1-6 alkyl.

17. The compound of claim 1, wherein R.sup.A2 is of the formula: ##STR00234##

18. The compound of claim 1, wherein the compound is of formula: ##STR00235## or a pharmaceutically acceptable salt thereof.

19. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable excipient.

20. A method of treating a proliferative disease, a metabolic disorder, drug addiction, or an infectious disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

21. The method of claim 20, wherein the method is for treating a proliferative disease.

22. The method of claim 20, wherein the drug addiction is addiction to an opioid.

23. The method of claim 20, wherein the method is for treating a metabolic disorder.

24. The method of claim 20, wherein the method is for treating a drug addiction.

25. The method of claim 20, wherein the method is for treating an infectious disease.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The accompanying drawings, which constitute a part of this specification, illustrate several embodiments of the invention and together with the description, serve to explain the principles of the invention.

(2) FIG. 1. Exemplary Synthetic Scheme Toward Diverse and Complex Small Molecules Derived from Vincamine.

(3) FIG. 2. Ring Distortion and Diversification of Vincamine. Conditions for the synthetic steps are as follows: a) Methyl Propiolate (1.5 eq), CH3CH2OH, reflux, 2 h; b) 3M CNBr (3.0 eq), DMF, μw, 100° C., 6 min; c) NaN3, DMF, μw, 100° C., 6 min; d) 2-ethynylthiophene (3.0 eq), CuSO4 (47 mol %), Sodium Ascorbate (1.5 eq), (t-BuOH:H2O) (2:1), DCM, 2.5 h; e) LAH (5.0 eq), THF, 0° C.-RT; f) NaIO4 (5.0 eq), (THF:H2O) (3:1), 2 h g) KOH (5.3 eq), (CH3CH2OH:H2O) (2:1) μw, 180° C., 10 min; h) X═N, methyl chloroformate (1.2 eq), cyclopentylamine (10 eq), Et3N (1.1 eq), cat. DMAP, DCM, 4 h; i) X═O, K2CO3 (2.0 eq), allyl bromide (1.2 eq), DMF, 2 h; j) 3.0M CNBr (2.0 eq), (CHCl3:CH3OH) (3:1), 5 h; k) 12 (4.1 eq), (sat. aq. NaHCO3:CHCl) (1:2), 2 h; 1) 3-methoxyphenylboronic acid (1.05 eq), Pd(OAc)2 (24 mol %), K2CO3 (3.0 eq), MeOH, 4 h; m) 40 μM Methylene Blue, CH3OH, 24 hours.

(4) FIG. 3. Vincamine Analog Compound Library.

(5) FIG. 4: High Throughput Screening and Compound Libraries. High Throughput Screening was conducted under standard conditions.

(6) FIG. 4A: Heat Map Matrix of Biological Activity.

(7) FIG. 4B. Effect of Exemplary Compounds (V, V1a, V1p, V2a, V3a, V3b, V4a, V5a, and Y) Against Certain G Protein-Coupled Receptors (GPCR's) and Exemplary Contemplated Therapy or Probe Use.

(8) FIG. 4C. Hit Scaffolds with Differential Antagonistic Activity Against G Protein-Coupled Receptors (GPCR) Drug Targets, Relevant for Exemplary Therapeutic Effects Against Diseases. Depicted are IC.sub.50 values against GPCR Drug Targets. Assays for IC.sub.50 values were conducted via techniques recognized by one of ordinary skill in the art.

(9) FIG. 5. Complexity-to-Diversity: Approach and Application.

(10) FIG. 6. Complex and Diverse Small Molecules from Vincamine.

(11) FIG. 7. Ring Cleavage and Diversification from Vincamine.

(12) FIG. 8: Ring Distortion of Vincamine Leads to Interesting Reactivity.

(13) FIG. 9. Tryptoline Ring Distortion of Complex Indole Alkaloids

(14) FIG. 9A. Application of Analogs Resulting from Tryptoline Ring Distortion of Complex Indole Alkaloids from FIG. 9.

(15) FIG. 10. Exemplary Small Molecules Derived from Vincamine.

(16) FIG. 11. Unanticipated Reactivity of Vincamine Analogs Leading to Novel Compounds.

(17) FIG. 12. Physicochemical Analysis of Ring Distortion Libraries of Alkaloids including Vincamine to ChemBridge and Top FDA Approved Drugs.

(18) FIG. 13. Exemplary Medicinally Relevant Indole-Based Compounds with Diverse Targets and Activities.

(19) FIG. 14. Graph Showing Exemplary Compound (V2a) Inhibits Morphine Reinstatement in Mouse Model of Heroin Addiction. Stress-Induced Reinstatement of Morphine-Conditioned Place Preference in Mice. Depicted is the difference in time spent on morphine paired side in a mouse model (See protocol described in e.g., Shaham Y, Stewart J., Psychopharmacology (Berl). 1995 June; 119(3):334-41), including under the forced swim stress test. See Porsolt, Nature. 1977; 266:730-732; see also Archives internationales de pharmacodynamie et de therapie. 1977; 229:327-336.

(20) FIG. 15. Exemplary synthesis of analogs of vincamine via diverse and complex indole-like scaffolds, via ring cleavage, ring fusion, and/or ring rearrangement, starting from vincamine. Also depicted is an X-ray structure of an exemplary compound (V31).

(21) FIG. 16A. Raw crystal data and atomic numbering for V29.

(22) FIG. 16B. Refined crystal image of V29. Refined images were generated from Ortep3 and POV-Ray v3.7 programs from the raw X-Ray CIF file.

(23) FIG. 17A. Raw crystal data and atomic numbering for V67.

(24) FIG. 17B. Refined crystal image of V67. Refined images were generated from Ortep3 and POV-Ray v3.7 programs from the raw X-Ray CIF file.

(25) FIG. 18A. Raw crystal data and atomic numbering for V89.

(26) FIG. 18B. Refined crystal image of V89. Refined images were generated from Ortep3 and POV-Ray v3.7 programs from the raw X-Ray CIF file.

(27) FIG. 19. Graph of NQ01 Expression in LNCaP cells via ARE luciferase assay in LNCaP cells.

DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS OF THE INVENTION

(28) The present invention provides compounds, for the prevention and/or treatment of a disease of a subject. The present invention further provides methods of using the compounds described herein, e.g., as therapeutics, e.g., in the prevention and/or treatment of diseases. The diseases include, but are not limited to, cancer (e.g., leukemia, melanoma, multiple myeloma), inflammatory diseases, CNS disorders, and infectious diseases. Also provided by the present disclosure are pharmaceutical compositions, methods of synthesis of a compound described herein, kits, methods, and uses of a compound of Formulae (I′), (I), (IA), (II′), (II), (IIA), (III″), (III′), (IIIA), (III), (IV), (V′), (V), (VI), (VII), (VIII′), (VIII), (IX′), (IX), and (X), as described herein.

(29) Compounds

(30) 49 In certain embodiments, a compound described herein is a compound of any one of Formulae (I′), (I), (IA), (II′), (II), (IIA), (III″), (III′), (IIIA), (III), (IV), (V′), (V), (VI), (VII), (VIII′), (VIII), (IX′), (IX), and (X), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(31) In one aspect of the present invention, provided are compounds of Formula (I′):

(32) ##STR00046##
and pharmaceutically acceptable salts, solvates, hydrates, tautomers, and stereoisomers thereof, wherein:

(33) R.sup.1 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(34) each instance of R.sup.2 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(35) R.sup.3 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(36) R.sup.4′ is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;

(37) R.sup.4a is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —OR.sup.a, —C(═O)OR.sup.4, —N(R.sup.b).sub.2, or —SR.sup.a;

(38) R.sup.5 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(39) R.sup.5a is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.5, —N(R.sup.b).sub.2, or —SR.sup.a;

(40) R.sup.6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(41) R.sup.6a is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —OR.sup.6, —N(R.sup.b).sub.2, or —SR.sup.a, or optionally R.sup.4a and R.sup.6a are taken together to form ═O;

(42) each instance of R.sup.7 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(43) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(44) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(45) a1 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and

(46) b1 is 0, 1, 2, 3, or 4.

(47) In certain embodiments, a compound of Formula (I′) is of Formula (I).

(48) In one aspect of the present invention, provided are compounds of Formula (I):

(49) ##STR00047##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(50) R.sup.1 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(51) each instance of R.sup.2 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(52) R.sup.3 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(Rb).sub.2, or —SR.sup.a;

(53) R.sup.4 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;

(54) R.sup.5 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(55) R.sup.6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(56) each instance of R.sup.7 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(57) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(58) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(59) a is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and

(60) b is 1, 2, 3, or 4.

(61) In certain embodiments, a compound described herein is of Formula (IA):

(62) ##STR00048##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:
R.sup.1 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(63) each instance of R.sup.2 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(64) R.sup.3 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(65) R.sup.4 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;

(66) R.sup.5 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(67) R.sup.5a is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.5, —N(R.sup.b).sub.2, or —SR.sup.a;

(68) R.sup.6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(69) each instance of R.sup.7 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(70) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(71) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(72) a is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and

(73) b is 1, 2, 3, or 4.

(74) In certain embodiments, a compound described herein is of Formula (IA′):

(75) ##STR00049##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(76) R.sup.1, R.sup.2, R.sup.3, R.sup.5, R.sup.6, R.sup.7, a, and b are as defined herein for (I′) and (I);

(77) a1 is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and

(78) b1 is 1, 2, 3, or 4.

(79) Compounds of Formulae (I′), (I), (IA), and (IA′) include R. In certain embodiments, R.sup.1 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group. In certain embodiments, R.sup.1 is hydrogen. In certain embodiments, R.sup.1 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.1 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.1 is of the formula:

(80) ##STR00050##
wherein: R.sup.1A is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —OR.sup.a, or —N(R.sup.b).sub.2, and R.sup.a and R.sup.b are as defined herein. In certain embodiments, R.sup.1 is of the formula:

(81) ##STR00051##

(82) Compounds of Formulae (I′), (I), (IA), and (IA′) include one or more instances of R.sup.2. In certain embodiments, a is 1. In certain embodiments, a is 2. In certain embodiments, a is 3. In certain embodiments, a is 4. In certain embodiments, a is 5. In certain embodiments, a is 6. In certain embodiments, a is 7. In certain embodiments, a is 8. In certain embodiments, a is 9. In certain embodiments, a is 10. In certain embodiments, a1 is 0. In certain embodiments, a1 is 1. In certain embodiments, a1 is 2. In certain embodiments, a1 is 3. In certain embodiments, a1 is 4. In certain embodiments, a1 is 5. In certain embodiments, a1 is 6. In certain embodiments, a1 is 7. In certain embodiments, a1 is 8. In certain embodiments, a1 is 9. In certain embodiments, a1 is 10. In certain embodiments, at least one instance of R.sup.2 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a. In certain embodiments, at least one instance of R.sup.2 is hydrogen. In certain embodiments, at least one instance of R.sup.2 is halogen (e.g., F, Cl, Br, or I). In certain embodiments, at least one instance of R.sup.2 is —CN. In certain embodiments, at least one instance of R.sup.2 is substituted or unsubstituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, at least one instance of R.sup.2 is substituted or unsubstituted methyl. In certain embodiments, at least one instance of R.sup.2 is substituted or unsubstituted ethyl. In certain embodiments, at least one instance of R.sup.2 is substituted or unsubstituted propyl. In certain embodiments, at least one instance of R.sup.2 is halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a.

(83) Compounds of Formulae (I′), (I), (IA), and (IA′) include R.sup.3. In certain embodiments, R.sup.3 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a. In certain embodiments, R.sup.3 is hydrogen. In certain embodiments, R.sup.3 is halogen (e.g., F, Cl, Br, or I). In certain embodiments, R.sup.3 is —CN. In certain embodiments, R.sup.3 is —SCN. In certain embodiments, R.sup.3 is —NO.sub.2. In certain embodiments, R.sup.3 is —N.sub.3. In certain embodiments, R.sup.3 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.3 is substituted methyl. In certain embodiments, R.sup.3 is unsubstituted methyl. In certain embodiments, R.sup.3 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.3 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.3 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.3 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.3 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.3 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.3 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.3 is optionally substituted benzyl. In certain embodiments, R.sup.3 is optionally substituted phenyl. In certain embodiments, R.sup.3 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.3 is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, R.sup.3 is —OH. In certain embodiments, R.sup.3 is —OMe. In certain embodiments, R.sup.3 is —N(R.sup.b).sub.2 (e.g., —NMe.sub.2). In certain embodiments, R.sup.3 is —NMe.sub.2. In certain embodiments, R.sup.3 is —SR.sup.a (e.g., —SH, —SMe). In certain embodiments, R.sup.3 is optionally substituted sulfonyl. In certain embodiments, R.sup.3 is halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a.

(84) Compounds of Formula (I) include R.sup.4. In certain embodiments, R.sup.4 is hydrogen. In certain embodiments, R.sup.4 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.4 is substituted methyl. In certain embodiments, R.sup.4 is unsubstituted methyl. In certain embodiments, R.sup.4 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.4 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.4 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.4 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.4 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.4 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.4 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.4 is optionally substituted benzyl. In certain embodiments, R.sup.4 is optionally substituted phenyl. In certain embodiments, R.sup.4 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.4 is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl.

(85) Compounds of Formula (I′) include R.sup.4a. In certain embodiments, R.sup.4a is hydrogen. In certain embodiments, R.sup.4a is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.4a is substituted methyl. In certain embodiments, R.sup.4a is unsubstituted methyl. In certain embodiments, R.sup.4a is substituted or unsubstituted ethyl. In certain embodiments, R.sup.4a is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.4a is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.4a is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.4a is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.4a is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.4a is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.4a is optionally substituted benzyl. In certain embodiments, R.sup.4a is optionally substituted phenyl. In certain embodiments, R.sup.4a is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.4a is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, R.sup.4a is —C(═O)OR.sup.a (e.g., —C(═O)OH or —C(═O)OMe). In certain embodiments, R.sup.4a is —OH. In certain embodiments, R.sup.4a is —OMe. In certain embodiments, R.sup.4a is —N(R.sup.b).sub.2 (e.g., —NMe.sub.2). In certain embodiments, R.sup.4a is —NMe.sub.2. In certain embodiments, R.sup.4a is —SR.sup.a (e.g., —SMe). In certain embodiments, R.sup.4a is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —OR.sup.a, —C(═O)OR.sup.4, —N(R.sup.b).sub.2, or —SR.sup.a.

(86) Compounds of Formulae (I′), (IA), and (IA′) include R.sup.5a. In certain embodiments, R.sup.5a is hydrogen. In certain embodiments, R.sup.5a is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.5a is substituted methyl. In certain embodiments, R.sup.5a is unsubstituted methyl. In certain embodiments, R.sup.5a is substituted or unsubstituted ethyl. In certain embodiments, R.sup.5a is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.5a is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.5a is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.5a is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.5a is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.5a is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.5a is optionally substituted benzyl. In certain embodiments, R.sup.5a is optionally substituted phenyl. In certain embodiments, R.sup.5a is of the formula:

(87) ##STR00052##
wherein R.sup.z is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a; and z is 0, 1, 2, 3, 4, or 5. In certain embodiments, R.sup.5a is of the formula

(88) ##STR00053##

(89) In certain embodiments, R.sup.5a is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.5a is optionally substituted sulfonyl. In certain embodiments, R.sup.5a is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, R.sup.5a is —OH. In certain embodiments, R.sup.5a is —O(R.sup.5), wherein R.sup.5 is optionally substituted alkyl or optionally substituted aryl. In certain embodiments, R.sup.5a is —O(substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.5a is —OMe. In certain embodiments, R.sup.5a is —OEt. In certain embodiments, R.sup.5a is —O(iPr). In certain embodiments, R.sup.5a is —O(n-Bu). In certain embodiments, R.sup.5a is —O(optionally substituted phenyl). In certain embodiments, R.sup.5a is —OPh. In certain embodiments, R.sup.5a is —N(R.sup.b).sub.2 (e.g., —NH.sub.2, —NMe.sub.2). In certain embodiments, R.sup.5a is —NMe.sub.2. In certain embodiments, R.sup.5a is —SR.sup.a (e.g., —SMe). In certain embodiments, R.sup.5a is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.5, —N(R.sup.b).sub.2, or —SR.sup.a.

(90) Compounds of Formulae (I′), (I), (IA), and (IA′) include R.sup.5. In certain embodiments, R.sup.5 is hydrogen. In certain embodiments, R.sup.5 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.5 is substituted methyl. In certain embodiments, R.sup.5 is unsubstituted methyl. In certain embodiments, R.sup.5 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.5 is unsubstituted ethyl. In certain embodiments, R.sup.5 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.5 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.5 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.5 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.5 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.5 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.5 is optionally substituted benzyl. In certain embodiments, R.sup.5 is optionally substituted phenyl. In certain embodiments, R.sup.5 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.5 is an oxygen protecting group. In certain embodiments, R.sup.5 is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group.

(91) Compounds of Formula (I′) include R.sup.6a. In certain embodiments, R.sup.6a is hydrogen. In certain embodiments, R.sup.6a is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.6a is substituted methyl. In certain embodiments, R.sup.6a is unsubstituted methyl. In certain embodiments, R.sup.6a is substituted or unsubstituted ethyl. In certain embodiments, R.sup.6a is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.6a is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.6a is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.6a is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.6a is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.6a is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.6a is optionally substituted benzyl. In certain embodiments, R.sup.6a is optionally substituted phenyl. In certain embodiments, R.sup.6a is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.6a is —OR.sup.6 (e.g., —OH, —OMe, or —OPh). In certain embodiments, R.sup.6a is —OH. In certain embodiments, R.sup.6a is —OMe. In certain embodiments, R.sup.6a is —N(R.sup.b).sub.2 (e.g., —NMe.sub.2). In certain embodiments, R.sup.6a is —NMe.sub.2. In certain embodiments, R.sup.6a is —SR.sup.a (e.g., —SMe). In certain embodiments, R.sup.4a and R.sup.6a are taken together to form ═O. In certain embodiments, R.sup.4a and R.sup.6a are both hydrogen. In certain embodiments, R.sup.6a is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —OR.sup.6, —N(R.sup.b).sub.2, or —SR.sup.a, or optionally R.sup.4a and R.sup.6a are taken together to form ═O.

(92) Compounds of Formulae (I′), (I), (IA), and (IA′) include R.sup.6. In certain embodiments, R.sup.6 is hydrogen. In certain embodiments, R.sup.6 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.6 is substituted methyl. In certain embodiments, R.sup.6 is unsubstituted methyl. In certain embodiments, R.sup.6 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.6 is unsubstituted ethyl. In certain embodiments, R.sup.6 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.6 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.6 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.6 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.6 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.6 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.6 is optionally substituted benzyl. In certain embodiments, R.sup.6 is optionally substituted phenyl. In certain embodiments, R.sup.6 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.6 is an oxygen protecting group. In certain embodiments, R.sup.6 is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group.

(93) Compounds of Formulae (I′), (I), (IA), and (IA′) include one or more instances of R.sup.7. In certain embodiments, b is 1. In certain embodiments, b is 2. In certain embodiments, b is 3. In certain embodiments, b is 4. In certain embodiments, b1 is 0. In certain embodiments, b1 is 1. In certain embodiments, b1 is 2. In certain embodiments, b1 is 3. In certain embodiments, b1 is 4. In certain embodiments, b is b1.

(94) In certain embodiments, at least one instance of R.sup.7 is hydrogen. In certain embodiments, at least one instance of R.sup.7 is halogen (e.g., F, Cl, Br, or I). In certain embodiments, at least one instance of R.sup.7 is —CN. In certain embodiments, at least one instance of R.sup.7 is —SCN. In certain embodiments, at least one instance of R.sup.7 is —NO.sub.2. In certain embodiments, at least one instance of R.sup.7 is —N.sub.3. In certain embodiments, at least one instance of R.sup.7 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, at least one instance of R.sup.7 is substituted methyl. In certain embodiments, at least one instance of R.sup.7 is unsubstituted methyl. In certain embodiments, at least one instance of R.sup.7 is substituted or unsubstituted ethyl. In certain embodiments, at least one instance of R.sup.7 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, at least one instance of R.sup.7 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, at least one instance of R.sup.7 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, at least one instance of R.sup.7 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, at least one instance of R.sup.7 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R.sup.7 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, at least one instance of R.sup.7 is optionally substituted benzyl. In certain embodiments, at least one instance of R.sup.7 is optionally substituted phenyl. In certain embodiments, at least one instance of R.sup.7 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R.sup.7 is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, at least one instance of R.sup.7 is —OH. In certain embodiments, R.sup.7 is —OMe. In certain embodiments, at least one instance of R.sup.7 is —N(R.sup.b).sub.2 (e.g., —NMe.sub.2). In certain embodiments, at least one instance of R.sup.7 is —NMe.sub.2. In certain embodiments, at least one instance of R.sup.7 is —SR.sup.a (e.g., —SMe). In certain embodiments, at least one instance of R.sup.7 is optionally substituted sulfonyl. In certain embodiments, at least one instance of R.sup.7 is halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a.

(95) In certain embodiments, each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom. In certain embodiments, each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl. In certain embodiments, at least one instance of R.sup.a is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom.

(96) In certain embodiments, at least one instance of R.sup.b is hydrogen. In certain embodiments, at least one instance of R.sup.b is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl.

(97) In certain embodiments, a compound of Formula (I′), (I), (IA), or (IA′) is of the formula:

(98) ##STR00054##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(99) In certain embodiments, a compound of Formula (I′), (I), (IA), or (IA′) is of the formula:

(100) ##STR00055##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(101) Exemplary compounds of Formula (I′), (I), (IA), and (IA′) include, but are not limited to:

(102) ##STR00056## ##STR00057## ##STR00058## ##STR00059##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(103) In one aspect of the present invention, provided are compounds of Formula (II′):

(104) ##STR00060##
and pharmaceutically acceptable salts, solvates, hydrates, tautomers, and stereoisomers thereof, wherein:

(105) R.sup.A1′ is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(106) R.sup.A1 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(Rb).sub.2, or —SR.sup.a;

(107) R.sup.A2′ is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group, or —CN;

(108) each instance of R.sup.A3 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(109) R.sup.A4 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;

(110) R.sup.A6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(111) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(112) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(113) c1 is 0, 1, 2, 3, 4, 5, or 6; and

(114) d1 is 0, 1, 2, 3, or 4.

(115) In one aspect of the present invention, provided are compounds of Formula (II):

(116) ##STR00061##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(117) R.sup.A1 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(118) R.sup.A2 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(119) each instance of R.sup.A3 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(120) R.sup.A4 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;

(121) R.sup.A5 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;

(122) R.sup.A6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(123) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(124) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(125) c is 1, 2, 3, 4, 5, or 6; and

(126) d is 1, 2, 3, or 4.

(127) In certain embodiments, a compound of Formula (II′) is of Formula (I-i).

(128) In one aspect of the present invention, provided are compounds of Formula (II-i):

(129) ##STR00062##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(130) R.sup.A8 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a; and

(131) e is 1 or 2.

(132) In certain embodiments, a compound of Formula (II′) is of Formula (II-ii).

(133) In one aspect of the present invention, provided are compounds of Formula (II-ii):

(134) ##STR00063##
or a pharmaceutically acceptable salt thereof, wherein:

(135) R.sup.A1 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(136) R.sup.A1′ is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(137) R.sup.A2 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(138) each instance of R.sup.A3 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(139) R.sup.A4 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;

(140) R.sup.A5 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;

(141) R.sup.A6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(142) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(143) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(144) c1 is 0, 1, 2, 3, 4, 5, or 6; and

(145) d1 is 0, 1, 2, 3, or 4.

(146) In one aspect of the resent invention, provided are compounds of Formula (IIA):

(147) ##STR00064##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(148) R.sup.A1 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(Rb).sub.2, or —SR.sup.a;

(149) R.sup.A2 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(150) each instance of R.sup.A3 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(151) R.sup.A6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(152) R.sup.B6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(153) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(154) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(155) c is 1, 2, 3, 4, 5, or 6; and

(156) d is 1, 2, 3, or 4.

(157) In certain embodiments, the compound of Formula (II′), (II), (II-i), (II-ii), or (IIA) is of the formula:

(158) ##STR00065##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(159) In certain embodiments, the compound of Formula (II′), (II), (II-i), and (IA) is of the formula:

(160) ##STR00066## ##STR00067## ##STR00068##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(161) In certain embodiments, the compound of Formula (II′), (II), (II-i), and (IA) is of the formula:

(162) ##STR00069##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(163) Compounds of Formulae (II′) include R.sup.A1′. In certain embodiments, R.sup.A1′ is hydrogen. In certain embodiments, R.sup.A1′ is halogen (e.g., F, Cl, Br, or I). In certain embodiments, R.sup.A1′ is —Br. In certain embodiments, R.sup.A1′ is —CN. In certain embodiments, R.sup.A1′ is —SCN. In certain embodiments, R.sup.A1′ is —NO.sub.2. In certain embodiments, R.sup.A1′ is —N.sub.3. In certain embodiments, R.sup.A1′ is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.A1′ is substituted methyl. In certain embodiments, R.sup.A1′ is unsubstituted methyl. In certain embodiments, R.sup.A1′ is substituted or unsubstituted ethyl. In certain embodiments, R.sup.A1′ is unsubstituted ethyl. In certain embodiments, R.sup.A1′ is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.A1′ is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.A1′ is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.A1′ is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.A1′ is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A1′ is an optionally substituted 5-membered heterocyclyl groups containing 3 heteroatoms. In certain embodiments, R.sup.A1′ is optionally substituted triazolinyl, oxadiazolinyl, or thiadiazolinyl. In certain embodiments, R.sup.A1′ is of the formula:

(164) ##STR00070##
wherein R.sup.B8 is optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted aryl, or optionally substituted heteroaryl. In certain embodiments, R.sup.B8 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.B8 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.B8 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.B8 is optionally substituted aryl. In certain embodiments, R.sup.B5 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A1′ is of the formula:

(165) ##STR00071##
In certain embodiments, R.sup.A1′ is an optionally substituted 6-membered heterocyclyl. In certain embodiments, R.sup.A1′ is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.A1′ is optionally substituted benzyl. In certain embodiments, R.sup.A1′ is optionally substituted phenyl. In certain embodiments, R.sup.A1′ is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A1′ is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, R.sup.A1′ is —OH. In certain embodiments, R.sup.A1′ is —OMe. In certain embodiments, R.sup.A1′ is —N(R.sup.b).sub.2 (e.g., —NMe.sub.2). In certain embodiments, R.sup.A1 is —NH.sub.2. In certain embodiments, R.sup.A1′ is —NHC(═O)(optionally substituted C.sub.1-6 alkyl). In certain embodiments, R.sup.A1′ is —NHC(═O)Me.

(166) In certain embodiments, R.sup.A1′ is of the of formula:

(167) ##STR00072##
wherein R.sup.z is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a; and z is 0, 1, 2, 3, 4, or 5. In certain embodiments, R.sup.A1′ is of the of formula:

(168) ##STR00073##
In certain embodiments, R.sup.A1′ is —NMe.sub.2. In certain embodiments, R.sup.A1′ is —SR.sup.a (e.g., —SMe). In certain embodiments, R.sup.A1′ is optionally substituted sulfonyl. In certain embodiments, R.sup.A1′ is halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a.

(169) Compounds of Formulae (II′), (II), (I-i), and (IIA) include R.sup.A1. In certain embodiments, R.sup.A1 is R.sup.A1′. In certain embodiments, each instance of R.sup.A1 is different. In certain embodiments, R.sup.A1 is hydrogen. In certain embodiments, RAI is halogen (e.g., F, Cl, Br, or I). In certain embodiments, R.sup.A1 is —Br. In certain embodiments, R.sup.A1 is —CN. In certain embodiments, R.sup.A1 is —SCN. In certain embodiments, R.sup.A1 is —NO.sub.2. In certain embodiments, R.sup.A1 is —N.sub.3. In certain embodiments, R.sup.A1 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.A1 is substituted methyl. In certain embodiments, R.sup.A1 is unsubstituted methyl. In certain embodiments, R.sup.A1 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.A1 is unsubstituted ethyl. In certain embodiments, R.sup.A1 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.A1 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.A1 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.A1 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.A1 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A1 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.A1 is optionally substituted benzyl. In certain embodiments, R.sup.A1 is optionally substituted phenyl. In certain embodiments, R.sup.A1 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A1 is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, R.sup.A1 is —OH. In certain embodiments, R.sup.A1 is —OMe. In certain embodiments, R.sup.A1 is —N(R.sup.b).sub.2 (e.g., —NMe.sub.2). In certain embodiments, R.sup.A1 is —NH.sub.2. In certain embodiments, R.sup.A1 is —NHC(═O)(optionally substituted C.sub.1-6 alkyl). In certain embodiments, R.sup.A1 is —NHC(═O)Me. In certain embodiments, RAI is —NMe.sub.2. In certain embodiments, R.sup.A1 is —SR.sup.a (e.g., —SMe). In certain embodiments, R.sup.A1 is optionally substituted sulfonyl. In certain embodiments, R.sup.A1 is halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(Rb).sub.2, or —SR.sup.a.

(170) Compounds of Formula (II′) include R.sup.A2′. In certain embodiments, R.sup.A2′ is hydrogen. In certain embodiments, R.sup.A2′ is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.A2′ is substituted methyl. In certain embodiments, R.sup.A2′ is unsubstituted methyl. In certain embodiments, R.sup.A2′ is substituted or unsubstituted ethyl. In certain embodiments, R.sup.A2′ is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.A2′ is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.A2′ is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.A2′ is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.A2′ is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A2′ is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.A2′ is optionally substituted benzyl. In certain embodiments, R.sup.A2′ is optionally substituted phenyl. In certain embodiments, R.sup.A2′ is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A2′ is a nitrogen protecting group. In certain embodiments, R.sup.A2′ is —CN. In certain embodiments, R.sup.A2 is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group, or —CN.

(171) Compounds of Formulae (II), (IIA), (VII), and (X) include R.sup.A2. In certain embodiments, R.sup.A2 is hydrogen. In certain embodiments, R.sup.A2 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6alkyl). In certain embodiments, R.sup.A2 is optionally substituted C.sub.1-6 alkyl. In certain embodiments, R.sup.A2 is of the formula: —(CH.sub.2).sub.xR.sup.A2b, wherein: x is 1, 2, 3, or 4; and R.sup.A2b is optionally substituted alkynyl, optionally substituted carbocyclyl, or optionally substituted aryl, or optionally substituted heteroaryl. In certain embodiments, R.sup.A1′ is of the formula:

(172) ##STR00074##
wherein R.sup.B8 is optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted aryl, or optionally substituted heteroaryl. In certain embodiments, R.sup.A2 is

(173) ##STR00075##
In certain embodiments, R.sup.A2 is substituted methyl. In certain embodiments, R.sup.A2 is unsubstituted methyl. In certain embodiments, R.sup.A2 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.A2 is n-butyl (n-Bu). In certain embodiments, R.sup.A2 is substituted or unsubstituted branched alkyl. In certain embodiments, R.sup.A2 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.A2 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.A2 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.A2 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.A2 is optionally substituted 3- to 7-membered, monocyclic carbocyclyl comprising zero double bonds in the carbocyclic ring system. In certain embodiments, R.sup.A2 is cyclopropyl. In certain embodiments, R.sup.A2 is cyclopropenyl. In certain embodiments, R.sup.A2 is cyclobutyl. In certain embodiments, R.sup.A2 is cyclopentyl. In certain embodiments, R.sup.A2 is cyclohexyl. In certain embodiments, R.sup.A2 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A2 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.A2 is optionally substituted benzyl. In certain embodiments, R.sup.A2 is unsubstituted benzyl. In certain embodiments, R.sup.A2 is substituted benzyl. In certain embodiments, R.sup.A2 is optionally substituted phenyl. In certain embodiments, R.sup.A2 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A2 is a nitrogen protecting group. In certain embodiments, R.sup.A2 is optionally substituted C.sub.1-6 alkyl, optionally substituted alkynyl, optionally substituted carbocycle or optionally substituted aryl. In certain embodiments, R.sup.A2 is of the formula:

(174) ##STR00076##
In certain embodiments, R.sup.A2 is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group.

(175) Compounds of Formulae (II′), (II), (IIA), (IIA), (III″), (IIIA), (VIII′), (VIII), (IX′), (IX), and (X) include one or more instances of R.sup.3. In certain embodiments, c is 1. In certain embodiments, c is 2. In certain embodiments, c is 3. In certain embodiments, c is 4. In certain embodiments, c is 5. In certain embodiments, c is 6. In certain embodiments, c is c. In certain embodiments, c1 is 0. In certain embodiments, c1 is 2. In certain embodiments, c1 is 3. In certain embodiments, c1 is 4. In certain embodiments, c1 is 5. In certain embodiments, c1 is 6. In certain embodiments, at least one instance of R.sup.A3 is hydrogen. In certain embodiments, there is one instance of each of R.sup.A3, R.sup.A6, and R.sup.D6. In certain embodiments, at least one instance of R.sup.A3 is hydrogen, at least one instance of R.sup.A6 is hydrogen, and at least one instance of R.sup.D6 is hydrogen. In certain embodiments, there is one instance of each of R.sup.A3 and R.sup.A6. In certain embodiments, at least one instance of R.sup.A3 is hydrogen and at least one instance of R.sup.A6 is hydrogen. In certain embodiments, at least one instance of R.sup.A3 is halogen (e.g., F, Cl, Br, or I). In certain embodiments, at least one instance of R.sup.A3 is —CN. In certain embodiments, at least one instance of R.sup.A3 is —SCN. In certain embodiments, at least one instance of R.sup.A3 is —NO.sub.2. In certain embodiments, at least one instance of R.sup.A3 is —N.sub.3. In certain embodiments, at least one instance of R.sup.A3 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, at least one instance of R′ is substituted methyl. In certain embodiments, at least one instance of R.sup.A3 is unsubstituted methyl. In certain embodiments, at least one instance of R.sup.A3 is substituted or unsubstituted ethyl. In certain embodiments, at least one instance of R.sup.A3 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, at least one instance of R.sup.A3 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, at least one instance of R.sup.A3 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, at least one instance of R.sup.A3 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, at least one instance of R.sup.A3 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R.sup.A3 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, at least one instance of R.sup.A3 is optionally substituted benzyl. In certain embodiments, at least one instance of R.sup.A3 is optionally substituted phenyl. In certain embodiments, at least one instance of R.sup.A3 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R.sup.A3 is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, at least one instance of R.sup.A3 is —OH. In certain embodiments, at least one instance of R.sup.A3 is —OMe. In certain embodiments, at least one instance of R.sup.A3 is —N(R.sup.b).sub.2 (e.g., —NMe.sub.2). In certain embodiments, at least one instance of R.sup.A3 is —NMe.sub.2. In certain embodiments, at least one instance of R.sup.A3 is —SR.sup.a (e.g., —SMe). In certain embodiments, at least one instance of R′ is optionally substituted sulfonyl. In certain embodiments, at least one instance of R.sup.A3 is halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a.

(176) Compounds of Formulae (II′), (II), (II-i), and (X) include R.sup.A4. In certain embodiments, R.sup.A4 is hydrogen. In certain embodiments, R.sup.A4 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6alkyl). In certain embodiments, R.sup.A4 is substituted methyl. In certain embodiments, R.sup.A4 is unsubstituted methyl. In certain embodiments, R.sup.A4 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.A4 is unsubstituted ethyl. In certain embodiments, R.sup.A4 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.A4 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.A4 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.A4 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.A4 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A4 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.A4 is optionally substituted benzyl. In certain embodiments, R.sup.A4 is optionally substituted phenyl. In certain embodiments, R.sup.A4 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A4 is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl.

(177) Compounds of Formulae (II), (II-i), and (X) include R.sup.A5. In certain embodiments, R.sup.A5 is hydrogen. In certain embodiments, R.sup.A5 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, RM is substituted methyl. In certain embodiments, R.sup.A5 is unsubstituted methyl. In certain embodiments, R.sup.A5 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.A5 is unsubstituted ethyl. In certain embodiments, R.sup.A5 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.A5 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.A5 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.A5 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.A5 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A5 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.A5 is optionally substituted benzyl. In certain embodiments, RM is optionally substituted phenyl. In certain embodiments, R.sup.A5 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A5 is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl.

(178) Compounds of Formulae (II′), (II), (IIA), (III″), (IIIA), (VIII′), (VIII), (IX′), (IX), and (X) include one or more instances of R.sup.A6. In certain embodiments, d is 1. In certain embodiments, d is 2. In certain embodiments, d is 3. In certain embodiments, d is 4. In certain embodiments, d is d1. In certain embodiments, d1 is 0. In certain embodiments, d1 is 1. In certain embodiments, d1 is 2. In certain embodiments, d1 is 3. In certain embodiments, d1 is 4.

(179) In certain embodiments, at least one instance of R.sup.A6 is hydrogen. In certain embodiments, at least one instance of R.sup.A6 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, at least one instance of R.sup.A6 is substituted methyl. In certain embodiments, at least one instance of R.sup.A6 is unsubstituted methyl. In certain embodiments, at least one instance of R.sup.A6 is substituted or unsubstituted ethyl. In certain embodiments, at least one instance of R.sup.A6 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, at least one instance of R.sup.A6 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, at least one instance of R.sup.A6 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, at least one instance of R.sup.A6 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, at least one instance of R.sup.A6 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R.sup.A6 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, at least one instance of R.sup.A6 is optionally substituted benzyl. In certain embodiments, at least one instance of R.sup.A6 is optionally substituted phenyl. In certain embodiments, at least one instance of R.sup.A6 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R.sup.A6 is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group.

(180) Formula (II-i) includes one or more instances of R.sup.A8. In certain embodiments, e is 1. In certain embodiments, e is 2. In certain embodiments, e is e1. In certain embodiments, e1 is 0. In certain embodiments, e1 is 1. In certain embodiments, e1 is 2. In certain embodiments, R.sup.A8 is R.sup.B8. In certain embodiments, R.sup.B8 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a. In certain embodiments, R.sup.B8 is halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a.

(181) Compounds of Formulae (IIA), (III′), (III″), (IIIA), (VII), (IX′), and (IX) include R.sup.B6. In certain embodiments, R.sup.B6 is hydrogen. In certain embodiments, R.sup.B6 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.B6 is substituted methyl. In certain embodiments, R.sup.B6 is unsubstituted methyl. In certain embodiments, R.sup.B6 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.B6 is unsubstituted ethyl. In certain embodiments, R.sup.B6 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.B6 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.B6 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.B6 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.B6 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.B6 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.B6 is optionally substituted benzyl. In certain embodiments, R.sup.B6 is optionally substituted phenyl. In certain embodiments, R.sup.B6 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.B6 is a nitrogen protecting group. In certain embodiments, R.sup.B6 is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group. In certain embodiments, R.sup.B6 is R.sup.B6′. In certain embodiments, R.sup.B6′ is —CN.

(182) In one aspect of the present invention, provided are compounds of Formula (III″):

(183) ##STR00077##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(184) R.sup.A6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(185) each instance of R.sup.A3a is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, —SR.sup.a, or optionally two instances of R.sup.A3a are taken together with their intervening atoms to form an optionally substituted carbocyclic ring or optionally substituted heterocyclic ring;

(186) R.sup.B4 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(187) R.sup.B5 is —OR.sup.a or —N(R.sup.b).sub.2;

(188) R.sup.B6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(189) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(190) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(191) c1 is 0, 1, 2, 3, 4, 5, or 6; and

(192) d1 is 0, 1, 2, 3, or 4.

(193) In one aspect of the present invention, provided are compounds of Formula (III′):

(194) ##STR00078##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(195) R.sup.A6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(196) each instance of R.sup.A3a is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, —SR.sup.a, or optionally two instances of R.sup.A3a are taken together with their intervening atoms to form an optionally substituted carbocyclic ring or optionally substituted heterocyclic ring;

(197) R.sup.B4 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(198) R.sup.B5 is —OR.sup.a or —N(R.sup.b).sub.2;

(199) R.sup.B6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(200) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(201) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(202) c is 1, 2, 3, 4, 5, or 6; and

(203) d is 1, 2, 3, or 4.

(204) In certain embodiments, a compound of Formula (III″) is of Formula (III).

(205) In one aspect of the present invention, provided are compounds of Formula (III):

(206) ##STR00079##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(207) R.sup.B4 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(208) R.sup.B5 is —OR.sup.a or —N(R.sup.b).sub.2;

(209) R.sup.B6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(210) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(211) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl.

(212) In one aspect of the present invention, provided are compounds of Formula (IIIA):

(213) ##STR00080##

(214) or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(215) each instance of R.sup.A3 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(216) R.sup.A6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(217) R.sup.B4 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(218) R.sup.B5 is —OR.sup.a or —N(R.sup.b).sub.2;

(219) R.sup.B6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(220) R.sup.B7 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(221) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(222) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(223) c is 1, 2, 3, 4, 5, or 6; and

(224) d is 1, 2, 3, or 4.

(225) In certain embodiments, the compound of Formula (III″), (III′), (III), and (IIIA) is of the formula:

(226) ##STR00081##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(227) In certain embodiments, the compound of Formula (III″), (III′), (III), and (IIIA) is of the formula:

(228) ##STR00082## ##STR00083##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(229) In certain embodiments, the compound of Formula (III″), (III′), (III), and (IIIA) is of the formula:

(230) ##STR00084##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(231) Compounds of Formula (III″) and (III′) include one or more instances of RA. In certain embodiments, c is 1. In certain embodiments, c is 2. In certain embodiments, c is 3. In certain embodiments, c is 4. In certain embodiments, c is 5. In certain embodiments, c is 6. In certain embodiments, at least one instance of R.sup.A3a is halogen (e.g., F, Cl, Br, or I). In certain embodiments, at least one instance of R.sup.A3a is —CN. In certain embodiments, at least one instance of R.sup.A3a is —SCN. In certain embodiments, at least one instance of R.sup.A3a is —NO.sub.2. In certain embodiments, at least one instance of R.sup.A3a is —N.sub.3. In certain embodiments, at least one instance of R.sup.A3a is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, at least one instance of R.sup.A3a is substituted methyl. In certain embodiments, at least one instance of R.sup.A3a is unsubstituted methyl. In certain embodiments, at least one instance of R.sup.A3a is substituted or unsubstituted ethyl. In certain embodiments, at least one instance of R.sup.A3a is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, at least one instance of R.sup.A3a is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, at least one instance of R.sup.A3a is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, at least one instance of R.sup.A3a is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, at least one instance of R.sup.A3a is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R.sup.A3a is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, at least one instance of R.sup.A3a is optionally substituted benzyl. In certain embodiments, at least one instance of R.sup.A3a is optionally substituted phenyl. In certain embodiments, at least one instance of R.sup.A3a is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R.sup.A3a is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, at least one instance of R.sup.A3a is —OH. In certain embodiments, at least one instance of R.sup.A3a is —OMe. In certain embodiments, at least one instance of R.sup.A3a is —N(R.sup.b).sub.2 (e.g., —NMe.sub.2). In certain embodiments, at least one instance of R.sup.A3a is —NMe.sub.2. In certain embodiments, at least one instance of R.sup.A3a is —SR.sup.a (e.g., —SMe). In certain embodiments, at least one instance of R.sup.A3a is sulfonyl. In certain embodiments, two instances of R.sup.A3a are taken together with their intervening atoms to form an optionally substituted carbocyclic ring (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, two instances of R.sup.A3a are taken together with their intervening atoms to form an optionally substituted heterocyclic ring (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R.sup.A3a is optionally halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, —SR.sup.a, or optionally two instances of R.sup.A3a are taken together with their intervening atoms to form an optionally substituted carbocyclic ring or optionally substituted heterocyclic ring.

(232) Compounds of Formula (III″), (III′), (III), and (IIIA) include R.sup.B4. In certain embodiments, R.sup.B4 is hydrogen. In certain embodiments, R.sup.B4 is halogen (e.g., F, Cl, Br, or I). In certain embodiments, R.sup.B4 is —Br. In certain embodiments, R.sup.B4 is —CN. In certain embodiments, R.sup.B4 is —SCN. In certain embodiments, R.sup.B4 is —NO.sub.2. In certain embodiments, R.sup.B4 is —N.sub.3. In certain embodiments, R.sup.B4 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.B4 is substituted methyl. In certain embodiments, R.sup.B4 is unsubstituted methyl. In certain embodiments, R.sup.B4 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.B4 is unsubstituted ethyl. In certain embodiments, R.sup.B4 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.B4 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.B4 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.B4 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.B4 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.B4 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.B4 is optionally substituted benzyl. In certain embodiments, R.sup.B4 is optionally substituted phenyl. In certain embodiments, R.sup.B4 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.B4 is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, R.sup.B4 is —OH. In certain embodiments, R.sup.B4 is —OMe. In certain embodiments, R.sup.B4 is —N(R.sup.b).sub.2 (e.g., —NMe.sub.2). In certain embodiments, R.sup.B4 is —NH.sub.2. In certain embodiments, R.sup.B4 is —NHC(═O)(optionally substituted C.sub.1-6 alkyl). In certain embodiments, R.sup.B4 is —NHC(═O)Me. In certain embodiments, R.sup.A1 is —NMe.sub.2. In certain embodiments, R.sup.B4 is —SR.sup.a (e.g., —SMe). In certain embodiments, R.sup.B4 is optionally substituted sulfonyl. In certain embodiments, R.sup.B4 is halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a.

(233) Compounds of Formula (III″), (III′), (III), and (IIIA) include R.sup.B5. In certain embodiments, R.sup.B5 is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, R.sup.B5 is —OR.sup.a, wherein: R.sup.a is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted phenyl. In certain embodiments, R.sup.B5 is —OH, —OMe, —OBn, or of the formula:

(234) ##STR00085##
In certain embodiments, R.sup.B5 is —O(optionally substituted alkyl) or —NH(optionally substituted aryl). In certain embodiments, R.sup.B5 is —O(optionally substituted alkyl). In certain embodiments, R.sup.B5 is —O(optionally substituted C.sub.1-6 alkyl). In certain embodiments, R.sup.B5 is —OMe. In certain embodiments, R.sup.B5 is —OEt. In certain embodiments, R.sup.B5 is —NH(optionally substituted aryl).

(235) In certain embodiments, R.sup.B5 is —N(R.sup.b).sub.2. In certain embodiments, R.sup.B5 is —N(R.sup.b).sub.2, wherein each instance of R.sup.b is independently hydrogen, optionally substituted alkyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted phenyl, or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl. In certain embodiments R.sup.B5 is —NH(nBu). In certain embodiments, R.sup.B5 is —N(nBu).sub.2. In certain embodiments, R.sup.B5 is

(236) ##STR00086##
In certain embodiments, R.sup.B5 is

(237) ##STR00087##
In certain embodiments, R.sup.B5 is

(238) ##STR00088##
In certain embodiments, R.sup.B5 is of the formula:

(239) ##STR00089##
wherein R.sup.z is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a; and z is 0, 1, 2, 3, 4, or 5. In certain embodiments, z is 0. In certain embodiments, z is 1. In certain embodiments, z is 2. In certain embodiments, z is 3. In certain embodiments, z is 4. In certain embodiments, z is 5. In certain embodiments, R.sup.B5 is of the formula:

(240) ##STR00090##
In certain embodiments, R.sup.B5 is —N(R.sup.b).sub.2, wherein two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl. In certain embodiments, R.sup.B5 is

(241) ##STR00091##
In certain embodiments, R.sup.B5 is —OR.sup.a or —N(R.sup.b).sub.2, wherein: R.sup.a is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted phenyl; and each instance of R.sup.b is independently hydrogen, optionally substituted alkyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted phenyl, or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl.

(242) In one aspect of the present invention, provided are compounds of Formula (IV):

(243) ##STR00092##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(244) R.sup.C1 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(245) each instance of R.sup.2 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(246) R.sup.C3 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(247) R.sup.C4 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(248) R.sup.C5 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(249) R.sup.C6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(250) each instance of R.sup.C7 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(251) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(252) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(253) f is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and

(254) g is 1, 2, 3, or 4.

(255) In certain embodiments, the compound of Formula (IV) is of the formula:

(256) ##STR00093##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(257) In certain embodiments, the compound of Formula (IV) is of the formula:

(258) ##STR00094##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(259) Compounds of Formula (IV) include R.sup.C1. In certain embodiments, R.sup.C1 is hydrogen. In certain embodiments, R.sup.C1 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.C1 is substituted methyl. In certain embodiments, R.sup.C1 is unsubstituted methyl. In certain embodiments, R.sup.C1 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.C1 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.C1 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.C1 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.C1 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.C1 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.C1 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.C1 is optionally substituted benzyl. In certain embodiments, R.sup.C1 is optionally substituted phenyl. In certain embodiments, R.sup.C1 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.C1 is a nitrogen protecting group. In certain embodiments, R.sup.C1 is R.sup.C1′. In certain embodiments, R.sup.C1′ is —CN.

(260) Compounds of Formula (IV) include one or more instances of R.sup.C2. In certain embodiments, f is 1. In certain embodiments, f is 2. In certain embodiments, f is 3. In certain embodiments, f is 4. In certain embodiments, f is 5. In certain embodiments, f is 6. In certain embodiments, f is 7. In certain embodiments, f is 8. In certain embodiments, f is 9. In certain embodiments, f is 10.

(261) In certain embodiments, f is f1. In certain embodiments, f1 is 0. In certain embodiments, f1 is 1. In certain embodiments, f1 is 2. In certain embodiments, f1 is 3. In certain embodiments, f1 is 4. In certain embodiments, f1 is 5. In certain embodiments, f1 is 6. In certain embodiments, f1 is 7. In certain embodiments, f1 is 8. In certain embodiments, f1 is 9. In certain embodiments, f1 is 10.

(262) In certain embodiments, at least one instance of R.sup.C2 is hydrogen. In certain embodiments, at least one instance of R.sup.C2 is halogen (e.g., F, Cl, Br, or I). In certain embodiments, at least one instance of R.sup.C2 is —CN. In certain embodiments, at least one instance of R.sup.C2 is —SCN. In certain embodiments, at least one instance of R.sup.C2 is —NO.sub.2. In certain embodiments, at least one instance of R.sup.C2 is —N.sub.3. In certain embodiments, at least one instance of R.sup.C2 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, at least one instance of R.sup.C2 is substituted methyl. In certain embodiments, at least one instance of R.sup.C2 is unsubstituted methyl. In certain embodiments, at least one instance of R.sup.C2 is substituted or unsubstituted ethyl. In certain embodiments, at least one instance of R.sup.C2 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, at least one instance of R.sup.C2 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, at least one instance of R.sup.C2 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, at least one instance of R.sup.C2 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, at least one instance of R.sup.C2 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R.sup.C2 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, at least one instance of R.sup.C2 is optionally substituted benzyl. In certain embodiments, at least one instance of R.sup.C2 is optionally substituted phenyl. In certain embodiments, at least one instance of R.sup.C2 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, at least one instance of R.sup.C2 is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, at least one instance of R.sup.C2 is —OH. In certain embodiments, at least one instance of R R.sup.C2 A3 is —OMe. In certain embodiments, at least one instance of R.sup.C2 is —N(R.sup.b).sub.2 (e.g., —NMe.sub.2). In certain embodiments, at least one instance of R.sup.C2 is —NMe.sub.2. In certain embodiments, at least one instance of R.sup.C2 is —SR.sup.a (e.g., —SMe). In certain embodiments, at least one instance of R.sup.C2 is optionally substituted sulfonyl. In certain embodiments, at least one instance of R.sup.C2 is halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a.

(263) Compounds of Formula (IV) include R.sup.C3. In certain embodiments, R.sup.C3 is hydrogen. In certain embodiments, R.sup.C3 is halogen (e.g., F, Cl, Br, or I). In certain embodiments, R.sup.C3 is —CN. In certain embodiments, R.sup.3 is —SCN. In certain embodiments, R.sup.C3 is —NO.sub.2. In certain embodiments, R.sup.C3 is —N.sub.3. In certain embodiments, R.sup.C3 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.C3 is optionally substituted C.sub.1-6 alkyl. In certain embodiments, R.sup.3 is substituted methyl. In certain embodiments, R.sup.C3 is unsubstituted methyl. In certain embodiments, R.sup.C3 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.C3 is unsubstituted ethyl. In certain embodiments, R.sup.C3 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.C3 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.C3 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.C3 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.C3 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.C3 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.C3 is optionally substituted benzyl. In certain embodiments, R.sup.C3 is optionally substituted phenyl. In certain embodiments, R.sup.C3 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.C3 is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, R.sup.C3 is —OH. In certain embodiments, R.sup.C3 is —OMe. In certain embodiments, R.sup.C3 is —N(R.sup.b).sub.2 (e.g., —NMe.sub.2). In certain embodiments, R.sup.C3 is —NMe.sub.2. In certain embodiments, R.sup.C3 is —SR.sup.a (e.g., —SMe). In certain embodiments, R.sup.C3 is optionally substituted sulfonyl.

(264) Compounds of Formula (IV) include R.sup.C4. In certain embodiments, R.sup.C4 is hydrogen. In certain embodiments, R.sup.C4 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.C4 is optionally substituted C.sub.1-6 alkyl. In certain embodiments, R.sup.C4 is substituted methyl. In certain embodiments, R.sup.C4 is unsubstituted methyl. In certain embodiments, R.sup.C4 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.C4 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.C4 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.C4 is optionally substituted C.sub.1-6 alkyl or optionally substituted alkenyl. In certain embodiments, R.sup.C4 is of the formula

(265) ##STR00095##
In certain embodiments, R.sup.C4 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.C4 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.C4 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.C4 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.C4 is optionally substituted benzyl. In certain embodiments, R.sup.C4 is optionally substituted phenyl. In certain embodiments, R.sup.C4 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.C4 is an oxygen protecting group.

(266) Compounds of Formula (IV) include R.sup.C5. In certain embodiments, R.sup.C5 is hydrogen. In certain embodiments, R.sup.C5 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.C5 is optionally substituted C.sub.1-6 alkyl. In certain embodiments, R.sup.C5 is substituted methyl. In certain embodiments, R.sup.C5 is unsubstituted methyl. In certain embodiments, R.sup.C5 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.C5 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.C5 is optionally substituted alkenyl (e, substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.C5 is of the formula

(267) ##STR00096##
In certain embodiments, R.sup.C5 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.C5 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.C5 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.C5 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.C5 is optionally substituted benzyl. In certain embodiments, R.sup.C5 is of the formula:

(268) ##STR00097##
wherein R.sup.z is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a; and z is 0, 1, 2, 3, 4, or 5. In certain embodiments, R.sup.z is halogen (e.g., F, Cl, Br, or I). In certain embodiments, R.sup.z is optionally substituted C.sub.1-6 alkyl. In certain embodiments, R.sup.C5 is of the formula:

(269) ##STR00098##
In certain embodiments, R.sup.C5 is optionally substituted phenyl. In certain embodiments, R.sup.C5 is optionally substituted C.sub.1-6 alkyl or optionally substituted aryl. In certain embodiments, R.sup.C5 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.C5 is an oxygen protecting group. In certain embodiments, R.sup.C5 is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group.

(270) Compounds of Formula (IV) include R.sup.C6. In certain embodiments, R.sup.C6 is hydrogen. In certain embodiments, R.sup.C6 is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(271) Compounds of Formula (IV) include one or more instances of R.sup.7. In certain embodiments, g is 1. In certain embodiments, g is 2. In certain embodiments, g is 3. In certain embodiments, g is 4.

(272) In certain embodiments, g is g1. In certain embodiments, g1 is 0. In certain embodiments, g1 is 1. In certain embodiments, g1 is 2. In certain embodiments, g1 is 3. In certain embodiments, g1 is 4.

(273) In one aspect of the present invention, provided are compounds of Formula (V′):

(274) ##STR00099##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(275) each instance of independently indicates a single or double bond;

(276) R.sup.D1′ is hydrogen, halogen, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, or optionally substituted aryl;

(277) R.sup.D3 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(278) R.sup.D4′ is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —C(═O)OR.sup.D4, —N(R.sup.b).sub.2, or —SR.sup.a;

(279) R.sup.D1 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or optionally, R.sup.D4′ and R.sup.D are joined together to form ═O;

(280) each instance of R.sup.D4a and R.sup.D4b is independently independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a, or optionally, R.sup.D4a and R.sup.D4b are joined together with the intervening atoms to form optionally substituted heterocyclyl;

(281) each instance of R.sup.D5 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(282) each instance of R.sup.D6 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(283) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(284) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(285) j1 is 0, 1, 2, 3, or 4; and

(286) k1 is 0, 1, 2, 3, or 4.

(287) In certain embodiments, a compound of Formula (V′) is of Formula (V).

(288) In one aspect of the present invention, provided are compounds of Formula (V):

(289) ##STR00100##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(290) R.sup.D1 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(291) each instance of R.sup.D2 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(292) R.sup.D3 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(293) R.sup.D4 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;

(294) each instance of R.sup.D5 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(295) each instance of R.sup.L is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(296) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(297) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(298) h is 1, 2, 3, or 4;

(299) j is 1, 2, 3, or 4; and

(300) k is 1, 2, 3, or 4.

(301) In certain embodiments, a compound of Formula (V′) is of formula:

(302) ##STR00101##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(303) In certain embodiments, a compound of Formula (V′) is of formula:

(304) ##STR00102##

(305) or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof,

(306) R.sup.D1 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(307) each instance of R.sup.D2 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a; and

(308) h is 1, 2, 3, or 4.

(309) In certain embodiments, the compound of Formulae (V′) or (V) is of the formula:

(310) ##STR00103## ##STR00104##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(311) Compounds of Formula (V′) include R.sup.D1′. In certain embodiments, R.sup.D1′ is hydrogen. In certain embodiments, R.sup.D1′ is halogen (e.g., F, Cl, Br, or I). In certain embodiments, R.sup.D1′ is I. In certain embodiments, R.sup.D1′ is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.D1′ is optionally substituted C.sub.1-6 alkyl. In certain embodiments, R.sup.D1′ is substituted methyl. In certain embodiments, R.sup.D1′ is unsubstituted methyl. In certain embodiments, R.sup.D1′ is substituted or unsubstituted ethyl. In certain embodiments, R.sup.D1′ is unsubstituted ethyl. In certain embodiments, R.sup.D1′ is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.D1′ is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.D1′ is substituted or unsubstituted C.sub.2-6 alkenyl. In certain embodiments, R.sup.D1′ is of formula:

(312) ##STR00105##
In certain embodiments, R.sup.D1′ is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.D1′ is optionally substituted C.sub.2-6 alkynyl. In certain embodiments R.sup.D1′ is of formula:

(313) ##STR00106##
In certain embodiments, R.sup.D1′ is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.D1′ is optionally substituted benzyl. In certain embodiments, R.sup.D1′ is optionally substituted phenyl. In certain embodiments, R.sup.D1′ is of the formula:

(314) ##STR00107##
wherein: each instance of R.sup.D2 is independently —OR.sup.a or optionally substituted heterocyclyl, and h1 is 0, 1, 2, 3, 4, or 5. In certain embodiments, h1 is h. In certain embodiments, R.sup.D1′ is of the formula:

(315) ##STR00108##

(316) Each instance of independently indicates a single or double bond. In certain embodiments, is a single bond. In certain embodiments, is a double bond.

(317) Compounds of Formula (V) include one or more instances of R.sup.D2. In certain embodiments, h is 1, 2, 3, or 4. In certain embodiments, h is 1. In certain embodiments, h is 2. In certain embodiments h is 3. In certain embodiments, h is 4. In certain embodiments, h is h1. In certain embodiments, h1 is 0. In certain embodiments, h is 1. In certain embodiments, h1 is 2. In certain embodiments, hi is 3. In certain embodiments, hi is 4. In certain embodiments, at least one instance of R.sup.D2 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a. In certain embodiments, at least one instance of R.sup.D2 is independently halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a.

(318) Compounds of Formulae (V′) and (V) include R.sup.D3. In certain embodiments, R.sup.D3 is hydrogen. In certain embodiments, R.sup.D3 is halogen (e.g., F, Cl, Br, or I). In certain embodiments, R.sup.D3 is —CN. In certain embodiments, R.sup.D3 is —SCN. In certain embodiments, R.sup.D3 is —NO.sub.2. In certain embodiments, R.sup.D3 is —N.sub.3. In certain embodiments, R.sup.D3 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.D3 is substituted methyl. In certain embodiments, R.sup.D3 is unsubstituted methyl. In certain embodiments, R.sup.D3 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.D3 is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.D3 is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.D3 is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.D3 is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.D3 is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.D3 is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.D3 is optionally substituted benzyl. In certain embodiments, R.sup.D3 is optionally substituted phenyl. In certain embodiments, R.sup.D3 is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.D3 is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, R.sup.D3 is —OH. In certain embodiments, R.sup.D3 is —OMe. In certain embodiments, R.sup.D3 is —N(R.sup.b).sub.2 (e.g., —NMe.sub.2). In certain embodiments, R.sup.D3 is —NMe.sub.2. In certain embodiments, R.sup.D3 is —SR.sup.a (e.g., —SMe). In certain embodiments, R.sup.D3 is optionally substituted sulfonyl.

(319) Compounds of Formulae (V′) include R.sup.D4′. In certain embodiments, R.sup.D4′ is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —C(═O)OR.sup.D4, —N(R.sup.b).sub.2, or —SR.sup.a.

(320) Compounds of Formulae (V′) and (V) include R.sup.D4. In certain embodiments, R.sup.D4 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl. In certain embodiments, R.sup.D4′ and R.sup.D4 are joined together to form ═O. In certain embodiments, R.sup.D4 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.D4 is substituted methyl. In certain embodiments, R.sup.D4 is unsubstituted methyl. In certain embodiments, R.sup.D4 is substituted or unsubstituted ethyl.

(321) In certain embodiments, each instance of R.sup.D4a and R.sup.D4b is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a. In certain embodiments, R.sup.D4a and R.sup.D4b are joined together with the intervening atoms to form optionally substituted heterocyclyl. In certain embodiments, R.sup.D4a and R.sup.D4b are joined together with the intervening atoms to form an optionally substituted, 5- to 10-membered monocyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur. In certain embodiments, R.sup.D4a and R.sup.D4b are joined together with the intervening atoms to form an unsubstituted heterocyclyl with a bridging oxygen atom. In certain embodiments, R.sup.D4a and R.sup.D4b are joined together with the intervening atoms to form tetrahydrofuran.

(322) Compounds of Formulae (V′), (V), and (VII) include one or more instances of R.sup.D5. In certain embodiments, j is 1. In certain embodiments, j is 2. In certain embodiments, j is 3. In certain embodiments, j is 4. In certain embodiments, j is j1. In certain embodiments, j1 is 0. In certain embodiments, j1 is 1. In certain embodiments, j is 2. In certain embodiments, j1 is 3. In certain embodiments, j1 is 4. In certain embodiments, at least one instance of R.sup.D5 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a.

(323) Compounds of Formulae (V′), (V), (VII), (VIII′), (VIII), and (IX) include one or more instances of R.sup.D6. In certain embodiments, k is 1. In certain embodiments, k is 2. In certain embodiments, k is 3. In certain embodiments, k is 4. In certain embodiments, k is k1. In certain embodiments, k1 is 0. In certain embodiments, k1 is 1. In certain embodiments, k1 is 2. In certain embodiments, k1 is 3. In certain embodiments, k1 is 4.

(324) In certain embodiments, q is 1. In certain embodiments, q is 2. In certain embodiments, q is 3. In certain embodiments, q is 4.

(325) In certain embodiments, q is q1. In certain embodiments, q1 is 0. In certain embodiments, q1 is 1. In certain embodiments, q1 is 2. In certain embodiments, q1 is 3. In certain embodiments, q1 is 4.

(326) In certain embodiments, at least one instance of R.sup.D6 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a. In certain embodiments, j is 1 and k is 1. In certain embodiments, R.sup.D5 and R.sup.D6 are both hydrogen. In certain embodiments, c is 1, d is 1, and q is 1. In certain embodiments, R.sup.A3 is hydrogen, R.sup.A6 is hydrogen, and R.sup.D6 is hydrogen.

(327) In certain embodiments, c1 is 0, d1 is 0, and q1 is 0.

(328) In one aspect of the present invention, provided are compounds of Formula (VI):

(329) ##STR00109##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(330) each instance of R.sup.E1 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(331) each instance of R.sup.E2 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(332) R.sup.E3 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(333) R.sup.E4 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;

(334) R.sup.E5 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(335) each instance of R.sup.E6 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(336) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(337) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(338) m is 1, 2, 3, or 4;

(339) n is 1, 2, 3, 4, 5, or 6; and

(340) p is 1, 2, 3, or 4.

(341) In certain embodiments, the compound of Formula (VI) is of the formula:

(342) ##STR00110##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(343) In certain embodiments, the compound of Formula (VI) is of the formula:

(344) ##STR00111##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(345) Compounds of Formula (VI) include one or more instances of R.sup.E1. In certain embodiments, m is 1. In certain embodiments, m is 2. In certain embodiments, m is 3. In certain embodiments, m is 4.

(346) In certain embodiments, m is m1. In certain embodiments, m1 is 0. In certain embodiments, m1 is 2. In certain embodiments, m1 is 3. In certain embodiments, m1 is 4.

(347) In certain embodiments, at least one instance of R.sup.E1 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a. In certain embodiments, at least one instance of R.sup.E1 is hydrogen.

(348) Compounds of Formula (VI) and (X) include one or more instances of R.sup.E2. In certain embodiments, n is 1. In certain embodiments, n is 2. In certain embodiments, n is 3. In certain embodiments, n is 4. In certain embodiments, n is 5. In certain embodiments, n is 6.

(349) In certain embodiments, n is n1. In certain embodiments, n1 is 0. In certain embodiments, n1 is 1. In certain embodiments, n1 is 2. In certain embodiments, n1 is 3. In certain embodiments, n1 is 4. In certain embodiments, n1 is 5. In certain embodiments, n1 is 6. In certain embodiments, p is p1. In certain embodiments, p1 is 0. In certain embodiments, p1 is 1. In certain embodiments, p1 is 2. In certain embodiments, p1 is 3. In certain embodiments, p is 4. In certain embodiments, e is 0, d1 is 0, and p1 is 0.

(350) In certain embodiments, p is 1. In certain embodiments, p is 2. In certain embodiments, p is 3. In certain embodiments, p is 4. In certain embodiments, m is 1, n is 1, and p is 1. In certain embodiments, c is 1, d is 1, and p is 1. In certain embodiments, R.sup.A3 is hydrogen, R.sup.A6 is hydrogen, and R.sup.E2 is hydrogen. In certain embodiments, at least one instance of R.sup.E2 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a. In certain embodiments, at least one instance of R.sup.E2 is hydrogen.

(351) Compounds of Formula (VI) include R.sup.E3. In certain embodiments, R.sup.E3 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a. In certain embodiments, R.sup.E3 is hydrogen. In certain embodiments, R.sup.E3 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.E3 is substituted methyl. In certain embodiments, R.sup.E3 is unsubstituted methyl. In certain embodiments, R.sup.E3 is substituted or unsubstituted ethyl.

(352) Compounds of Formula (VI) include R.sup.E4. In certain embodiments, R.sup.E4 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl. In certain embodiments, R.sup.E4 is hydrogen. In certain embodiments, R.sup.E4 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.E4 is substituted methyl. In certain embodiments, R.sup.E4 is unsubstituted methyl. In certain embodiments, R.sup.E4 is substituted or unsubstituted ethyl.

(353) Compounds of Formula (VI) include R.sup.E5. In certain embodiments, R.sup.E5 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group. In certain embodiments, R.sup.E5 is hydrogen. In certain embodiments, R.sup.E5 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.E5 is substituted methyl. In certain embodiments, R.sup.E5 is unsubstituted methyl. In certain embodiments, R.sup.E5 is substituted or unsubstituted ethyl.

(354) Compounds of Formula (VI) include one or more instances of R.sup.E6. In certain embodiments, p is 1. In certain embodiments, p is 2. In certain embodiments, p is 3. In certain embodiments, p is 4. In certain embodiments, at least one instance of R.sup.E6 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a. In certain embodiments, at least one instance of R.sup.E6 is hydrogen. In certain embodiments, m is 1, n is 1, and p is 1. In certain embodiments, ml is 0, n1 is 0, and p1 is 0.

(355) In one aspect of the present invention, provided are compounds of Formula (VII):

(356) ##STR00112##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(357) R.sup.A2 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(358) R.sup.B6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(359) each instance of R.sup.D5 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(360) each instance of R.sup.D6 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(361) R.sup.F1 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(362) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(363) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(364) j is 1, 2, 3, or 4; and

(365) k is 1, 2, 3, or 4.

(366) In certain embodiments, the compound of Formula (VII) is of the formula:

(367) ##STR00113##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(368) In certain embodiments, the compound of Formula (VII) is of the formula:

(369) ##STR00114##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(370) Compounds of Formula (VII) include R.sup.F1. In certain embodiments, R.sup.F1 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a. In certain embodiments, R.sup.F1 is hydrogen. In certain embodiments, R.sup.F1 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.F1 is optionally substituted C.sub.1-6 alkyl. In certain embodiments, R.sup.F1 is substituted methyl. In certain embodiments, R.sup.F1 is unsubstituted methyl. In certain embodiments, R.sup.F1 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.F1 is unsubstituted ethyl. In certain embodiments, R.sup.F1 is halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a. In certain embodiments, j is 1 and k is 1.

(371) In certain embodiments, j1 is 0 and k1 is 0.

(372) In one aspect of the present invention, provided are compounds of Formula (VIII′):

(373) ##STR00115##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(374) R.sup.A1z is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(375) each instance of R.sup.A3 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(376) R.sup.A6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(377) R.sup.B6a is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(378) R.sup.A8 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —OR.sup.a, —N(R.sup.b).sub.2, —SR.sup.a;

(379) or R.sup.B6a and R.sup.A8 are taken together with their intervening atoms to form an optionally substituted heterocyclic ring;

(380) each instance of R.sup.D6 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(381) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(382) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(383) c1 is 1, 2, 3, 4, 5, or 6;

(384) d1 is 1, 2, 3, or 4; and

(385) q1 is 1, 2, 3, or 4.

(386) In certain embodiments, a compound of Formula (VIII′) is of Formula (VIII).

(387) In one aspect of the resent invention, provided are compounds of Formula (VIII):

(388) ##STR00116##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(389) R.sup.A1 is hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(390) each instance of R.sup.A3 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(391) R.sup.A6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(392) R.sup.B6a is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(393) R.sup.A8 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —OR.sup.a, —N(R.sup.b).sub.2, —SR.sup.a;

(394) or R.sup.B6a and R.sup.A8 are taken together with their intervening atoms to form an optionally substituted heterocyclic ring;

(395) each instance of R.sup.D6 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2 or —SR.sup.a;

(396) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(397) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(398) c is 1, 2, 3, 4, 5, or 6;

(399) d is 1, 2, 3, or 4; and

(400) q is 1, 2, 3, or 4.

(401) In certain embodiments, the compound of Formulae (VIII′) or (VIII) is of the formula:

(402) ##STR00117##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(403) In certain embodiments, the compound of Formulae (VIII′) or (VIII) is of the formula:

(404) ##STR00118##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(405) Compounds of Formula (VIII′) include R.sup.A1z. In certain embodiments, R.sup.A1z is hydrogen. In certain embodiments, R.sup.A1z is halogen (e.g., F, Cl, Br, or I). In certain embodiments, R.sup.A1z is —Br. In certain embodiments, R.sup.A1z is —CN. In certain embodiments, R.sup.A1z is —SCN. In certain embodiments, R.sup.A1z is —NO.sub.2. In certain embodiments, R.sup.A1z is −N.sub.3. In certain embodiments, R.sup.A1z is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.A1z is substituted methyl. In certain embodiments, R.sup.A1z is unsubstituted methyl. In certain embodiments, R.sup.A1z is substituted or unsubstituted ethyl. In certain embodiments, R.sup.A1z is unsubstituted ethyl. In certain embodiments, R.sup.A1z is optionally substituted acyl (e.g., —C(═O)Me). In certain embodiments, R.sup.A1z is optionally substituted alkenyl (e.g., substituted or unsubstituted C.sub.2-6 alkenyl). In certain embodiments, R.sup.A1z is optionally substituted alkynyl (e.g., substituted or unsubstituted C.sub.2-6 alkynyl). In certain embodiments, R.sup.A1z is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.A1z is optionally substituted heterocyclyl (e.g., substituted or unsubstituted, 5- to 10-membered monocyclic or bicyclic heterocyclic ring, wherein one or two atoms in the heterocyclic ring are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A1z is optionally substituted aryl (e.g., substituted or unsubstituted, 6- to 10-membered aryl). In certain embodiments, R.sup.A1z is optionally substituted benzyl. In certain embodiments, R.sup.A1z is optionally substituted phenyl. In certain embodiments, R.sup.A1z is optionally substituted heteroaryl (e.g., substituted or unsubstituted, 5- to 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur; or substituted or unsubstituted, 9- to 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur). In certain embodiments, R.sup.A1z is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, R.sup.A1z is —OH. In certain embodiments, R.sup.A1 is —OMe. In certain embodiments, R.sup.A1z is —N(R.sup.b).sub.2 (e.g., —NMe.sub.2). In certain embodiments, R.sup.A1z is —NH.sub.2. In certain embodiments, R.sup.A1z is —NHC(═O)(optionally substituted C.sub.1-6 alkyl). In certain embodiments, R.sup.A1z is —NHC(═O)Me. In certain embodiments, R.sup.A1z is —NMe.sub.2. In certain embodiments, R.sup.A1z is —SR.sup.a (e.g., —SMe). In certain embodiments, R.sup.A1z is optionally substituted sulfonyl.

(406) Compounds of Formulae (VIII′) and (VIII) include R.sup.B6a. In certain embodiments, R.sup.B6a is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group. In certain embodiments, R.sup.B6a is hydrogen.

(407) Compounds of Formulae (VIII′) and (VIII) include R.sup.A8. In certain embodiments, R.sup.A8 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —OR.sup.a, —N(R.sup.b).sub.2, —SR.sup.a. In certain embodiments, R.sup.A8 is hydrogen. In certain embodiments, R.sup.A8 is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.A8 is optionally substituted C.sub.1-8 alkyl. In certain embodiments, R.sup.A8 is substituted methyl. In certain embodiments, R.sup.A8 is unsubstituted methyl. In certain embodiments, R.sup.A8 is substituted or unsubstituted ethyl. In certain embodiments, R.sup.A8 is unsubstituted ethyl. In certain embodiments, R.sup.A8 is —(CH.sub.2)COO(optionally substituted C.sub.1-6 alkyl). In certain embodiments, R.sup.A8 is —(CH.sub.2)COOMe. In certain embodiments, R.sup.B6a and R.sup.A8 are taken together with their intervening atoms to form an optionally substituted heterocyclic ring. In certain embodiments, R.sup.A8 is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —OR.sup.a, —N(R.sup.b).sub.2, —SR.sup.a.

(408) In one aspect of the present invention, provided are compounds of Formula (IX′):

(409) ##STR00119##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(410) each instance of R.sup.A3 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(411) R.sup.A6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(412) R.sup.B6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(413) each instance of R.sup.D7 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(414) R.sup.D6a is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —OR.sup.a, —N(R.sup.b).sub.2, —SR.sup.a, or optionally R.sup.D7 and R.sup.D6a are joined together with the intervening atoms to form optionally substituted heterocyclyl;

(415) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(416) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(417) c is 1, 2, 3, 4, 5, or 6;

(418) d is 1, 2, 3, or 4.

(419) In certain embodiments, the compound of Formula (IX′) is of Formula (IX).

(420) In certain embodiments, a compound described herein is of Formula (IX):

(421) ##STR00120##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(422) each instance of R.sup.A3 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(423) R.sup.A6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(424) R.sup.B6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(425) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(426) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(427) c is 1, 2, 3, 4, 5, or 6;

(428) d is 1, 2, 3, or 4; and

(429) q is 1, 2, 3, or 4.

(430) In certain embodiments, the compound of Formula (IX′) or (IX) is of the formula:

(431) ##STR00121##
or a pharmaceutically acceptable solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(432) In certain embodiments, the compound of Formula (IX′) or (IX) is of the formula:

(433) ##STR00122##
or a pharmaceutically acceptable solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(434) Compounds of Formula (IX′) include R.sup.D7. In certain embodiments, R.sup.D7 is hydrogen. In certain embodiments, R.sup.D7 is halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a. In certain embodiments, R.sup.D7 is —CN.

(435) Compounds of Formula (IX′) include R.sup.Da. In certain embodiments, R.sup.D6a is hydrogen. In certain embodiments, R.sup.D6a is optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —OR.sup.a, —N(R.sup.b).sub.2, —SR.sup.a, or R.sup.D7 and R.sup.D6a are joined together with the intervening atoms to form optionally substituted heterocyclyl. In certain embodiments, R.sup.D7 and R.sup.D6a are joined together with the intervening atoms to form optionally substituted heterocyclyl. In certain embodiments, R.sup.D6a is optionally substituted alkyl (e.g., substituted or unsubstituted C.sub.1-6 alkyl). In certain embodiments, R.sup.D6a is optionally substituted C.sub.1-6 alkyl. In certain embodiments, R.sup.D6a is of the formula: —(CH.sub.2).sub.xR.sup.D6b, wherein: x is 1, 2, 3, or 4; and R.sup.D6b is halogen, optionally substituted carbocyclyl, —OR.sup.a, or —N.sub.3. In certain embodiments, x is 1. In certain embodiments, x is 2. In certain embodiments, x is 3. In certain embodiments, x is 4. In certain embodiments, R.sup.D6b is halogen (e.g., F, Cl, Br, or I). In certain embodiments, RD is optionally substituted carbocyclyl (e.g., substituted or unsubstituted, 3- to 7-membered, monocyclic carbocyclyl comprising zero, one, or two double bonds in the carbocyclic ring system). In certain embodiments, R.sup.D6b is —OR.sup.a (e.g., —OH or —OMe). In certain embodiments, R.sup.D6b is —OR.sup.a, wherein R.sup.a is optionally substituted C.sub.1-6 alkyl. In certain embodiments, R.sup.D6 is —N.sub.3. In certain embodiments, R.sup.6a is of the formula: —(CH.sub.2).sub.2Br or —(CH.sub.2).sub.2N.sub.3. In certain embodiments, R.sup.D6a is substituted methyl. In certain embodiments, R.sup.D6a is unsubstituted methyl. In certain embodiments, R.sup.6a is substituted or unsubstituted ethyl. In certain embodiments, R.sup.D6a is unsubstituted ethyl. In certain embodiments, c is 1, d is 1, and q is 1. In certain embodiments, c is 1 and d is 1. In certain embodiments, R.sup.A3 is hydrogen, R.sup.A6 is hydrogen, and R.sup.D6 is hydrogen. In certain embodiments, R.sup.A3 is hydrogen and R.sup.A6 is hydrogen.

(436) In certain embodiments, c1 is 0, 1, d1 is 0, and q1 is 0. In certain embodiments, c1 is 0 and d1 is 0.

(437) In one aspect of the present invention, provided are compounds of Formula (X):

(438) ##STR00123##
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein:

(439) R.sup.A2 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group;

(440) each instance of R.sup.A3 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(441) R.sup.A4 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;

(442) R.sup.A5 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;

(443) R.sup.A6 is hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;

(444) each instance of R.sup.E2 is independently hydrogen, halogen, —CN, —SCN, —NO.sub.2, —N.sub.3, optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted sulfonyl, —OR.sup.a, —N(R.sup.b).sub.2, or —SR.sup.a;

(445) each instance of R.sup.a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;

(446) each instance of R.sup.b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two R.sup.b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;

(447) c is 1, 2, 3, 4, 5, or 6;

(448) d is 1, 2, 3, or 4; and

(449) p is 1, 2, 3, or 4.

(450) In certain embodiments, the compound of Formula (X) is of the formula:

(451) ##STR00124##
wherein R.sup.B8 is optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted aryl, or optionally substituted heteroaryl,
or a pharmaceutically acceptable solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.
Pharmaceutical Compositions, Kits, and Administration

(452) The present disclosure also provides pharmaceutical compositions comprising a compound described herein and optionally a pharmaceutically acceptable excipient. In certain embodiments, a compound described herein is a compound of Formulae (I′), (I), (IA), (II′), (II), (IIA), (III″), (III′), (IIIA), (III), (IV), (V′), (V), (VI), (VII), (VIII′), (VIII), (IX′), (IX), or (X), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. In certain embodiments, a compound described herein is a compound of Formulae (I′), (I), (IA), (II′), (II), (IIA), (III″), (III′), (IIIA), (III), (IV), (V′), (V), (VI), (VII), (VIII′), (VIII), (IX′), (IX), or (X), or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound described herein is provided in an effective amount in the pharmaceutical composition. In certain embodiments, the effective amount is a therapeutically effective amount. In certain embodiments, the effective amount is a prophylactically effective amount. In certain embodiments, a therapeutically effective amount is an amount effective for treating a disease (e.g., a proliferative disease (e.g., cancers (e.g., non-small cell lung cancer, or glioma), inflammatory diseases, autoimmune diseases), CNS disorder (e.g., drug addiction), metabolic disorder (e.g., diabetes), or infectious disease (e.g., bacterial infection or parasitic infection (e.g., malaria)). The pharmaceutical compositions described herein may be useful in treating parasitic infections. The pharmaceutical compositions described herein may be pharmaceutical compositions with anti-parasitic compounds, particularly pharmaceutical compositions with anti-plasmodial pharmaceutical compounds. The pharmaceutical compositions described herein may be useful in treating and/or preventing protozoan infections. The pharmaceutical compositions described herein may be useful in treating plasmodial infections in a subject in need thereof and/or preventing plasmodial infections in a subject at risk of developing a plasmodial infection. The compounds described herein may be anti-plasmodial compounds. The pharmaceutical compositions may be useful in treating protozoan infections in a subject in need thereof and/or preventing protozoan infections (e.g., plasmodial infections) in a subject at risk of developing a protozoan infection, treating plasmodial infections in a subject at risk of developing a plasmodial infection, treating infectious disease in a subject in need thereof and/or preventing an infectious disease in a subject at risk of developing an infectious disease (e.g., malaria), particularly treating parasitic diseases in a subject in need thereof, and as research tools (e.g., for studying plasmodial infections in a subject, biological sample, tissue, or cell). The pharmaceutical compositions may be useful as pharmaceutical compositions with anti-plasmodial compounds.

(453) In certain embodiments, the effective amount is an amount effective for inhibiting bacterial growth. In certain embodiments, the effective amount is an amount effective for killing microorganisms. In certain embodiments, the effective amount is an amount effective for killing bacteria. In certain embodiments, the effective amount is an amount effective for killing parasites.

(454) In certain embodiments, the bacterium which is the causative agent of the infection is a Gram-negative bacterium. In certain embodiments, the Gram-negative bacterium is selected from the group consisting of Escherichia, Citrobacter, Enterobacter, Klebsiella, Proteus, Serratia, Shigella, Salmonella, Morganella, Providencia, Edwardsiella, Erwinia, Hafnia, Yersinia, Acinetobacter, Vibrio, Aeromonas, Pseudomonas, Haemophilus, Pasteurella, Campylobacter, Helicobacter, Branhamella, Moraxella, Neisseria, Veillonella, Fusobacterium, Bacteroides, Actinobacillus, Aggregatibacter, Agrobacterium, Porphyromonas, Prevotella, Ruminobacter, Roseburia, Caulobacter, Francisella, Borrelia, Treponema, Brucella, and Rickettsia. In certain embodiments, the Gram-negative bacterium is selected from the group consisting of Escherichia coli, Morganella morganii, Branhamella catarrhalis, Veillonella parvula, Actinobacillus actinomycetemcomitans, Aggregatibacter actinomycetemcomitans, Caulobacter crescentus, and Treponema pallidum. In certain embodiments, the Gram-negative bacterium is selected from the group consisting of Escherichia coli, Citrobacter spp, Enterobacter spp, Klebsiella spp, Proteus spp, Serratia spp, Shigella spp, Salmonella spp, Morganella morganii, Providencia spp, Edwardsiella spp, Erwinia spp, Hafnia spp, Yersinia spp, Acinetobacter spp, Vibrio spp, Aeromonas spp, Pseudomonas spp, Haemophilus spp, Pasteurella spp, Campylobacter spp, Helicobacter spp, Branhamella catarrhalis, Moraxella spp, Neisseria spp, Veillonella parvula, Fusobacterium spp, Bacteroides spp, Actinobacillus actinomycetemcomitans, Aggregatibacter actinomycetemcomitans, Agrobacterium spp, Porphyromonas spp, Prevotella spp, Ruminobacter spp, Roseburia spp, Caulobacter crescentus, Francisella spp, Borrelia spp, Treponema pallidum, Brucella spp, and Rickettsia.

(455) In certain embodiments, the bacterium is a Gram-positive bacterium. In certain embodiments, the bacterium is at least one selected from the group consisting of Staphylococcus sp., Enterococcus sp., Escherichia coli, Bacillus sp., Salmonella sp., and Mycobacterium sp. In certain embodiments, the Gram-positive bacterium is selected from the group consisting of Staphylococcus, Streptococcus, Micrococcus, Peptococcus, Peptostreptococcus, Enterococcus, Bacillus, Clostridium, Lactobacillus, Listeria, Erysipelothrix, Propionibacterium, Eubacterium, Corynebacterium, Capnocytophaga, Bifidobacterium, and Gardnerella. In certain embodiments, the Gram-positive bacterium is selected from the group consisting of Staphylococcus spp, Streptococcus spp, Micrococcus spp, Peptococcus spp, Peptostreptococcus spp, Enterococcus spp, Bacillus spp, Clostridium spp, Lactobacillus spp, Listeria spp, Erysipelothrix spp, Propionibacterium spp, Eubacterium spp, Corynebacterium spp, Capnocytophaga spp, Bifidobacterium spp, and Gardnerella spp.

(456) In certain embodiments, the effective amount is an amount effective for treating a disease described herein. In certain embodiments, the effective amount is an amount effective for preventing a disease described herein. In certain embodiments, the effective amount is a therapeutically effective amount. In certain embodiments, the effective amount is an amount effective for inhibiting bacterial growth. In certain embodiments, the effective amount is an amount effective for killing microorganisms. In certain embodiments, the effective amount is an amount effective for killing protozoa. In certain embodiments, the effective amount is an amount effective for killing parasites. In certain embodiments, the effective amount is an amount effective for killing bacteria.

(457) In certain embodiments, the subject is an animal. The animal may be of either sex and may be at any stage of development. In certain embodiments, the subject described herein is a human. In certain embodiments, the subject is a non-human animal. In certain embodiments, the subject is a mammal. In certain embodiments, the subject is a non-human mammal. In certain embodiments, the subject is a domesticated animal, such as a dog, cat, cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a companion animal, such as a dog or cat. In certain embodiments, the subject is a livestock animal, such as a cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a zoo animal. In another embodiment, the subject is a research animal, such as a rodent (e.g., mouse, rat), dog, pig, or non-human primate. In certain embodiments, the animal is a genetically engineered animal. In certain embodiments, the animal is a transgenic animal (e.g., transgenic mice and transgenic pigs). In certain embodiments, the subject is a fish or reptile.

(458) In certain embodiments, the cell being contacted with a compound or composition described herein is in vitro. In certain embodiments, the cell being contacted with a compound or composition described herein is in vivo.

(459) Pharmaceutical compositions described herein can be prepared by any method known in the art of pharmacology. In general, such preparatory methods include bringing the compound described herein (i.e., the “active ingredient”) into association with a carrier or excipient, and/or one or more other accessory ingredients, and then, if necessary and/or desirable, shaping, and/or packaging the product into a desired single- or multi-dose unit.

(460) Pharmaceutical compositions can be prepared, packaged, and/or sold in bulk, as a single unit dose, and/or as a plurality of single unit doses. A “unit dose” is a discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient which would be administered to a subject and/or a convenient fraction of such a dosage, such as one-half or one-third of such a dosage.

(461) Relative amounts of the active ingredient, the pharmaceutically acceptable excipient, and/or any additional ingredients in a pharmaceutical composition described herein will vary, depending upon the identity, size, and/or condition of the subject treated and further depending upon the route by which the composition is to be administered. The composition may comprise between 0.1% and 100% (w/w) active ingredient.

(462) Pharmaceutically acceptable excipients used in the manufacture of provided pharmaceutical compositions include inert diluents, dispersing and/or granulating agents, surface active agents and/or emulsifiers, disintegrating agents, binding agents, preservatives, buffering agents, lubricating agents, and/or oils. Excipients such as cocoa butter and suppository waxes, coloring agents, coating agents, sweetening, flavoring, and perfuming agents may also be present in the composition.

(463) Exemplary diluents include calcium carbonate, sodium carbonate, calcium phosphate, dicalcium phosphate, calcium sulfate, calcium hydrogen phosphate, sodium phosphate lactose, sucrose, cellulose, microcrystalline cellulose, kaolin, mannitol, sorbitol, inositol, sodium chloride, dry starch, cornstarch, powdered sugar, and mixtures thereof.

(464) Exemplary granulating and/or dispersing agents include potato starch, corn starch, tapioca starch, sodium starch glycolate, clays, alginic acid, guar gum, citrus pulp, agar, bentonite, cellulose, and wood products, natural sponge, cation-exchange resins, calcium carbonate, silicates, sodium carbonate, cross-linked poly(vinyl-pyrrolidone) (crospovidone), sodium carboxymethyl starch (sodium starch glycolate), carboxymethyl cellulose, cross-linked sodium carboxymethyl cellulose (croscarmellose), methylcellulose, pregelatinized starch (starch 1500), microcrystalline starch, water insoluble starch, calcium carboxymethyl cellulose, magnesium aluminum silicate (Veegum), sodium lauryl sulfate, quaternary ammonium compounds, and mixtures thereof.

(465) Exemplary surface active agents and/or emulsifiers include natural emulsifiers (e.g., acacia, agar, alginic acid, sodium alginate, tragacanth, chondrux, cholesterol, xanthan, pectin, gelatin, egg yolk, casein, wool fat, cholesterol, wax, and lecithin), colloidal clays (e.g., bentonite (aluminum silicate) and Veegum (magnesium aluminum silicate)), long chain amino acid derivatives, high molecular weight alcohols (e.g., stearyl alcohol, cetyl alcohol, oleyl alcohol, triacetin monostearate, ethylene glycol distearate, glyceryl monostearate, and propylene glycol monostearate, polyvinyl alcohol), carbomers (e.g., carboxy polymethylene, polyacrylic acid, acrylic acid polymer, and carboxyvinyl polymer), carrageenan, cellulosic derivatives (e.g., carboxymethylcellulose sodium, powdered cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose), sorbitan fatty acid esters (e.g., polyoxyethylene sorbitan monolaurate (Tween® 20), polyoxyethylene sorbitan (Tween® 60), polyoxyethylene sorbitan monooleate (Tween® 80), sorbitan monopalmitate (Span® 40), sorbitan monostearate (Span® 60), sorbitan tristearate (Span® 65), glyceryl monooleate, sorbitan monooleate (Span® 80), polyoxyethylene esters (e.g., polyoxyethylene monostearate (Myrj© 45), polyoxyethylene hydrogenated castor oil, polyethoxylated castor oil, polyoxymethylene stearate, and Solutol®), sucrose fatty acid esters, polyethylene glycol fatty acid esters (e.g., Cremophor®), polyoxyethylene ethers, (e.g., polyoxyethylene lauryl ether (Brij® 30)), poly(vinyl-pyrrolidone), diethylene glycol monolaurate, triethanolamine oleate, sodium oleate, potassium oleate, ethyl oleate, oleic acid, ethyl laurate, sodium lauryl sulfate, Pluronic® F-68, poloxamer P-188, cetrimonium bromide, cetylpyridinium chloride, benzalkonium chloride, docusate sodium, and/or mixtures thereof.

(466) Exemplary binding agents include starch (e.g., cornstarch and starch paste), gelatin, sugars (e.g., sucrose, glucose, dextrose, dextrin, molasses, lactose, lactitol, mannitol, etc.), natural and synthetic gums (e.g., acacia, sodium alginate, extract of Irish moss, panwar gum, ghatti gum, mucilage of isapol husks, carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, cellulose acetate, poly(vinyl-pyrrolidone), magnesium aluminum silicate (Veegum®), and larch arabogalactan), alginates, polyethylene oxide, polyethylene glycol, inorganic calcium salts, silicic acid, polymethacrylates, waxes, water, alcohol, and/or mixtures thereof.

(467) Exemplary preservatives include antioxidants, chelating agents, antimicrobial preservatives, antifungal preservatives, antiprotozoan preservatives, alcohol preservatives, acidic preservatives, and other preservatives. In certain embodiments, the preservative is an antioxidant. In other embodiments, the preservative is a chelating agent.

(468) Exemplary antioxidants include alpha tocopherol, ascorbic acid, acorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, sodium metabisulfite, and sodium sulfite.

(469) Exemplary chelating agents include ethylenediaminetetraacetic acid (EDTA) and salts and hydrates thereof (e.g., sodium edetate, disodium edetate, trisodium edetate, calcium disodium edetate, dipotassium edetate, and the like), citric acid and salts and hydrates thereof (e.g., citric acid monohydrate), fumaric acid and salts and hydrates thereof, malic acid and salts and hydrates thereof, phosphoric acid and salts and hydrates thereof, and tartaric acid and salts and hydrates thereof. Exemplary antimicrobial preservatives include benzalkonium chloride, benzethonium chloride, benzyl alcohol, bronopol, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, ethyl alcohol, glycerin, hexetidine, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric nitrate, propylene glycol, and thimerosal.

(470) Exemplary antifungal preservatives include butyl paraben, methyl paraben, ethyl paraben, propyl paraben, benzoic acid, hydroxybenzoic acid, potassium benzoate, potassium sorbate, sodium benzoate, sodium propionate, and sorbic acid.

(471) Exemplary alcohol preservatives include ethanol, polyethylene glycol, phenol, phenolic compounds, bisphenol, chlorobutanol, hydroxybenzoate, and phenylethyl alcohol.

(472) Exemplary acidic preservatives include vitamin A, vitamin C, vitamin E, beta-carotene, citric acid, acetic acid, dehydroacetic acid, ascorbic acid, sorbic acid, and phytic acid.

(473) Other preservatives include tocopherol, tocopherol acetate, deteroxime mesylate, cetrimide, butylated hydroxyanisol (BHA), butylated hydroxytoluened (BHT), ethylenediamine, sodium lauryl sulfate (SLS), sodium lauryl ether sulfate (SLES), sodium bisulfite, sodium metabisulfite, potassium sulfite, potassium metabisulfite, Glydant® Plus, Phenonip®, methylparaben, Germall® 115, Germaben® II, Neolone®, Kathon®, and Euxyl®.

(474) Exemplary buffering agents include citrate buffer solutions, acetate buffer solutions, phosphate buffer solutions, ammonium chloride, calcium carbonate, calcium chloride, calcium citrate, calcium glubionate, calcium gluceptate, calcium gluconate, D-gluconic acid, calcium glycerophosphate, calcium lactate, propanoic acid, calcium levulinate, pentanoic acid, dibasic calcium phosphate, phosphoric acid, tribasic calcium phosphate, calcium hydroxide phosphate, potassium acetate, potassium chloride, potassium gluconate, potassium mixtures, dibasic potassium phosphate, monobasic potassium phosphate, potassium phosphate mixtures, sodium acetate, sodium bicarbonate, sodium chloride, sodium citrate, sodium lactate, dibasic sodium phosphate, monobasic sodium phosphate, sodium phosphate mixtures, tromethamine, magnesium hydroxide, aluminum hydroxide, alginic acid, pyrogen-free water, isotonic saline, Ringer's solution, ethyl alcohol, and mixtures thereof.

(475) Exemplary lubricating agents include magnesium stearate, calcium stearate, stearic acid, silica, talc, malt, glyceryl behanate, hydrogenated vegetable oils, polyethylene glycol, sodium benzoate, sodium acetate, sodium chloride, leucine, magnesium lauryl sulfate, sodium lauryl sulfate, and mixtures thereof.

(476) Exemplary natural oils include almond, apricot kernel, avocado, babassu, bergamot, black current seed, borage, cade, camomile, canola, caraway, carnauba, castor, cinnamon, cocoa butter, coconut, cod liver, coffee, corn, cotton seed, emu, eucalyptus, evening primrose, fish, flaxseed, geraniol, gourd, grape seed, hazel nut, hyssop, isopropyl myristate, jojoba, kukui nut, lavandin, lavender, lemon, litsea cubeba, macademia nut, mallow, mango seed, meadowfoam seed, mink, nutmeg, olive, orange, orange roughy, palm, palm kernel, peach kernel, peanut, poppy seed, pumpkin seed, rapeseed, rice bran, rosemary, safflower, sandalwood, sasquana, savoury, sea buckthorn, sesame, shea butter, silicone, soybean, sunflower, tea tree, thistle, tsubaki, vetiver, walnut, and wheat germ oils. Exemplary synthetic oils include, but are not limited to, butyl stearate, caprylic triglyceride, capric triglyceride, cyclomethicone, diethyl sebacate, dimethicone 360, isopropyl myristate, mineral oil, octyldodecanol, oleyl alcohol, silicone oil, and mixtures thereof.

(477) Liquid dosage forms for oral and parenteral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredients, the liquid dosage forms may comprise inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (e.g., cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. In certain embodiments for parenteral administration, the conjugates described herein are mixed with solubilizing agents such as Cremophor®, alcohols, oils, modified oils, glycols, polysorbates, cyclodextrins, polymers, and mixtures thereof.

(478) Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions can be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation can be a sterile injectable solution, suspension, or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that can be employed are water, Ringer's solution, U.S.P., and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or di-glycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables.

(479) The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use.

(480) In order to prolong the effect of a drug, it is often desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This can be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution, which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form may be accomplished by dissolving or suspending the drug in an oil vehicle.

(481) Compositions for rectal or vaginal administration are typically suppositories which can be prepared by mixing the conjugates described herein with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol, or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active ingredient.

(482) Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active ingredient is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or (a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, (b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, (c) humectants such as glycerol, (d) disintegrating agents such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, (e) solution retarding agents such as paraffin, (f) absorption accelerators such as quaternary ammonium compounds, (g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, (h) absorbents such as kaolin and bentonite clay, and (i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets, and pills, the dosage form may include a buffering agent.

(483) Solid compositions of a similar type can be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the art of pharmacology. They may optionally comprise opacifying agents and can be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of encapsulating compositions which can be used include polymeric substances and waxes. Solid compositions of a similar type can be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polethylene glycols and the like.

(484) The active ingredient can be in a micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings, and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active ingredient can be admixed with at least one inert diluent such as sucrose, lactose, or starch. Such dosage forms may comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may comprise buffering agents. They may optionally comprise opacifying agents and can be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of encapsulating agents which can be used include polymeric substances and waxes.

(485) Dosage forms for topical and/or transdermal administration of a compound described herein may include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants, and/or patches. Generally, the active ingredient is admixed under sterile conditions with a pharmaceutically acceptable carrier or excipient and/or any needed preservatives and/or buffers as can be required. Additionally, the present disclosure contemplates the use of transdermal patches, which often have the added advantage of providing controlled delivery of an active ingredient to the body. Such dosage forms can be prepared, for example, by dissolving and/or dispensing the active ingredient in the proper medium. Alternatively or additionally, the rate can be controlled by either providing a rate controlling membrane and/or by dispersing the active ingredient in a polymer matrix and/or gel.

(486) Suitable devices for use in delivering intradermal pharmaceutical compositions described herein include short needle devices. Intradermal compositions can be administered by devices which limit the effective penetration length of a needle into the skin. Alternatively or additionally, conventional syringes can be used in the classical mantoux method of intradermal administration. Jet injection devices which deliver liquid formulations to the dermis via a liquid jet injector and/or via a needle which pierces the stratum corneum and produces a jet which reaches the dermis are suitable. Ballistic powder/particle delivery devices which use compressed gas to accelerate the compound in powder form through the outer layers of the skin to the dermis are suitable.

(487) Formulations suitable for topical administration include, but are not limited to, liquid and/or semi-liquid preparations such as liniments, lotions, oil-in-water and/or water-in-oil emulsions such as creams, ointments, and/or pastes, and/or solutions and/or suspensions. Topically administrable formulations may, for example, comprise from about 1% to about 10% (w/w) active ingredient, although the concentration of the active ingredient can be as high as the solubility limit of the active ingredient in the solvent. Formulations for topical administration may further comprise one or more of the additional ingredients described herein.

(488) A pharmaceutical composition described herein can be prepared, packaged, and/or sold in a formulation suitable for pulmonary administration via the buccal cavity. Such a formulation may comprise dry particles which comprise the active ingredient and which have a diameter in the range from about 0.5 to about 7 nanometers, or from about 1 to about 6 nanometers. Such compositions are conveniently in the form of dry powders for administration using a device comprising a dry powder reservoir to which a stream of propellant can be directed to disperse the powder and/or using a self-propelling solvent/powder dispensing container such as a device comprising the active ingredient dissolved and/or suspended in a low-boiling propellant in a sealed container. Such powders comprise particles wherein at least 98% of the particles by weight have a diameter greater than 0.5 nanometers and at least 95% of the particles by number have a diameter less than 7 nanometers. Alternatively, at least 95% of the particles by weight have a diameter greater than 1 nanometer and at least 90% of the particles by number have a diameter less than 6 nanometers. Dry powder compositions may include a solid fine powder diluent such as sugar and are conveniently provided in a unit dose form.

(489) Low boiling propellants generally include liquid propellants having a boiling point of below 65° F. at atmospheric pressure. Generally the propellant may constitute 50 to 99.9% (w/w) of the composition, and the active ingredient may constitute 0.1 to 20% (w/w) of the composition. The propellant may further comprise additional ingredients such as a liquid non-ionic and/or solid anionic surfactant and/or a solid diluent (which may have a particle size of the same order as particles comprising the active ingredient).

(490) Pharmaceutical compositions described herein formulated for pulmonary delivery may provide the active ingredient in the form of droplets of a solution and/or suspension. Such formulations can be prepared, packaged, and/or sold as aqueous and/or dilute alcoholic solutions and/or suspensions, optionally sterile, comprising the active ingredient, and may conveniently be administered using any nebulization and/or atomization device. Such formulations may further comprise one or more additional ingredients including, but not limited to, a flavoring agent such as saccharin sodium, a volatile oil, a buffering agent, a surface active agent, and/or a preservative such as methylhydroxybenzoate. The droplets provided by this route of administration may have an average diameter in the range from about 0.1 to about 200 nanometers.

(491) Formulations described herein as being useful for pulmonary delivery are useful for intranasal delivery of a pharmaceutical composition described herein. Another formulation suitable for intranasal administration is a coarse powder comprising the active ingredient and having an average particle from about 0.2 to 500 micrometers. Such a formulation is administered by rapid inhalation through the nasal passage from a container of the powder held close to the nares.

(492) Formulations for nasal administration may, for example, comprise from about as little as 0.1% (w/w) to as much as 100% (w/w) of the active ingredient, and may comprise one or more of the additional ingredients described herein. A pharmaceutical composition described herein can be prepared, packaged, and/or sold in a formulation for buccal administration. Such formulations may, for example, be in the form of tablets and/or lozenges made using conventional methods, and may contain, for example, 0.1 to 20% (w/w) active ingredient, the balance comprising an orally dissolvable and/or degradable composition and, optionally, one or more of the additional ingredients described herein. Alternately, formulations for buccal administration may comprise a powder and/or an aerosolized and/or atomized solution and/or suspension comprising the active ingredient. Such powdered, aerosolized, and/or aerosolized formulations, when dispersed, may have an average particle and/or droplet size in the range from about 0.1 to about 200 nanometers, and may further comprise one or more of the additional ingredients described herein.

(493) A pharmaceutical composition described herein can be prepared, packaged, and/or sold in a formulation for ophthalmic administration. Such formulations may, for example, be in the form of eye drops including, for example, a 0.1-1.0% (w/w) solution and/or suspension of the active ingredient in an aqueous or oily liquid carrier or excipient. Such drops may further comprise buffering agents, salts, and/or one or more other of the additional ingredients described herein. Other ophthalmically-administrable formulations which are useful include those which comprise the active ingredient in microcrystalline form and/or in a liposomal preparation. Ear drops and/or eye drops are also contemplated as being within the scope of this disclosure.

(494) Although the descriptions of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions which are suitable for administration to humans, it will be understood by the skilled artisan that such compositions are generally suitable for administration to animals of all sorts. Modification of pharmaceutical compositions suitable for administration to humans in order to render the compositions suitable for administration to various animals is well understood, and the ordinarily skilled veterinary pharmacologist can design and/or perform such modification with ordinary experimentation.

(495) Compounds provided herein are typically formulated in dosage unit form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily usage of the compositions described herein will be decided by a physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular subject or organism will depend upon a variety of factors including the disease being treated and the severity of the disorder; the activity of the specific active ingredient employed; the specific composition employed; the age, body weight, general health, sex, and diet of the subject; the time of administration, route of administration, and rate of excretion of the specific active ingredient employed; the duration of the treatment; drugs used in combination or coincidental with the specific active ingredient employed; and like factors well known in the medical arts.

(496) The compounds and compositions provided herein can be administered by any route, including enteral (e.g., oral), parenteral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal, interdermal, rectal, intravaginal, intraperitoneal, topical (as by powders, ointments, creams, and/or drops), mucosal, nasal, bucal, sublingual; by intratracheal instillation, bronchial instillation, and/or inhalation; and/or as an oral spray, nasal spray, and/or aerosol. Specifically contemplated routes are oral administration, intravenous administration (e.g., systemic intravenous injection), regional administration via blood and/or lymph supply, and/or direct administration to an affected site. In general, the most appropriate route of administration will depend upon a variety of factors including the nature of the agent (e.g., its stability in the environment of the gastrointestinal tract), and/or the condition of the subject (e.g., whether the subject is able to tolerate oral administration). In certain embodiments, the compound or pharmaceutical composition described herein is suitable for topical administration to the eye of a subject.

(497) The exact amount of a compound required to achieve an effective amount will vary from subject to subject, depending, for example, on species, age, and general condition of a subject, severity of the side effects or disorder, identity of the particular compound, mode of administration, and the like. An effective amount may be included in a single dose (e.g., single oral dose) or multiple doses (e.g., multiple oral doses). In certain embodiments, when multiple doses are administered to a subject or applied to a biological sample, tissue, or cell, any two doses of the multiple doses include different or substantially the same amounts of a compound described herein. In certain embodiments, when multiple doses are administered to a subject or applied to a biological sample, tissue, or cell, the frequency of administering the multiple doses to the subject or applying the multiple doses to the biological sample, tissue, or cell is three doses a day, two doses a day, one dose a day, one dose every other day, one dose every third day, one dose every week, one dose every two weeks, one dose every three weeks, or one dose every four weeks. In certain embodiments, the frequency of administering the multiple doses to the subject or applying the multiple doses to the biological sample, tissue, or cell is one dose per day. In certain embodiments, the frequency of administering the multiple doses to the subject or applying the multiple doses to the biological sample, tissue, or cell is two doses per day. In certain embodiments, the frequency of administering the multiple doses to the subject or applying the multiple doses to the biological sample, tissue, or cell is three doses per day. In certain embodiments, when multiple doses are administered to a subject or applied to a biological sample, tissue, or cell, the duration between the first dose and last dose of the multiple doses is one day, two days, four days, one week, two weeks, three weeks, one month, two months, three months, four months, six months, nine months, one year, two years, three years, four years, five years, seven years, ten years, fifteen years, twenty years, or the lifetime of the subject, tissue, or cell. In certain embodiments, the duration between the first dose and last dose of the multiple doses is three months, six months, or one year. In certain embodiments, the duration between the first dose and last dose of the multiple doses is the lifetime of the subject, tissue, or cell. In certain embodiments, a dose (e.g., a single dose, or any dose of multiple doses) described herein includes independently between 0.1 μg and 1 μg, between 0.001 mg and 0.01 mg, between 0.01 mg and 0.1 mg, between 0.1 mg and 1 mg, between 1 mg and 3 mg, between 3 mg and 10 mg, between 10 mg and 30 mg, between 30 mg and 100 mg, between 100 mg and 300 mg, between 300 mg and 1,000 mg, or between 1 g and 10 g, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 1 mg and 3 mg, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 3 mg and 10 mg, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 10 mg and 30 mg, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 30 mg and 100 mg, inclusive, of a compound described herein.

(498) Dose ranges as described herein provide guidance for the administration of provided pharmaceutical compositions to an adult. The amount to be administered to, for example, a child or an adolescent can be determined by a medical practitioner or person skilled in the art and can be lower or the same as that administered to an adult.

(499) A compound or composition, as described herein, can be administered in combination with one or more additional pharmaceutical agents (e.g., therapeutically and/or prophylactically active agents). The compounds or compositions can be administered in combination with additional pharmaceutical agents that improve their activity (e.g., activity (e.g., potency and/or efficacy) in treating a disease in a subject in need thereof, in preventing a disease in a subject in need thereof, to improve bioavailability, improve safety, reduce drug resistance, reduce and/or modify metabolism, inhibit excretion, and/or modify distribution in a subject, biological sample, tissue, or cell. It will also be appreciated that the therapy employed may achieve a desired effect for the same disorder, and/or it may achieve different effects. In certain embodiments, a pharmaceutical composition described herein including a compound described herein and an additional pharmaceutical agent shows a synergistic effect that is absent in a pharmaceutical composition including one of the compound and the additional pharmaceutical agent, but not both.

(500) The compound or composition can be administered concurrently with, prior to, or subsequent to one or more additional pharmaceutical agents, which may be useful as, e.g., combination therapies. Pharmaceutical agents include therapeutically active agents. Pharmaceutical agents also include prophylactically active agents. Pharmaceutical agents include small organic molecules such as drug compounds (e.g., compounds approved for human or veterinary use by the U.S. Food and Drug Administration as provided in the Code of Federal Regulations (CFR)), peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNAs, RNAs, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, lipids, hormones, vitamins, and cells. In certain embodiments, the additional pharmaceutical agent is a pharmaceutical agent useful for treating and/or preventing a disease (e.g., proliferative disease, inflammatory disease, autoimmune disease, genetic disease, hematological disease, CNS disorder, neurological disease, painful condition, psychiatric disorder, metabolic disorder, or infectious disease). Each additional pharmaceutical agent may be administered at a dose and/or on a time schedule determined for that pharmaceutical agent. The additional pharmaceutical agents may also be administered together with each other and/or with the compound or composition described herein in a single dose or administered separately in different doses. The particular combination to employ in a regimen will take into account compatibility of the compound described herein with the additional pharmaceutical agent(s) and/or the desired therapeutic and/or prophylactic effect to be achieved. In general, it is expected that the additional pharmaceutical agent(s) in combination be utilized at levels that do not exceed the levels at which they are utilized individually. In some embodiments, the levels utilized in combination will be lower than those utilized individually.

(501) The additional pharmaceutical agents include, but are not limited to, anti-proliferative agents, anti-cancer agents, anti-angiogenesis agents, anti-inflammatory agents, immunosuppressants, anti-bacterial agents, anti-viral agents, cardiovascular agents, cholesterol-lowering agents, anti-diabetic agents, anti-allergic agents, contraceptive agents, pain-relieving agents, and a combination thereof. In certain embodiments, the additional pharmaceutical agent is an anti-proliferative agent (e.g., anti-cancer agent). In certain embodiments, the additional pharmaceutical agent is an anti-leukemia agent. In certain embodiments, the additional pharmaceutical agent is ABITREXATE (methotrexate), ADE, Adriamycin RDF (doxorubicin hydrochloride), Ambochlorin (chlorambucil), ARRANON (nelarabine), ARZERRA (ofatumumab), BOSULIF (bosutinib), BUSULFEX (busulfan), CAMPATH (alemtuzumab), CERUBIDINE (daunorubicin hydrochloride), CLAFEN (cyclophosphamide), CLOFAREX (clofarabine), CLOLAR (clofarabine), CVP, CYTOSAR-U (cytarabine), CYTOXAN (cyclophosphamide), ERWINAZE (Asparaginase Erwinia Chrysanthemi), FLUDARA (fludarabine phosphate), FOLEX (methotrexate), FOLEX PFS (methotrexate), GAZYVA (obinutuzumab), GLEEVEC (imatinib mesylate), Hyper-CVAD, ICLUSIG (ponatinib hydrochloride), IMBRUVICA (ibrutinib), LEUKERAN (chlorambucil), LINFOLIZIN (chlorambucil), MARQIBO (vincristine sulfate liposome), METHOTREXATE LPF (methorexate), MEXATE (methotrexate), MEXATE-AQ (methotrexate), mitoxantrone hydrochloride, MUSTARGEN (mechlorethamine hydrochloride), MYLERAN (busulfan), NEOSAR (cyclophosphamide), ONCASPAR (Pegaspargase), PURINETHOL (mercaptopurine), PURIXAN (mercaptopurine), Rubidomycin (daunorubicin hydrochloride), SPRYCEL (dasatinib), SYNRIBO (omacetaxine mepesuccinate), TARABINE PFS (cytarabine), TASIGNA (nilotinib), TREANDA (bendamustine hydrochloride), TRISENOX (arsenic trioxide), VINCASAR PFS (vincristine sulfate), ZYDELIG (idelalisib), or a combination thereof. In certain embodiments, the additional pharmaceutical agent is an anti-lymphoma agent. In certain embodiments, the additional pharmaceutical agent is ABITREXATE (methotrexate), ABVD, ABVE, ABVE-PC, ADCETRIS (brentuximab vedotin), ADRIAMYCIN PFS (doxorubicin hydrochloride), ADRIAMYCIN RDF (doxorubicin hydrochloride), AMBOCHLORIN (chlorambucil), AMBOCLORIN (chlorambucil), ARRANON (nelarabine), BEACOPP, BECENUM (carmustine), BELEODAQ (belinostat), BEXXAR (tositumomab and iodine I 131 tositumomab), BICNU (carmustine), BLENOXANE (bleomycin), CARMUBRIS (carmustine), CHOP, CLAFEN (cyclophosphamide), COPP, COPP-ABV, CVP, CYTOXAN (cyclophosphamide), DEPOCYT (liposomal cytarabine), DTIC-DOME (dacarbazine), EPOCH, FOLEX (methotrexate), FOLEX PFS (methotrexate), FOLOTYN (pralatrexate), HYPER-CVAD, ICE, IMBRUVICA (ibrutinib), INTRON A (recombinant interferon alfa-2b), ISTODAX (romidepsin), LEUKERAN (chlorambucil), LINFOLIZIN (chlorambucil), Lomustine, MATULANE (procarbazine hydrochloride), METHOTREXATE LPF (methotrexate), MEXATE (methotrexate), MEXATE-AQ (methotrexate), MOPP, MOZOBIL (plerixafor), MUSTARGEN (mechlorethamine hydrochloride), NEOSAR (cyclophosphamide), OEPA, ONTAK (denileukin diftitox), OPPA, R-CHOP, REVLIMID (lenalidomide), RITUXAN (rituximab), STANFORD V, TREANDA (bendamustine hydrochloride), VAMP, VELBAN (vinblastine sulfate), VELCADE (bortezomib), VELSAR (vinblastine sulfate), VINCASAR PFS (vincristine sulfate), ZEVALIN (ibritumomab tiuxetan), ZOLINZA (vorinostat), ZYDELIG (idelalisib), or a combination thereof. In certain embodiments, the additional pharmaceutical agent is REVLIMID (lenalidomide), DACOGEN (decitabine), VIDAZA (azacitidine), CYTOSAR-U (cytarabine), IDAMYCIN (idarubicin), CERUBIDINE (daunorubicin), LEUKERAN (chlorambucil), NEOSAR (cyclophosphamide), FLUDARA (fludarabine), LEUSTATIN (cladribine), or a combination thereof. In certain embodiments, the additional pharmaceutical agent is ABITREXATE (methotrexate), ABRAXANE (paclitaxel albumin-stabilized nanoparticle formulation), AC, AC-T, ADE, ADRIAMYCIN PFS (doxorubicin hydrochloride), ADRUCIL (fluorouracil), AFINITOR (everolimus), AFINITOR DISPERZ (everolimus), ALDARA (imiquimod), ALIMTA (pemetrexed disodium), AREDIA (pamidronate disodium), ARIMIDEX (anastrozole), AROMASIN (exemestane), AVASTIN (bevacizumab), BECENUM (carmustine), BEP, BICNU (carmustine), BLENOXANE (bleomycin), CAF, CAMPTOSAR (irinotecan hydrochloride), CAPOX, CAPRELSA (vandetanib), CARBOPLATIN-TAXOL, CARMUBRIS (carmustine), CASODEX (bicalutamide), CEENU (lomustine), CERUBIDINE (daunorubicin hydrochloride), CERVARIX (recombinant HPV bivalent vaccine), CLAFEN (cyclophosphamide), CMF, COMETRIQ (cabozantinib-s-malate), COSMEGEN (dactinomycin), CYFOS (ifosfamide), CYRAMZA (ramucirumab), CYTOSAR-U (cytarabine), CYTOXAN (cyclophosphamide), DACOGEN (decitabine), DEGARELIX, DOXIL (doxorubicin hydrochloride liposome), DOXORUBICIN HYDROCHLORIDE, DOX-SL (doxorubicin hydrochloride liposome), DTIC-DOME (dacarbazine), EFUDEX (fluorouracil), ELLENCE (epirubicin hydrochloride), ELOXATIN (oxaliplatin), ERBITUX (cetuximab), ERIVEDGE (vismodegib), ETOPOPHOS (etoposide phosphate), EVACET (doxorubicin hydrochloride liposome), FARESTON (toremifene), FASLODEX (fulvestrant), FEC, FEMARA (letrozole), FLUOROPLEX (fluorouracil), FOLEX (methotrexate), FOLEX PFS (methotrexate), FOLFIRI, FOLFIRI-BEVACIZUMAB, FOLFIRI-CETUXIMAB, FOLFIRINOX, FOLFOX, FU-LV, GARDASIL (recombinant human papillomavirus (HPV) quadrivalent vaccine), GEMCITABINE-CISPLATIN, GEMCITABINE-OXALIPLATIN, GEMZAR (gemcitabine hydrochloride), GILOTRIF (afatinib dimaleate), GLEEVEC (imatinib mesylate), GLIADEL (carmustine implant), GLIADEL WAFER (carmustine implant), HERCEPTIN (trastuzumab), HYCAMTIN (topotecan hydrochloride), IFEX (ifosfamide), IFOSFAMIDUM (ifosfamide), INLYTA (axitinib), INTRON A (recombinant interferon alfa-2b), IRESSA (gefitinib), IXEMPRA (ixabepilone), JAKAFI (ruxolitinib phosphate), JEVTANA (cabazitaxel), KADCYLA (ado-trastuzumab emtansine), KEYTRUDA (pembrolizumab), KYPROLIS (carfilzomib), LIPODOX (doxorubicin hydrochloride liposome), LUPRON (leuprolide acetate), LUPRON DEPOT (leuprolide acetate), LUPRON DEPOT-3 MONTH (leuprolide acetate), LUPRON DEPOT-4 MONTH (leuprolide acetate), LUPRON DEPOT-PED (leuprolide acetate), MEGACE (megestrol acetate), MEKINIST (trametinib), METHAZOLASTONE (temozolomide), METHOTREXATE LPF (methotrexate), MEXATE (methotrexate), MEXATE-AQ (methotrexate), MITOXANTRONE HYDROCHLORIDE, MITOZYTREX (mitomycin c), MOZOBIL (plerixafor), MUSTARGEN (mechlorethamine hydrochloride), MUTAMYCIN (mitomycin c), MYLOSAR (azacitidine), NAVELBINE (vinorelbine tartrate), NEOSAR (cyclophosphamide), NEXAVAR (sorafenib tosylate), NOLVADEX (tamoxifen citrate), NOVALDEX (tamoxifen citrate), OFF, PAD, PARAPLAT (carboplatin), PARAPLATIN (carboplatin), PEG-INTRON (peginterferon alfa-2b), PEMETREXED DISODIUM, PERJETA (pertuzumab), PLATINOL (cisplatin), PLATINOL-AQ (cisplatin), POMALYST (pomalidomide), prednisone, PROLEUKIN (aldesleukin), PROLIA (denosumab), PROVENGE (sipuleucel-t), REVLIMID (lenalidomide), RUBIDOMYCIN (daunorubicin hydrochloride), SPRYCEL (dasatinib), STIVARGA (regorafenib), SUTENT (sunitinib malate), SYLATRON (peginterferon alfa-2b), SYLVANT (siltuximab), SYNOVIR (thalidomide), TAC, TAFINLAR (dabrafenib), TARABINE PFS (cytarabine), TARCEVA (erlotinib hydrochloride), TASIGNA (nilotinib), TAXOL (paclitaxel), TAXOTERE (docetaxel), TEMODAR (temozolomide), THALOMID (thalidomide), TOPOSAR (etoposide), TORISEL (temsirolimus), TPF, TRISENOX (arsenic trioxide), TYKERB (lapatinib ditosylate), VECTIBIX (panitumumab), VEIP, VELBAN (vinblastine sulfate), VELCADE (bortezomib), VELSAR (vinblastine sulfate), VEPESID (etoposide), VIADUR (leuprolide acetate), VIDAZA (azacitidine), VINCASAR PFS (vincristine sulfate), VOTRIENT (pazopanib hydrochloride), WELLCOVORIN (leucovorin calcium), XALKORI (crizotinib), XELODA (capecitabine), XELOX, XGEVA (denosumab), XOFIGO (radium 223 dichloride), XTANDI (enzalutamide), YERVOY (ipilimumab), ZALTRAP (ziv-aflibercept), ZELBORAF (vemurafenib), ZOLADEX (goserelin acetate), ZOMETA (zoledronic acid), ZYKADIA (ceritinib), ZYTIGA (abiraterone acetate), ENMD-2076, PCI-32765, AC220, dovitinib lactate (TKI258, CHIR-258), BIBW 2992 (TOVOK.sup.TM), SGX523, PF-04217903, PF-02341066, PF-299804, BMS-777607, ABT-869, MP470, BIBF 1120 (VARGATEF®), AP24534, JNJ-26483327, MGCD265, DCC-2036, BMS-690154, CEP-11981, tivozanib (AV-951), OSI-930, MM-121, XL-184, XL-647, and/or XL228), proteasome inhibitors (e.g., bortezomib (Velcade)), mTOR inhibitors (e.g., rapamycin, temsirolimus (CCI-779), everolimus (RAD-001), ridaforolimus, AP23573 (Ariad), AZD8055 (AstraZeneca), BEZ235 (Novartis), BGT226 (Norvartis), XL765 (Sanofi Aventis), PF-4691502 (Pfizer), GDC0980 (Genetech), SF1126 (Semafoe) and OSI-027 (OSI)), oblimersen, gemcitabine, carminomycin, leucovorin, pemetrexed, cyclophosphamide, dacarbazine, procarbizine, prednisolone, dexamethasone, campathecin, plicamycin, asparaginase, aminopterin, methopterin, porfiromycin, melphalan, leurosidine, leurosine, chlorambucil, trabectedin, procarbazine, discodermolide, carminomycin, aminopterin, and hexamethyl melamine, or a combination thereof. In certain embodiments, the compounds described herein or pharmaceutical compositions can be administered in combination with an anti-cancer therapy including, but not limited to, surgery, radiation therapy, transplantation (e.g., stem cell transplantation, bone marrow transplantation), immunotherapy, and chemotherapy.

(502) Also encompassed by the disclosure are kits (e.g., pharmaceutical packs). The kits provided may comprise a pharmaceutical composition or compound described herein and a container (e.g., a vial, ampule, bottle, syringe, and/or dispenser package, or other suitable container). In some embodiments, provided kits may optionally further include a second container comprising a pharmaceutical excipient for dilution or suspension of a pharmaceutical composition or compound described herein. In some embodiments, the pharmaceutical composition or compound described herein provided in the first container and the second container are combined to form one unit dosage form.

(503) Thus, in one aspect, provided are kits including a first container comprising a compound or pharmaceutical composition described herein. In certain embodiments, the kits are useful for treating a disease (e.g., proliferative disease, inflammatory disease, autoimmune disease, CNS disorder, infectious disease, or metabolic disorder) in a subject in need thereof. In certain embodiments, the kits are useful for preventing a disease (e.g., proliferative disease, inflammatory disease, autoimmune disease, CNS disorder, infectious disease, or metabolic disorder) in a subject in need thereof.

(504) In certain embodiments, a kit described herein further includes instructions for using the compound or pharmaceutical composition included in the kit. A kit described herein may also include information as required by a regulatory agency such as the U.S. Food and Drug Administration (FDA). In certain embodiments, the information included in the kits is prescribing information. In certain embodiments, the kits and instructions provide for treating a disease (e.g., proliferative disease, inflammatory disease, autoimmune disease, CNS disorder, infectious disease, or metabolic disorder) in a subject in need thereof. In certain embodiments, the kits and instructions provide for preventing a disease (e.g., proliferative disease, inflammatory disease, autoimmune disease, CNS disorder, infectious disease, or metabolic disorder) in a subject in need thereof. A kit described herein may include one or more additional pharmaceutical agents described herein as a separate composition.

(505) Methods of Treatment and Uses

(506) The present disclosure provides compounds and pharmaceutical compositions useful for inhibiting microorganism growth (e.g., bacterial or parasites). The present invention provides compounds and pharmaceutical compositions useful for killing microorganisms (e.g., bacteria or parasites). The present disclosure also provides methods for the treatment of a wide range of diseases, such as proliferative disease, inflammatory disease, autoimmune disease, CNS disorder, infectious disease, genetic disease, hematological disease, neurological disease, painful condition, psychiatric disorder, and metabolic disorder in a subject in need thereof. The present invention provides methods for the treatment or prevention of a proliferative disease (e.g., cancers (e.g., non-small cell lung cancer, or glioma), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, CNS disorder (e.g., drug addiction), metabolic disorder (e.g., diabetes), and infectious disease (e.g., bacterial infection or parasitic infection (e.g., malaria)) in a subject. In one aspect, the present invention provides methods for inhibiting bacterial growth or killing bacteria comprising administering an effective amount of a compound described herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof), to a subject in need of treatment. In another aspect, the present invention provides methods for treating or preventing an infection (e.g., an infection by a microorganism, a bacterial infection, comprising administering an effective amount of a compound described herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof), to a subject in need of treatment.

(507) In certain embodiments, the effective amount is a therapeutically effective amount. In certain embodiments, the effective amount is a prophylactically effective amount. In certain embodiments, the subject is suffering from an infection (e.g., an infection by a microorganism). In certain embodiments, the subject is suffering from malaria. In certain embodiments, the subject is suffering from a bacterial or parasitic infection. In certain embodiments, the subject is susceptible to having a bacterial or parasitic infection. In certain embodiments, the subject has been exposed or is at risk of being exposed to a pathogenic microorganism. The infection may be prevented or at least the chances of infection may be reduced by the administration of a prophylactic amount of a compound described herein.

(508) In another aspect, the present invention provides a method of killing microorganisms (e.g., bacteria, parasites). In certain embodiments, provided is a method of killing protozoa. In certain embodiments, provided is a method of killing parasites. In another aspect, the present invention provides a method of killing bacteria in a subject comprising administering an effective amount of a compound described herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof. In another aspect, the present invention provides a method of killing parasites in a subject comprising administering an effective amount of a compound described herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

(509) In another aspect, the present invention provides a method of treating and/or preventing a proliferative disease (e.g., cancers (e.g., non-small cell lung cancer, or glioma), inflammatory diseases, autoimmune diseases), CNS disorder (e.g., drug addiction), metabolic disorder (e.g., diabetes), or infectious disease (e.g., bacterial infection or parasitic infection (e.g., malaria)).

(510) In another aspect, provided herein is a method of treating and/or preventing a proliferative disease. In certain embodiments, provided herein is a method of treating and/or preventing cancer. In certain embodiments, provided herein is a method of treating and/or preventing non-small cell lung cancer. In certain embodiments, provided herein is a method of preventing and/or treating brain cancer. In certain embodiments, provided herein is a method of treating and/or preventing glioma. In certain embodiments, provided herein is a method of treating and/or preventing inflammatory disease. In certain embodiments, provided herein is a method of treating and/or preventing autoimmune disease. In certain embodiments, provided herein is a method of treating and/or preventing a CNS disorder. In certain embodiments, provided herein is a method of treating and/or preventing drug addiction. In certain embodiments, provided herein is a method of treating and/or preventing opioid addiction. In certain embodiments, provided herein is a method of treating and/or preventing heroin addiction. In certain embodiments, provided herein is a method of treating and/or preventing addiction to prescription pain relievers (e.g. oxycodone, codeine, morphine). In certain embodiments, provided herein is a method of treating and/or preventing a metabolic disorder. In certain embodiments, provided herein is a method of treating and/or preventing diabetes. In certain embodiments, provided herein is a method of treating and/or preventing an infectious disease. In certain embodiments, provided herein is a method of treating and/or preventing bacterial infection. In certain embodiments, provided herein is a method of treating and/or preventing parasitic infection. In certain embodiments, provided herein is a method of treating and/or preventing malaria.

(511) In certain embodiments, the subject being treated is a mammal. In certain embodiments, the subject is a human. In certain embodiments, the subject is a domesticated animal, such as a dog, cat, cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a companion animal such as a dog or cat. In certain embodiments, the subject is a livestock animal such as a cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a zoo animal. In another embodiment, the subject is a research animal such as a rodent, dog, or non-human primate. In certain embodiments, the subject is a non-human transgenic animal such as a transgenic mouse or transgenic pig.

(512) In certain embodiments, the biological sample being contacted with the compound or composition is breast tissue, bone marrow, lymph node, lymph tissue, spleen, or blood.

(513) In certain embodiments, the cell being contacted with the compound or composition is present in vitro. In certain embodiments, the cell being contacted with the compound or composition is present in vivo. In certain embodiments, the cell being contacted with the compound or composition is present ex vivo. In certain embodiments, the cell being contacted with the compound or composition is a malignant cell (e.g., malignant blood cell). In certain embodiments, the cell being contacted with the compound or composition is a malignant hematopoietic stem cell (e.g., malignant myeloid cell or malignant lymphoid cell). In certain embodiments, the cell being contacted with the compound or composition is a malignant lymphocyte (e.g., malignant T-cell or malignant B-cell). In certain embodiments, the cell being contacted with the compound or composition is a malignant red blood cell, malignant white blood cell, or malignant platelet. In certain embodiments, the cell being contacted with the compound or composition is a malignant neutrophil, malignant macrophage, or malignant plasma cell. In certain embodiments, the cell being contacted with the compound or composition is a carcinoma cell. In certain embodiments, the cell being contacted with the compound or composition is a carcinoma breast cell. In certain embodiments, the cell being contacted with the compound or composition is a sarcoma cell. In certain embodiments, the cell being contacted with the compound or composition is a sarcoma cell from breast tissue.

(514) In certain embodiments, the proliferative disease to be treated or prevented using the compounds described herein is cancer. All types of cancers disclosed herein or known in the art are contemplated as being within the scope of the invention. In certain embodiments, the proliferative disease is a cancer associated with BCL-2 anti-apoptotic proteins (e.g., MCL-1 and/or XIAP) (e.g., cancer associated with dependence on BCL-2 anti-apoptotic proteins). In certain embodiments, the proliferative disease is a cancer associated with overexpression of MYC (a gene that codes for a transcription factor). In certain embodiments, the cancer is a MYC-dependent cancer. In certain embodiments, the proliferative disease is a cancer associated with the amplification of BRCA1. In certain embodiments, the proliferative disease is a cancer associated with the amplification of HER2. In certain embodiments, the proliferative disease is a hematological malignancy. In certain embodiments, the proliferative disease is a blood cancer. In certain embodiments, the proliferative disease is a hematological malignancy. In certain embodiments, the proliferative disease is a leukemia. In certain embodiments, the proliferative disease is chronic lymphocytic leukemia (CLL). In certain embodiments, the proliferative disease is acute lymphoblastic leukemia (ALL). In certain embodiments, the proliferative disease is T-cell acute lymphoblastic leukemia (T-ALL). In certain embodiments, the proliferative disease is chronic myelogenous leukemia (CML). In certain embodiments, the proliferative disease is acute myelogenous leukemia (AML). In certain embodiments, the proliferative disease is acute monocytic leukemia (AMoL). In certain embodiments, the proliferative disease is lymphoma. In some embodiments, the proliferative disease is Burkitt's lymphoma. In certain embodiments, the proliferative disease is a Hodgkin's lymphoma. In certain embodiments, the proliferative disease is a non-Hodgkin's lymphoma. In certain embodiments, the proliferative disease is multiple myeloma. In certain embodiments, the proliferative disease is melanoma. In certain embodiments, the proliferative disease is colorectal cancer. In certain embodiments, the proliferative disease is breast cancer. In certain embodiments, the proliferative disease is recurring breast cancer. In certain embodiments, the proliferative disease is mutant breast cancer. In certain embodiments, the proliferative disease is HER2+ breast cancer. In certain embodiments, the proliferative disease is HER2-breast cancer. In certain embodiments, the proliferative disease is triple-negative breast cancer (TNBC). In certain embodiments, the proliferative disease is a bone cancer. In certain embodiments, the proliferative disease is osteosarcoma. In certain embodiments, the proliferative disease is Ewing's sarcoma. In some embodiments, the proliferative disease is a brain cancer. In some embodiments, the proliferative disease is neuroblastoma. In some embodiments, the proliferative disease is a lung cancer. In some embodiments, the proliferative disease is small cell lung cancer (SCLC). In some embodiments, the proliferative disease is non-small cell lung cancer. In some embodiments, the proliferative disease is a benign neoplasm. All types of benign neoplasms disclosed herein or known in the art are contemplated as being within the scope of the invention. In some embodiments, the proliferative disease is associated with angiogenesis. In some embodiments, the proliferative disease is brain cancer. In some embodiments, the proliferative disease is glioma. All types of angiogenesis disclosed herein or known in the art are contemplated as being within the scope of the invention. In certain embodiments, the proliferative disease is an inflammatory disease. All types of inflammatory diseases disclosed herein or known in the art are contemplated as being within the scope of the invention. In certain embodiments, the inflammatory disease is rheumatoid arthritis.

(515) In certain embodiments, the proliferative disease is an acute inflammatory disease. In certain embodiments, the acute inflammatory disease is rheumatoid arthritis, Crohn's disease, or fibrosis. In some embodiments, the proliferative disease is an autoinflammatory disease. All types of autoinflammatory diseases disclosed herein or known in the art are contemplated as being within the scope of the invention. In some embodiments, the proliferative disease is an autoimmune disease. All types of autoimmune diseases disclosed herein or known in the art are contemplated as being within the scope of the invention.

(516) In certain embodiments, the CNS disorder is drug addiction. In certain embodiments, the drug addiction is opioid addiction. In certain embodiments, the drug addiction is heroin addiction. In certain embodiments, the drug addiction is fentanyl addiction. In certain embodiments, the drug addiction is addiction to prescription pain relievers (e.g. oxycodone, codeine, morphine).

(517) In certain embodiments, the methods described herein include administering to a subject or contacting a biological sample with an effective amount of a compound described herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a pharmaceutical composition thereof. In certain embodiments, the methods described herein include administering to a subject or contacting a biological sample with an effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In certain embodiments, the compound is contacted with a biological sample. In certain embodiments, the compound is administered to a subject. In certain embodiments, the compound is administered in combination with one or more additional pharmaceutical agents described herein. The additional pharmaceutical agent may be an anti-proliferative agent. In certain embodiments, the additional pharmaceutical agent is an anti-cancer agent.

(518) In some embodiments, the additional pharmaceutical agent is a topoisomerase inhibitor, a MCL1 inhibitor, a BCL-2 inhibitor, a BCL-xL inhibitor, a BRD4 inhibitor, a BRCA1 inhibitor, BRCA2 inhibitor, HER1 inhibitor, HER2 inhibitor, a CDK9 inhibitor, a Jumonji histone demethylase inhibitor, or a DNA damage inducer. In some embodiments, the additional pharmaceutical agent is etoposide, obatoclax, navitoclax, JQ1, 4-(((5′-chloro-2′-(((1R,4R)-4-(((R)-1-methoxypropan-2-yl)amino)cyclohexyl)amino)-[2,4′-bipyridin]-6-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile, JIB04, or cisplatin. In some embodiments, the additional pharmaceutical agent is etoposide, obatoclax, or navitoclax, and the disease to be treated is breast cancer, e.g., triple-negative breast cancer, HER2 positive breast cancer, HER2 negative breast cancer, ER-positive breast cancer, ER-negative breast cancer, or ER/PR-positive breast cancer. In some embodiments, the additional pharmaceutical agent is etoposide, JIB04, or cisplatin, and the disease to be treated is Ewing's sarcoma. In some embodiments, the additional pharmaceutical agent is JQ1 or NVP2, and the disease to be treated is leukemia, e.g., acute myelogenous leukemia, myeloblastic leukemia, promyelocytic leukemia, myelomonocytic leukemia, monocytic leukemia, monoblastic leukemia, or megakaryoblastic leukemia. In certain embodiments, a pharmaceutical composition described herein further comprises a combination of the additional pharmaceutical agents described herein.

(519) In certain embodiments, a kit described herein includes a first container comprising a compound or pharmaceutical composition described herein. In certain embodiments, a kit described herein is useful in treating and/or preventing a proliferative disease (e.g., cancers (e.g., non-small cell lung cancer, or glioma), inflammatory diseases, autoimmune diseases), CNS disorder (e.g., drug addiction), metabolic disorder (e.g., diabetes), or infectious disease (e.g., bacterial infection or parasitic infection (e.g., malaria)), in a subject in need thereof.

(520) In certain embodiments, a kit described herein further includes instructions for using the compound or pharmaceutical composition included in the kit. A kit described herein may also include information as required by a regulatory agency such as the U.S. Food and Drug Administration (FDA). In certain embodiments, the information included in the kits is prescribing information. In certain embodiments, the kits and instructions provide for in treating and/or preventing a proliferative disease (e.g., cancers (e.g., non-small cell lung cancer, or glioma), inflammatory diseases, autoimmune diseases), CNS disorder (e.g., drug addiction), metabolic disorder (e.g., diabetes), or infectious disease (e.g., bacterial infection or parasitic infection (e.g., malaria)) in need thereof. A kit described herein may include one or more additional pharmaceutical agents described herein as a separate composition.

(521) Methods of Synthesis

(522) The present disclosure provides methods of synthesizing compounds described herein. In view of the Examples and disclosure provided herein, one of ordinary skill in the art would understand synthetic techniques to synthesize the compounds, including analogs of vincamine, described herein. One of ordinary skill in the art would recognize the synthetic techniques (e.g., standard organic synthetic reactions) to synthesize analogs of vincamine based on the Examples and disclosure provided herein.

EXAMPLES

(523) In order that the disclosure may be more fully understood, the following examples are set forth. The examples described in this application are offered to illustrate the compounds, pharmaceutical compositions, uses, and methods provided herein and are not to be construed in any way as limiting their scope.

(524) All reactions were carried out under an atmosphere of argon unless otherwise specified. Anhydrous solvents were transferred via syringe to flame-dried glassware, which was cooled under a stream of dry argon. Anhydrous tetrahydrofuran, and all chemical reagents for synthesis were used without further purification. Analytical thin layer chromatography (TLC) was performed using 250 μm Silica Gel 60 F254 pre-coated plates (EMD Chemicals Inc.). Flash column chromatography was performed using 230-400 Mesh 60 Å Silica Gel (Sorbent Technologies).

(525) .sup.1H NMR experiments were recorded on a Varian Unity spectrometer (at 400 MHz), Agilent/Varian VNMRS-600 spectrometer (at 600 MHz), or Avance II spectrometer (at 600 MHz). .sup.13C NMR experiments were recorded on a Varian Unity spectrometer (at 400 MHz), Agilent/Varian VNMRS-600 spectrometer (at 150 MHz), or Avance II spectrometer (at 150 MHz). Spectra were obtained in the following solvents (reference peaks also included for .sup.1H and .sup.13C NMRs): CDCl.sub.3 (.sup.1H NMR: 7.26 ppm; .sup.13C NMR: 77.23 ppm), d.sub.6-DMSO (.sup.1H NMR: 2.50 ppm; .sup.13C NMR: 39.52 ppm), CD.sub.3CN (.sup.1H NMR: 1.94 ppm; .sup.13C: 1.32 ppm). NMR samples where the respective solvent peaks were buried in the sample signals referenced TMS at 0.00 ppm for .sup.1H NMR experiments. NMR experiments were performed at room temperature unless otherwise indicated. Chemical shift values (δ) are reported in parts per million (ppm) for all .sup.1H NMR and .sup.13C NMR spectra. H NMR multiplicities are reported as: s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet.

EXPERIMENTAL PROCEDURES

Example 1. Chemical Synthesis and Characterization of Selected Compounds

(526) Chemical Synthesis and Characterization

(527) ##STR00125##

(528) .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.48 (m, 1H), 7.16-7.07 (m, 3H), 4.59 (s, 1H), 3.91 (s, 1H), 3.82 (s, 3H), 3.41-3.22 (m, 2H), 2.99 (m, 1H), 2.67-2.45 (m, 3H), 2.32-2.18 (m, 2H), 2.12 (d, 1H), 1.82-1.58 (m, 3H), 1.53-1.31 (m, 3H), 0.91 (t, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 174.7, 134.3, 131.6, 129.2, 121.8, 120.4, 118.7, 110.5, 106.1, 82.1, 59.4, 54.5, 51.2, 44.8, 44.6, 35.3, 29.1, 25.3, 21.0, 17.1, 7.8.

(529) ##STR00126##

(530) Procedure for the synthesis of V14: V (51.6 mg, 0.146 mmol) was added to a round-bottom flask and dissolved in a 40 μM methylene blue solution (12.1 mL). The round-bottom flask was placed in a dewar and irradiated with a 627 nm 3 W LED. The reaction proceeded for 24 hours, concentrated in vacuo, and crude product was purified via column chromatography using a gradient of dichloromethane 100% to dichloromethane:methanol 99:1 to yield V14 (19.9 mg, 35%) as a white solid. Note: V14 is a known compound (CAS No. 59373-44-3), the spectral data below were consistent with literature..sup.1 1H NMR: (600 MHz, CDCl.sub.3) δ 7.70 (d, J=8.1 Hz, 1H), 7.46 (dd, J=7.4, 1.2 Hz, 1H), 7.46 (td, J=7.7, 1.6 Hz, 1H), 7.23 (td, J=7.7, 0.9 Hz, 1H), 4.33 (s, 1H), 3.60 (s, 3H), 3.39 (dd, J=13.3, 5.9 Hz, 1H), 3.33 (d, J=13.3 Hz, 1H), 3.09 (ddd, J=14.0, 6.1 Hz, 1H), 2.97-2.90 (m, 2H), 2.71 (s, 1H), 2.62 (td, J=12.9, 1.3 Hz, 1H), 2.47 (td, J=11.8, 2.7 Hz, 1H), 2.02 (sextet, J=7.3 Hz, 1H), 1.82 (qt, J=13.2, 4.6 Hz, 1H), 1.70 (dd, J=13.8, 2.5 Hz, 1H), 1.65 (d, J=13.3 Hz, 1H), 1.54 (dq, J=13.9, 2.2 Hz, 1H), 1.30 (sextet, J=7.3 Hz, 1H), 1.14 (td, J=13.9, 5.5 Hz, 1H), 0.96 (t, J=7.3 Hz, 3H). .sup.13C NMR: (150 MHz, CDCl.sub.3) δ 204.4, 173.2, 173.0, 138.9, 137.7, 131.9, 129.1, 126.5, 122.3, 89.4, 74.5, 56.8, 54.2, 53.5, 43.7, 37.7, 37.1, 33.0, 30.9, 22.5, 7.8. HRMS (ESI): calc. for C.sub.21H.sub.27N.sub.2O.sub.5 [M+H].sup.+: 387.1914, found: 387.1928.

(531) ##STR00127##

(532) Procedure for the synthesis of V13: V (317.1 mg, 0.895 mmol) was added to a round-bottom flask and dissolved in a 2:1 solution of saturated aqueous sodium bicarbonate:chloroform (19.0 mL). Iodine (965.1 mg, 3.80 mmol) was added to the reaction, which proceeded for 6 hours. At this time, the reaction was quenched with saturated sodium thiosulfate, extracted with ethyl acetate, extract dried with sodium sulfate, and the organic layer was concentrated in vacuo. The crude product was purified via column chromatography using a gradient of 100% hexanes to 3:1 hexanes:ethyl acetate with 1% triethylamine throughout to afford V13 (331.4 mg, 77%) as a white-yellow solid. Note: V14 is a known compound (CAS No. 74947-45-8). .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.38 (m, 1H), 7.12 (td, J=7.0, 6.2, 3.6 Hz, 2H), 6.98 (m, 1H), 6.29 (s, 1H), 4.29 (s, 2H), 4.04 (s, 3H), 3.58 (dd, J=14.1, 7.2 Hz, 1H), 3.26 (ddd, J=14.1, 11.0, 6.4 Hz, 1H), 2.84 (d, J=12.0 Hz, 1H), 2.75 (dddd, J=18.4, 11.0, 7.6, 1.5 Hz, 1H), 2.61 (dd, J=16.4, 6.2 Hz, 1H), 2.42 (d, J=12.0 Hz, 1H), 1.73 (sextet, J=7.5 Hz, 1H), 1.49 (sextet, J=7.5 Hz, 1H), 1.01 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 168.8, 143.2, 137.7, 135.1, 131.1, 122.9, 121.3, 118.6, 112.0, 111.6, 91.1, 85.4, 63.0, 53.5, 53.3, 49.9, 45.8, 45.7, 25.0, 21.5, 9.3. HRMS (ESI): calc. for C.sub.21H.sub.22IN.sub.2O.sub.3 [M+H]+: 477.0670, found: 477.0661. MP: 173-175° C., decomposed, lit. 173-175° C., decomposed..sup.2

(533) ##STR00128##

(534) General Procedure for the synthesis of V15, V47-V49: To a flame-dried round-bottom flask was added V13 (32.0 mg, 0.067 mmol), trans-phenylboronic acid (10.4 mg, 0.071 mmol), and potassium carbonate (27.9 mg, 0.202 mmol). Methanol (2.0 mL) was added, then a 0.04 M solution of Pd(OAc).sub.2 (4.5 mg, 0.020 mmol) in methanol was added dropwise at room temperature. The resulting reaction mixture was heated to reflux for 3 hours, cooled to room temperature, quenched with 1 M HCl, extracted with ethyl acetate, organics were washed with brine. The organics were dried with sodium sulfate, filtered, and concentrated in vacuo. Then crude product purified via column chromatography using a gradient of 100% hexanes to 3:1 hexanes:ethyl acetate with 1% triethylamine throughout to afford V15 (26.8 mg, 88%) as a colorless solid.

(535) ##STR00129##

(536) Yield: 88%; 26.8 mg of V15 isolated as a colorless solid. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.35 (m, 1H), 7.27-7.22 (m, 2H), 7.17 (dd, J=7.4 Hz, 2H), 7.11-7.01 (m, 3H), 6.96 (m, 1H), 6.49 (d, J=16.1 Hz, 1H), 6.28 (d, J=16.1 Hz, 1H), 6.07 (s, 1H), 4.53 (d, J=1.8 Hz, 1H), 4.39 (s, 1H), 4.06 (s, 3H), 3.70 (dd, J=14.1, 7.4 Hz, 1H), 3.50 (ddd, J=14.1, 10.9, 6.5 Hz, 1H), 2.92-2.77 (m, 2H), 2.70 (ddd, J=16.3, 6.5, 1.6 Hz, 1H), 2.49 (d, J=12.0 Hz, 1H), 1.70 (sextet, J=7.5 Hz, 1H), 1.50 (sextet, J=7.5 Hz, 1H), 1.05 (t, J=7.5 Hz, 3H). Note: .sup.1H spectrum referenced TMS at 0.00 ppm. .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 169.3, 138.6, 138.3, 137.9, 136.0, 131.3, 129.4, 128.5, 126.0, 125.7, 122.8, 121.7, 121.3, 118.6, 112.7, 112.1, 111.7, 91.7, 77.4, 54.9, 53.5, 50.4, 45.5, 43.8, 25.1, 21.8, 9.5. Note: The presence of a carbon at 77.4 was proven by HSQC. HRMS (ESI): calc. for C.sub.29H.sub.28N.sub.2O.sub.3 [M+H].sup.+: 453.2173, found: 453.2162. MP: 225-227° C., decomposed.

(537) ##STR00130##

(538) Yield: 40%; 15.7 mg of V47 isolated as a yellow residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) 7.33 (dd, J=6.6, Hz, 1H), 7.26 (d, J=8.3, 2H), 7.15 (dd, J=7.8 Hz, 2H), 7.11-6.93 (m, 4H), 6.41 (s, 1H), 4.47 (d, J=1.8 Hz, 1H), 4.42 (s, 1H), 4.07 (s, 3H), 3.76 (dd, J=14.1, 7.3 Hz, 1H), 3.55 (ddd, J=14.1, 11.0, 6.5 Hz, 1H), 2.90-2.77 (m, 2H), 2.70 (ddd, J=16.4, 6.5, 1.9 Hz, 1H), 2.48 (d, J=12.0 Hz, 1H), 1.74 (sextet, J=7.5 Hz, 1H), 1.49 (sextet, J=7.5 Hz, 1H), 1.05 (t, J=7.5 Hz, 3H). Note: .sup.1H spectrum referenced TMS at 0.00 ppm. .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 169.4, 140.2, 138.1, 136.2, 134.6, 131.5, 128.5, 125.2, 124.4, 122.8, 121.3, 118.6, 112.1, 111.9, 111.8, 91.6, 80.1, 54.5, 53.5, 50.6, 45.4, 43.9, 25.1, 21.7, 9.5. HRMS (ESI): calc. for C.sub.27H.sub.27N.sub.2O.sub.3 [M+H].sup.+: 427.2016, found: 427.2002.

(539) ##STR00131##

(540) Yield: 72%; 27.0 mg of V48 isolated as a colorless residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.34 (dd, J=6.4, 2.0 Hz, 1H), 7.13-7.03 (m, 3H), 6.98 (dd, J=6.4, 2.0 Hz, 1H), 6.88 (d, J=8.1 Hz, 1H), 6.82 (dd, J=2.1 Hz, 1H), 6.59 (dd, J=8.1, 2.5 Hz, 1H), 6.43 (s, 1H), 4.47 (d, J=1.8 Hz, 1H), 4.42 (s, 1H), 4.07 (s, 3H), 3.80-3.71 (m, 4H), 3.54 (ddd, J=14.1, 11.0, 6.5 Hz, 1H), 2.91-2.78 (m, 2H), 2.71 (ddd, J=16.3, 6.3, 1.9 Hz, 1H), 2.49 (d, J=12.0 Hz, 1H), 1.74 (sextet, J=7.5 Hz, 1H), 1.50 (sextet, J=7.5 Hz, 1H), 1.06 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 169.3, 159.8, 141.7, 138.1, 136.2, 134.8, 131.5, 129.4, 122.7, 121.2, 118.6, 117.1, 112.0 (2C), 111.6, 110.4, 110.2, 91.6, 80.0, 55.3, 54.4, 53.4, 50.5, 45.4, 43.9, 25.1, 21.8, 9.4. HRMS (ESI): calc. for C.sub.28H.sub.29N.sub.2O.sub.4 [M+H].sup.+: 457.2122, found: 457.2102.

(541) ##STR00132##

(542) Yield: 66%; 22.5 mg of V49 isolated as a colorless residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.33 (dd, J=6.4, 2.1 Hz, 1H), 7.19 (d, J=8.4 Hz, 2H), 7.11-7.02 (m, 2H), 6.96 (dd, J=6.4, 2.1 Hz, 1H), 6.74 (d, J=8.4 Hz, 2H), 6.31 (s, 1H), 4.45 (d, J=1.8 Hz, 1H), 4.42 (s, 1H), 4.07 (s, 3H), 3.84-3.77 (m, 4H), 3.74 (dd, J=14.1, 7.2 Hz, 1H), 3.53 (ddd, J=14.4, 11.1, 6.6 Hz, 1H), 3.07-2.95 (m, 4H), 2.90-2.77 (m, 2H), 2.70 (ddd, J=16.3, 6.3, 1.6 Hz, 1H), 2.48 (d, J=12.0 Hz, 1H), 1.75 (sextet, J=7.5 Hz, 1H), 1.49 (sextet, J=7.5 Hz, 1H), 1.05 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 169.4, 149.2, 138.0, 136.2, 133.1, 132.4, 131.5, 125.2, 122.7, 121.2, 118.6, 116.1, 112.0, 111.9, 111.7, 91.5, 80.2, 67.1, 54.5, 53.4, 50.5, 49.9, 45.5, 43.9, 25.1, 21.6, 9.5. HRMS (ESI): calc. for C.sub.31H.sub.34N.sub.3O.sub.4 [M+H].sup.+: 512.2544, found: 512.2550.

(543) ##STR00133##

(544) General Procedure for the synthesis of V16-V17: To a flame-dried round-bottom flask was added V13 (58.5 mg, 0.123 mmol), Bis(triphenylphosphine)palladium(II) dichloride (17.2 mg, 0.025 mmol), and copper(I) iodide (9.4 mg, 0.049 mmol). Phenylacetylene (20.0 μL, 0.184 mmol) was added dropwise, and the resulting dry materials were dissolved in a 2:1 diethylamine:anhydrous N,N-dimethylformamide solution (1.2 mL). The reaction was heated to 60° C. and proceeded for thirty-minutes. At this time, the reaction was quenched with deionized water, washed with 1 M HCl, and extracted with ethyl acetate. Crude extract was filtered through a plug of celite, dried with sodium sulfate, filtered, and concentrated in vacuo. Crude product purified via column chromatography using a gradient of 100% hexanes to 5:1 hexanes:ethyl acetate with 1% triethylamine to afford V16 (16.6 mg, 30%) as a brown resin.

(545) ##STR00134##

(546) Yield: 30%; 16.6 mg of V16 isolated as a brown residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.39 (m, 1H), 7.30-7.25 (m, 2H), 7.23-7.05 (m, 5H), 6.98 (m, 1H), 6.43 (s, 1H), 4.43 (s, 1H), 4.35 (d, J=1.8 Hz, 1H), 4.07 (s, 3H), 3.74 (dd, J=14.4, 7.4 Hz, 1H), 3.54 (ddd, J=14.1, 11.2, 6.7 Hz, 1H), 2.91 (m, 1H), 2.82 (d, J=12.0 Hz, 1H), 2.74 (ddd, J=16.3, 6.5, 1.7 Hz, 1H), 2.49 (d, J=12.0 Hz, 1H), 1.73 (sextet, J=7.5 Hz, 1H), 1.54 (sextet, J=7.5 Hz, 1H), 1.06 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 169.1, 143.4, 137.9, 135.5, 131.3, 131.1, 128.2, 127.1, 124.4, 123.0, 121.4, 118.7, 112.1, 112.0, 94.4, 91.5, 90.6, 87.0, 80.2, 54.1, 53.6, 50.5, 45.4, 43.8, 24.9, 22.0, 9.4. HRMS (ESI): calc. for C.sub.29H.sub.27N.sub.2O.sub.3 [M+H].sup.+: 451.2016, found: 451.2035.

(547) ##STR00135##

(548) Yield: 12%; 7.2 mg of V17 isolated as a pinkish-red residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.38 (m, 1H), 7.22 (d, J=8.5 Hz, 2H), 7.15-7.07 (m, 2H), 6.98 (m, 1H), 6.73 (d, J=8.5 Hz, 2H), 6.39 (s, 1H), 4.42 (s, 1H), 4.33 (d, J=1.9 Hz, 1H), 4.06 (s, 3H), 3.77-3.69 (m, 4H), 3.54 (ddd, J=14.1, 11.3, 6.4 Hz, 1H), 2.91 (m, 1H), 2.81 (d, J=12.0 Hz, 1H), 2.74 (ddd, J=16.2, 6.0, 1.5 Hz, 1H), 2.49 (d, J=12.0 Hz, 1H), 1.73 (sextet, J=7.5 Hz, 1H), 1.51 (m, 1H), 1.06 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 169.1, 158.8, 142.8, 137.9, 135.6, 132.6, 131.4, 123.0, 121.4, 118.7, 116.6, 113.9, 112.1, 112.0, 94.8, 91.5, 88.9, 86.6, 80.3, 55.4, 54.1, 53.6, 50.5, 45.5, 43.8, 24.9, 22.0, 9.4. HRMS (ESI): calc. for C.sub.30H.sub.29N.sub.2O.sub.4 [M+H].sup.+: 481.2122, found: 481.2142.

(549) ##STR00136##

(550) Procedure for the synthesis of V35: V (802.1 mg, 2.26 mmol) was added to a flame-dried microwave flask and dissolved in N,N-dimethylformamide (17.5 mL). A 3.0 M solution of cyanogen bromide in dichloromethane (2.30 mL, 6.79 mmol) was added dropwise to the resulting solution. The reaction was subjected to microwave irradiation at 100° C. for three minutes. The reaction was cooled to room temperature, diluted with ethyl acetate, and quenched with brine (3×100 mL). The organic layer was dried with sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified via column chromatography using a gradient of 100% chloroform to 24:1 chloroform:acetone to yield V35 (520.0 mg, 50%) as a white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.56 (m, 1H), 7.26 (m, 1H), 7.22-7.12 (m, 2H), 4.77 (s, 1H), 4.31 (s, 1H), 3.72-3.59 (m, 5H), 3.51-3.34 (m, 2H), 3.28-3.13 (m, 2H), 2.45 (d, J=15.0 Hz, 1H), 2.25 (d, J=15.0 Hz, 1H), 1.92 (m, 1H), 1.73-1.50 (m, 4H), 1.46 (ddd, J=14.1, 8.4, 4.3 Hz, 1H), 0.80 (t, J=7.4 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 173.0, 135.5, 128.5, 128.2, 123.6, 121.1, 119.0, 118.2, 114.2, 111.8, 82.4, 59.8, 54.2, 48.0, 40.9, 36.3, 32.3, 29.9, 29.1, 28.5, 19.9, 7.4. HRMS (ESI): calc. for C.sub.22H.sub.26BrN.sub.3O.sub.3 [M+Na].sup.+: 482.1050, found: 482.1071. MP: 155-157° C.

(551) ##STR00137##

(552) Procedure for the synthesis of V36: V35 (203.0 mg, 0.441 mmol) was added to a flame-dried microwave flask and dissolved in N,N-dimethylformamide (4.41 mL). Sodium azide (229.5 mg, 3.53 mmol) was added to the resulting solution. The reaction was subjected to microwave irradiation at 100° C. for four minutes. The reaction was cooled to room temperature, diluted with ethyl acetate, and quenched with brine (3×50 mL). The organic layer was dried with sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified via column chromatography using a gradient of 100% chloroform to 49:1 chloroform:acetone to yield V36 (111.4 mg, 60%) as a white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.57 (m, 1H), 7.24-7.11 (m, 3H), 4.73 (s, 1H), 4.19 (d, J=1.4 Hz, 1H), 3.82 (s, 3H), 3.72 (ddd, J=12.2, 7.0, 5.8 Hz, 1H), 3.64-3.52 (m, 2H), 3.25 (td, J=12.6, 3.0 Hz, 1H), 3.10 (ddd, J=8.5, 6.7, 1.8 Hz, 2H), 2.98 (m, 1H), 1.97-1.82 (m, 3H), 1.75-1.63 (m, 2H), 1.43 (td, J=14.2, 6.5 Hz, 1H), 1.18 (sextet, J=7.4 Hz, 1H), 0.91 (t, J=7.4 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 174.6, 135.0, 128.4, 128.0, 123.8, 120.9, 119.6, 116.5, 114.3, 111.4, 82.2, 57.8, 54.8, 51.6, 51.0, 35.4, 35.1, 32.9, 30.1, 24.5, 20.4, 7.3. HRMS (ESI): calc. for C.sub.22H.sub.26N.sub.6O.sub.3 [M+Na].sup.+: 445.1959, found: 445.1979. MP: 127-129° C.

(553) ##STR00138##

(554) General Procedure for the synthesis of V37-V41: Anhydrous copper sulfate (4.6 mg, 0.03 mmol) and sodium ascorbate (16.6 mg, 0.08 mmol) were added to a vial and dissolved in a solution of tert-butanol:H.sub.2O (1:2). The resultant solution was added to a round-bottom flask containing V36 (24.1 mg, 0.06 mmol). Phenylacetylene (18.8 μL, 0.17 mmol) was added dropwise to the reaction as a 0.3 M solution in dichloromethane. The reaction was vigorously stirred at room temperature for 1.5 hours, upon completion, the biphasic mixture was quenched with brine. The crude reaction mixture was extracted with dichloromethane, the organic layer was dried with sodium sulfate, filtered, and concentrated in vacuo. Crude product was purified via column chromatography using a gradient of 100% dichloromethane to 99:1 dichloromethane:methanol to afford V38 (27.0 mg, 90%) as a yellow residue.

(555) ##STR00139##

(556) Yield: 79%; 22.7 mg of V37 isolated as a purple residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.54 (m, 1H), 7.25-7.14 (m, 6H), 6.98 (dd, J=5.1, 3.6 Hz, 1H), 4.91 (ddd, J=13.6, 6.2, 4.2 Hz, 1H), 4.71-4.60 (m, 2H), 3.80 (s, 3H), 3.77 (d, J=1.1 Hz, 1H), 3.64-3.49 (m, 2H), 3.44 (ddd, J=15.3, 6.3, 4.1 Hz, 1H), 3.19 (td, J=12.6, 3.1 Hz, 1H), 2.85 (d, J=14.4 Hz, 1H), 1.86-1.71 (m, 3H), 1.67-1.54 (m, 2H), 1.38-1.21 (m, 2H), 0.74-0.55 (m, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 174.4, 142.6, 135.1, 133.0, 128.7, 127.9, 127.6, 125.0, 124.2, 124.0, 121.2, 120.7, 119.3, 116.6, 113.3, 111.5, 82.2, 57.7, 54.8, 50.8, 50.4, 34.8 (2C), 32.8, 30.2, 26.1, 20.3, 7.1. HRMS (ESI): calc. for C.sub.28H.sub.31N.sub.6O.sub.3S [M+H].sup.+: 531.2173, found: 531.2155.

(557) ##STR00140##

(558) Yield: 90%; 27.0 mg of V38 isolated as a white-yellow solid. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.68-7.62 (m, 2H), 7.54 (m, 1H), 7.38-7.30 (m, 3H), 7.27 (m, 1H), 7.25-7.11 (m, 3H), 4.93 (ddd, J=13.6, 6.2, 4.0 Hz, 1H), 4.72 (s, 1H), 4.66 (ddd, J=13.6, 6.2, 4.0 Hz, 1H), 3.79 (s, 3H), 3.76 (s, 1H), 3.63-3.49 (m, 2H), 3.46 (ddd, J=14.9, 5.8, 4.3 Hz, 1H), 3.19 (td, J=12.6, 3.0 Hz, 1H), 2.83 (d, J=14.3 Hz, 1H), 1.86-1.69 (m, 3H), 1.59 (m, 1H), 1.36-1.18 (m, 3H), 0.70-0.52 (m, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 174.5, 147.5, 135.0, 130.6, 128.9, 128.6, 128.1, 127.9, 125.8, 124.0, 121.2, 121.2, 119.3, 116.6, 113.4, 111.5, 82.1, 57.7, 54.8, 50.8, 50.3, 34.8, 34.7, 32.8, 30.2, 26.2, 20.3, 7.0. HRMS (ESI): calc. for C.sub.30H.sub.33N.sub.6O.sub.3 [M+H].sup.+: 525.2609, found: 525.2585. MP: 118-120° C.

(559) ##STR00141##

(560) Yield: 91%; 18.2 mg of V39 isolated as a white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.64 (m, 1H), 7.54-7.46 (m, 2H), 7.34 (s, 1H), 7.29-7.12 (m, 5H), 4.94 (ddd, J=13.5, 6.1, 4.1 Hz, 1H), 4.73-4.61 (m, 2H), 3.81 (s, 3H), 3.78 (d, J=1.1 Hz, 1H), 3.62-3.50 (m, 2H), 3.44 (m, 1H), 3.20 (td, J=12.7, 3.3 Hz, 1H), 2.85 (d, J=14.3 Hz, 1H), 1.86-1.73 (m, 3H), 1.69-1.57 (m, 2H), 1.36-1.19 (m, 2H), 0.68-0.57 (m, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 174.4, 146.4, 135.2, 135.0, 132.7, 130.2, 128.6, 128.2, 128.1, 126.1, 124.1, 124.0, 121.6, 121.3, 119.3, 116.6, 113.5, 111.6, 82.4, 57.9, 54.7, 51.0, 50.5, 35.2, 35.0, 33.0, 30.3, 26.2, 20.4, 7.1. HRMS (ESI): calc. for C.sub.30H.sub.31CIN.sub.6O.sub.3 [M+Na].sup.+: 581.2038, found: 581.2030. MP: 101-103° C.

(561) ##STR00142##

(562) Yield: 54%; 17.4 mg of V40 isolated as a clear residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.40 (d, J=7.8 Hz, 1H), 7.22-7.09 (m, 3H), 6.97 (s, 1H), 4.79 (ddd, J=13.6, 6.9, 4.3 Hz, 1H), 4.71 (s, 1H), 4.57 (ddd, J=13.6, 9.6, 6.5 Hz, 1H), 3.94 (d, J=1.7 Hz, 1H), 3.81 (s, 3H), 3.64-3.51 (m, 2H), 3.36 (ddd, J=15.2, 6.2, 4.0 Hz, 1H), 3.23 (td, J=12.9, 2.3 Hz, 1H), 3.04 (pentet, J=7.7 Hz, 1H), 2.90 (d, J=14.3 Hz, 1H), 2.05-1.74 (m, 5H), 1.67-1.26 (m, 9H), 0.93-0.79 (m, 4H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 174.4, 152.5, 135.1, 128.4, 128.3, 123.9, 121.2, 121.1, 119.4, 116.6, 113.9, 111.5, 82.4, 57.9, 54.6, 51.0, 50.2, 36.9, 35.4, 35.0, 33.4, 33.3, 33.0, 30.1 (2C), 25.9, 25.3, 20.5, 7.3. HRMS (ESI): calc. for C.sub.29H.sub.36N.sub.6O.sub.3Na [M+Na].sup.+: 539.2741, found: 539.2766.

(563) ##STR00143##

(564) Yield: 70%; 21.6 mg of V41 isolated as a yellow residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.39 (d, J=7.7 Hz, 1H), 7.23-7.07 (m, 3H), 7.05 (s, 1H), 4.86-4.74 (m, 2H), 4.63 (m, 1H), 3.95 (s, 1H), 3.80 (s, 3H), 3.62-3.45 (m, 4H), 3.37 (m, 1H), 3.23 (td, J=12.6, 2.9 Hz, 1H), 2.91 (d, J=14.3 Hz, 1H), 2.66-2.54 (m, 2H), 1.94-1.76 (m, 3H), 1.73-1.54 (m, 5H), 1.51-1.29 (m, 4H), 0.98-0.82 (m, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 174.4, 147.5, 134.9, 128.4, 128.2, 123.9, 122.6, 121.1, 119.3, 116.7, 113.6, 111.4, 82.2, 62.5, 57.7, 54.8, 50.8, 50.2, 35.0, 34.9, 32.9, 32.1, 30.0, 26.0, 25.3, 25.2, 20.3, 7.4. HRMS (ESI): calc. for C.sub.28H.sub.36N.sub.6O.sub.4Na [M+Na].sup.+: 534.2690, found: 543.2726.

(565) ##STR00144##

(566) General Procedure for the synthesis of V1-V3, V18, V27-V31, & V34: V (106.0 mg, 0.300 mmol) was added to a flame-dried round-bottom flask and dissolved in a 2.5:1.0 (THF:H.sub.2) solution (30 mL). Methyl propiolate (40 μL, 0.449 mmol) was added dropwise and the reaction was stirred at room temperature. The reaction was heated to 66° C. for 3.5 hours, after this time, the reaction was cooled to room temperature and quenched with brine (2×50 mL). The reaction mixture was diluted with ethyl acetate, extracted, dried with sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified via column chromatography using a gradient of 100% hexanes to 1:1 hexanes:ethyl acetate to afford V18 (51.7 mg, 38%) as a white solid. Note: The presence of two carbon signals at ˜22.0 ppm for V1-V3, V18, V27-V31 &V34 was proven by HSQC with V27 & V29.

(567) ##STR00145##

(568) Yield: 38%; 51.7 mg of V27 isolated as a white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.56 (d, J=13.3 Hz, 1H), 7.51 (dd, J=7.3, 1.2 Hz 1H), 7.23-7.18 (m, 2H), 7.15 (m, 1H), 4.84-4.73 (m, 2H), 4.66 (s, 1H), 3.83 (s, 3H), 3.74-3.63 (m, 4H), 3.50 (dd, J=14.1, 7.2 Hz, 1H), 3.16 (td, J=14.9, 12.0, 2.1 Hz, 1H), 2.88 (m, 2H), 2.78 (d, J=14.2 Hz, 1H), 2.27 (dd, J=14.2, 8.8 HZ, 1H), 1.98-1.84 (m, 3H), 1.83-1.66 (m, 2H), 1.63 (m, 1H), 1.53 (m, 1H), 1.29 (dd, J=15.8, 7.8 Hz, 1H), 0.89 (td, J=7.6, 1.2 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 174.6, 169.8, 151.0, 136.0, 135.3, 128.3, 123.2, 120.7, 118.8, 112.1, 111.8, 87.3, 83.0, 66.5, 58.9, 56.8, 54.4, 50.7, 40.8, 40.0, 33.1, 27.0, 21.8 (2C), 8.0. HRMS (ESI): calc. for C.sub.25H.sub.32N.sub.2O.sub.6Na [M+Na].sup.+: 479.2153, found: 479.2140. MP: 178-180° C.

(569) ##STR00146##

(570) Yield: 73%; 101.3 mg of V18 isolated as a white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.60 (d, J=13.3 Hz, 1H), 7.53 (m, 1H), 7.25-7.13 (m, 3H), 4.83 (d, J=13.3 Hz, 1H), 4.69 (s, 1H), 4.22 (s, 1H), 3.81 (s, 3H), 3.72 (m, 4H), 3.52 (dd, J=13.9, 6.9 Hz, 1H), 3.24-3.20 (m, 4H), 2.95 (dd, J=16.0, 1.8 Hz, 1H), 2.88 (t, J=14.0, 12.2 Hz, 1H), 2.76 (d, J=13.8 Hz, 1H), 2.29 (ddd, J=14.1, 9.4, 1.7 Hz, 1H), 1.92-1.67 (m, 4H), 1.65-1.48 (m, 2H), 1.36-1.23 (m, 2H), 0.87 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 174.7, 169.7, 150.8, 135.5, 133.4, 128.1, 123.0, 120.5, 118.4, 113.4, 112.2, 87.0, 83.1, 75.3, 59.3, 56.7, 56.2, 54.1, 50.7, 41.0, 40.6, 33.2, 27.2, 22.0 (2C), 8.0. MP: 205-207° C., lit. 205° c..sup.3

(571) ##STR00147##

(572) Yield: 78%; 110.0 mg of V1 as a yellow residue. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.60 (d, J=13.3 Hz, 1H), 7.52 (dd, J=8.3, 1.6 Hz 1H), 7.24-7.11 (m, 3H), 4.82 (d, J=13.3 Hz, 1H), 4.65 (s, 1H), 4.30 (s, 1H), 3.81 (s, 3H), 3.74-3.66 (m, 4H), 3.52 (dd, J=13.9, 6.9 Hz, 1H), 3.45-3.31 (m, 2H), 3.19 (dd, J=13.6 Hz, 1H), 2.95-2.81 (m, 3H), 2.28 (dd, J=14.8, 8.4 Hz, 1H), 1.92-1.80 (m, 3H), 1.74 (m, 1H), 1.64-1.49 (m, 2H), 1.28 (m, 1H), 1.12-1.03 (t, J=6.9 Hz, 3H), 0.87 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 174.8, 169.7, 150.8, 135.5, 134.2, 128.1, 122.9, 120.4, 118.4, 112.9, 112.2, 87.0, 83.2, 73.2, 63.3, 59.2, 56.7, 54.1, 50.7, 40.9, 40.8, 33.2, 27.2, 22.0 (2C), 15.3, 8.0. HRMS (ESI): calc. for C.sub.27H.sub.37N.sub.2O.sub.6 [M+H].sup.+: 485.2646, found: 485.2655.

(573) ##STR00148##

(574) Yield: 15%; 20.9 mg of V28 as a yellow residue. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.60-7.46 (m, 2H), 7.23-7.12 (m, 2H), 7.10 (dd, J=7.3, 1.0 Hz, 1H), 4.76 (m, 2H), 4.30 (s, 1H), 3.83 (s, 1H), 3.76-3.65 (m, 4H), 3.49-3.27 (m, 3H), 3.12 (m, 1H), 3.03-2.96 (m, 2H), 2.53 (m, 1H), 2.45 (d, J=14.6 Hz, 1H), 2.28 (d, J=14.6 Hz, 1H), 1.89 (sextet, J=14.6, 7.3 Hz, 1H), 1.73-1.57 (m, 4H), 1.36 (m, 1H), 1.09 (t, J=7.0 Hz, 1H), 0.88 (t, J=7.5 Hz, 1H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 172.3, 169.8, 151.5, 135.6, 134.0, 127.7, 123.1, 120.4, 118.6, 112.5, 111.1, 86.8, 82.4, 74.5, 64.0, 58.2, 56.3, 53.6, 50.7, 46.1, 41.9, 34.0, 29.4, 22.4 (2C), 15.2, 8.1. HRMS (ESI): calc. for C.sub.27H.sub.36N.sub.2O.sub.6Na [M+Na].sup.+: 507.2466, found: 507.2486.

(575) ##STR00149##

(576) Yield: 25%; 35.7 mg of V2 as a clear-brown residue. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.61 (d, J=13.3 Hz, 1H), 7.51 (dd, J=7.2, 1.0 Hz, 1H), 7.22-7.12 (m, 3H), 4.82 (d, J=13.3 Hz, 1H), 4.55 (s, 1H), 4.40 (s, 1H), 3.80 (s, 3H), 3.75-3.67 (m, 4H), 3.59-3.47 (m, 2H), 3.16 (dd, J=13.8 Hz, 1H), 3.00-2.81 (m, 3H), 2.30 (dd, J=13.8, 9.2 Hz, 1H), 1.93-1.70 (m, 4H), 1.60-1.49 (m, 2H), 1.22 (dd, J=15.9, 7.9 Hz, 1H), 1.14 (d, J=6.0 Hz, 3H), 0.90 (d, J=6.1 Hz, 3H), 0.86 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 175.0, 169.7, 150.6, 135.6, 135.2, 128.3, 122.9, 120.5, 118.4, 112.6, 112.3, 87.3, 83.2, 70.3, 67.5, 59.4, 56.7, 54.0, 50.7, 41.0, 40.9, 33.2, 27.3, 23.7, 22.0 (2C), 21.3, 8.1. HRMS (ESI): calc. for C.sub.27H.sub.36N.sub.2O.sub.6Na [M+Na].sup.+: 521.2622, found: 521.2630.

(577) ##STR00150##

(578) Yield: 60%; 84.4 mg of V29 as a clear solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.56-7.50 (m, 2H), 7.20-7.11 (m, 2H), 7.08 (m, 1H), 4.95 (s, 1H), 4.75 (d, J=13.3 Hz, 1H), 4.41 (s, 1H), 3.83 (s, 3H), 3.73 (m, 1H), 3.67 (s, 3H), 3.51 (septet, J=5.9 Hz, 1H), 3.41 (dd, J=14.0, 8.1 Hz, 1H), 3.11 (m, 1H), 3.04-2.94 (m, 2H), 2.50 (ddd, J=14.1, 8.1, 2.0 Hz, 1H), 2.44 (d, J=14.7 Hz, 1H), 2.27 (d, J=14.6 Hz, 1H), 1.87 (sextet, J=7.5 Hz, 1H), 1.70-1.53 (m, 3H), 1.39 (m, 1H), 1.27 (m, 1H), 1.15 (d, J=5.9 Hz, 3H), 0.92 (d, J=5.9 Hz, 3H), 0.86 (t, J=7.5 Hz, 3H).sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 172.0, 169.6, 151.3, 135.4, 134.6, 127.6, 123.0, 120.3, 118.5, 111.9, 111.0, 86.7, 82.3, 71.8, 68.9, 58.0, 56.1, 53.4, 50.6, 46.5, 41.8, 34.1, 29.4, 23.4, 22.3 (2C), 21.2, 8.1. HRMS (ESI): calc. for C.sub.28H.sub.38N.sub.2O.sub.6Na [M+Na].sup.+: 521.2622, found: 521.2628. MP: 158-160° C.

(579) TABLE-US-00001 TABLE 1 Crystal data and structure refinement for chip2. Identification code chip2 Empirical formula C28H38N2O6 Formula weight 498.60 Temperature 100(2) K Wavelength 1.54178 Å Crystal system Monoclinic Space group P2.sub.1 Unit cell dimensions a = 8.4703(3) Å α = 90°. b = 17.3342(5) Å ß = 113.5528(11)°. c = 9.7261(3) Å γ = 90°. Volume 1309.08(7) Å.sup.3 Z 2 Density (calculated) 1.265 Mg/m.sup.3 Absorption coefficient 0.720 mm.sup.−1 F(000) 536 Crystal size 0.211 × 0.101 × 0.083 mm.sup.3 Theta range for data collection 4.960 to 67.953°. Index ranges −9 ≤ h ≤ 10, −18 ≤ k ≤ 19, −11 ≤ l ≤ 11 Reflections collected 11256 Independent reflections 4338 [R(int) = 0.0388] Completeness to theta = 67.679° 96.0% Absorption correction Analytical Max. and min. transmission 0.9654 and 0.9123 Refinement method Full-matrix least-squares on F.sup.2 Data/restraints/parameters 4338/1/345 Goodness-of-fit on F.sup.2 1.095 Final R indices [I > 2sigma(I)] R1 = 0.0328, wR2 = 0.0870 [4175] R indices (all data) R1 = 0.0352, wR2 = 0.0936 Absolute structure parameter 0.05(9) Largest diff. peak and hole 0.282 and −0.287 e .Math. Å.sup.−3

(580) ##STR00151##

(581) Yield: 14%; 21.7 mg of V30 as a white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.59 (d, J=13.3 Hz, 1H), 7.52 (d, J=7.1 Hz, 1H), 7.21-7.10 (m, 3H), 4.81 (d, J=13.3 Hz, 1H), 4.56 (s, 1H), 4.28 (s, 1H), 3.81 (s, 3H), 3.74-3.66 (m, 4H), 3.54 (dd, J=14.0, 7.0 Hz, 1H), 3.40-3.26 (m, 2H), 3.19 (dd, J=13.6 Hz, 1H), 2.99-2.77 (m, 3H), 2.30 (dd, J=14.1, 9.5 Hz, 1H), 1.91-1.80 (m, 3H), 1.74 (m, 1H), 1.65-1.50 (m, 2H), 1.49-1.40 (m, 2H), 1.37-1.18 (m, 3H), 0.89-0.81 (m, 6H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 175.1, 169.8, 151.0, 135.6, 134.3, 128.3, 123.0, 120.5, 118.5, 113.1, 112.3, 87.1, 83.2, 73.4, 67.8, 59.6, 56.7, 54.1, 50.8, 41.1, 40.8, 33.3, 32.2, 27.4, 22.1 (2C), 19.7, 14.0, 8.1. HRMS (ESI): for C.sub.29H.sub.41N.sub.2O.sub.6 [M+H].sup.+: 513.2959, found: 513.2968. MP: 128-130° C.

(582) ##STR00152##

(583) Yield: 34%; 50.2 mg of V31 as a clear residue. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.53 (m, 2H), 7.22-7.12 (m, 2H), 7.10 (dd, J=6.8, 1.4 Hz, 1H), 4.82-4.71 (m, 2H), 4.28 (s, 1H), 3.82 (s, 3H), 3.76-3.66 (m, 4H), 3.42 (ddd, J=14.4, 7.7 Hz, 1H), 3.36-3.22 (m, 2H), 3.13 (m, 1H), 3.05-2.92 (m, 2H), 2.50 (dd, J=14.4, 7.7 Hz, 1H), 2.46 (d, J=14.6 Hz, 1H), 2.28 (d, J=14.6 Hz, 1H), 1.88 (sextet, J=7.5 Hz, 1H), 1.75-1.54 (m, 4H), 1.50-1.35 (m, 2H), 1.33-1.23 (m, 3H), 0.87 (t, J=7.6 Hz, 3H), 0.82 (t, J=7.5 Hz, 3H). 13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 172.2, 169.7, 151.5, 135.5, 133.9, 127.6, 123.0, 120.4, 118.5, 112.5, 111.1, 86.7, 82.4, 74.6, 68.4, 57.9, 56.1, 53.5, 50.7, 46.1, 42.0, 33.9, 31.9, 29.4, 22.4 (2C), 19.6, 14.0, 8.1. HRMS (ESI): C.sub.29H.sub.40N.sub.2O.sub.6Na [M+Na].sup.+: 535.2779, found: 535.2762.

(584) ##STR00153##

(585) Yield: 19%; 31.5 mg of V3 as a white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.63 (d, J=13.4 Hz, 1H), 7.41 (d, J=7.7 Hz, 1H), 7.24-7.09 (m, 5H), 6.99 (dd, J=7.8 Hz, 1H), 6.81 (d, J=7.8 Hz, 2H), 5.15 (s, 1H), 4.75 (d, J=13.4 Hz, 1H), 4.66 (s, 1H), 3.91 (s, 3H), 3.80 (s, 3H), 3.65-3.48 (m, 2H), 3.01 (d, J=13.9 Hz, 1H), 2.73 (dd, J=12.7 Hz, 1H), 2.54-2.35 (m, 2H), 2.30 (dd, J=13.6, 10.2 Hz, 1H), 2.07-1.73 (m, 4H), 1.63-1.56 (m, 2H), 1.37 (dd, J=16.0, 8.3 Hz, 1H), 0.95 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CD.sub.3Cl at 50° C.) δ 175.0, 169.7, 158.4, 150.3, 135.5, 133.1, 129.4, 128.2, 123.2 (2C), 121.0, 120.5, 118.8, 113.6, 112.1, 88.1, 83.1, 77.7, 59.5, 56.7, 54.4, 50.8, 41.0, 40.8, 33.3, 27.6, 22.0 (2C), 8.1. HRMS (ESI): calc. for C.sub.31H.sub.36N.sub.2O.sub.6Na [M+Na].sup.+: 555.2466, found: 555.2464. MP: 98-100° C.

(586) ##STR00154##

(587) Yield: 28%; 45.7 mg of V34 as a pinkish-white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.56 (d, J=13.3 Hz, 1H), 7.44 (d, J=7.7 Hz, 1H), 7.23-7.09 (m, 5H), 6.96 (dd, J=7.4, 7.2 Hz, 1H), 6.82 (d, J=8.4 Hz, 2H), 5.15 (s, 1H), 4.71 (d, J=13.3 Hz, 1H), 4.42 (s, 1H), 3.80 (s, 3H), 3.76 (s, 3H), 3.63-3.46 (m, 2H), 2.87 (td, J=14.0, 2.0 Hz, 1H), 2.75 (d, J=14.8 Hz, 1H), 2.65-2.47 (m, 2H), 2.47-2.32 (m, 2H), 2.05 (sextet, J=7.6 Hz, 1H), 1.90-1.74 (m, 2H), 1.73-1.57 (m, 3H), 1.37 (m, 1H), 0.92 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CD.sub.3Cl at 50° C.) δ 173.4, 169.7, 158.3, 150.7, 135.8, 133.3, 129.5, 127.8, 123.3, 123.2, 120.5, 120.3, 118.8, 115.6, 112.8, 111.1, 87.9, 82.3, 77.9, 58.4, 56.4, 53.8, 50.8, 45.1, 42.3, 28.6, 22.2, 8.1. HRMS (ESI): calc. for C.sub.31H.sub.37N.sub.2O.sub.6 [M+H].sup.+: 532.2646, found: 533.2649. MP: 78-80° C.

(588) ##STR00155##

(589) General Procedure for the synthesis of V4 or V46, V20-V22, V32-V33 & V84: V (108.4 mg, 0.306 mmol) was added to a flame-dried round bottom flask and dissolved in methanol (30.6 mL). N-phenylpropiolamide (67.0 mg, 0.458 mmol) was added as one portion, the reaction was heated to 64° C. and proceeded for 19 hours. Upon completion, the reaction was concentrated in vacuo, and the crude product was purified via column chromatography using a gradient of 100% hexanes to 1:1 hexanes:ethyl acetate to afford V4 or V46 (59.3 mg, 36%) as a yellow solid.

(590) ##STR00156##

(591) Yield: 36%; 59.3 mg of V4 or V46 as a yellow solid. H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.69 (d, J=13.0 Hz, 1H), 7.58 (d, J=8.6, 2H), 7.53 (m, 1H), 7.29 (dd, J=8.3 Hz, 2H), 7.24-7.14 (m, 4H), 7.04 (dd, J=7.4 Hz, 1H), 4.90 (d, J=13.0 Hz, 1H), 4.64 (s, 1H), 4.25 (s, 1H), 3.82 (s, 3H), 3.67 (d, J=13.7 Hz, 1H), 3.51 (dd, J=13.9, 6.6 Hz, 1H), 3.27-3.15 (m, 4H), 2.96-2.83 (m, 2H), 2.76 (d, J=13.5 Hz, 1H), 2.29 (dd, J=14.2, 8.6 Hz, 1H), 1.92-1.69 (m, 4H), 1.62 (m, 1H), 1.51 (m, 1H), 1.28 (m, 1H), 0.86 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 174.9, 167.1, 149.4, 139.7, 135.6, 133.6, 129.1, 128.2, 123.3, 123.1, 120.5, 120.0, 118.5, 113.5, 112.3, 90.1, 83.2, 75.5, 59.3, 56.9, 56.3, 54.3, 41.0, 40.6, 33.2, 27.2, 22.4, 22.0, 8.1. HRMS (ESI): calc. for C.sub.31H.sub.38N.sub.3O.sub.5 [M+H].sup.+: 532.2086, found: 532.2781. MP: 207-209° C.

(592) ##STR00157##

(593) Yield: 36%; 56.0 mg of V20 as a yellow solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.69 (d, J=13.0 Hz, 1H), 7.59 (d, J=8.1 Hz, 2H), 7.52 (m, 1H), 7.30 (dd, J=2H), 7.25-7.10 (m, 4H), 7.04 (td, J=7.3, 1.1 Hz, 1H), 4.89 (d, J=13.0 Hz, 1H), 4.65 (s, 1H), 4.34 (s, 1H), 3.81 (s, 3H), 3.67 (d, J=13.6 Hz, 1H), 3.51 (dd, J=14.2, 6.4 Hz, 1H), 3.39 (sextet, J=7.5 Hz, 2H), 3.17 (dd, J=15.2, 13.7 Hz, 1H), 2.95-2.79 (m, 3H), 2.28 (dd, J=13.2, 9.0 Hz, 1H), 1.93-1.79 (m, 3H), 1.74 (m, 1H), 1.67-1.42 (m, 2H), 1.26 (m, 1H), 1.07 (t, J=7.1 Hz, 3H), 0.86 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 174.9, 167.1, 149.4, 139.7, 135.5, 134.3, 129.1, 128.2, 123.3, 122.9, 120.4, 120.0, 118.5, 112.9, 112.3, 90.1, 83.2, 73.4, 63.4, 59.2, 56.9, 54.1, 41.0, 40.8, 33.3, 27.2, 22.5, 21.9, 15.4, 8.1. HRMS (ESI): calc. for C.sub.32H.sub.39N.sub.3O.sub.5Na [M+Na].sup.+: 568.2782, found: 568.2789. MP: 220-222° C.

(594) ##STR00158##

(595) Yield: 5%; 8.5 mg of V32 as a yellow solid. .sup.1H NMR: (600 MHz, CDCl.sub.3 at 50° C.) δ 7.71 (d, J=13.0 Hz, 1H), 7.53 (d, J=7.6 Hz, 3H), 7.30 (dd, J=7.8 Hz, 2H), 7.23-7.11 (m, 3H), 7.05 (dd, J=7.4 Hz, 1H), 6.82 (s, 1H), 4.85 (d, J=13.0 Hz, 1H), 4.54 (s, 1H), 4.43 (s, 1H), 3.80 (s, 3H), 3.70 (d, J=14.7 Hz, 1H), 3.58-3.48 (m, 2H), 3.15 (dd, J=13.7 Hz, 1H), 2.99-2.78 (m, 3H), 2.31 (dd, J=14.1, 9.7 Hz, 1H), 1.92-1.72 (m, 4H), 1.66-1.56 (m, 3H), 1.15 (d, J=5.9 Hz, 3H), 0.90 (d, J=5.9 Hz, 3H), 0.85 (t, J=7.8 Hz, 4H). .sup.13C NMR: (150 MHz, CDCl.sub.3 at 50° C.) δ 175.1, 166.9, 149.3, 139.6, 135.6, 135.3, 129.1, 128.4, 123.5, 122.9, 120.5, 120.2, 118.5, 112.6, 112.4, 90.1, 83.3, 70.4, 67.6, 59.4, 56.8, 54.0, 41.0, 40.9, 33.1, 27.3, 23.7, 22.0, 21.5 (2C), 8.1. HRMS (ESI): calc. for C.sub.33H.sub.41N.sub.3O.sub.5Na [M+Na].sup.+: 582.2938, found: 582.2953. MP: 226-228° C.

(596) ##STR00159##

(597) Yield: 5%; 8.5 mg of V33 as a yellow solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.70 (d, J=12.8 Hz, 1H), 7.55-7.48 (m, 3H), 7.28 (dd, J=8.6 Hz, 2H), 7.21-7.11 (m, 3H), 7.04 (dd, J=7.4 Hz, 1H), 6.66 (s, 1H), 4.86 (s, 1H), 4.73 (d, J=12.8 Hz, 1H), 4.45 (s, 1H), 3.79 (s, 3H), 3.70 (d, J=13.9 Hz, 1H), 3.54 (m, 1H), 3.15 (dd, J=13.5 Hz, 1H), 2.97-2.79 (m, 3H), 2.31 (dd, J=13.8, 8.5 Hz, 1H), 1.91-1.72 (m, 4H), 1.66-1.44 (m, 3H), 1.28 (m, 1H), 1.16 (d, J=6.1 Hz, 3H), 0.92 (d, J=6.2 Hz, 3H), 0.86 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 172.3, 166.9, 149.8, 139.6, 135.6, 134.9, 129.1, 127.9, 123.4, 123.0, 120.3, 120.0, 118.6, 111.7, 111.2, 89.8, 82.3, 72.0, 69.1, 57.7, 55.7, 53.6, 46.6, 42.0, 33.7, 29.3, 23.5, 22.5, 21.4, 8.2. HRMS (ESI): calc. for C.sub.33H.sub.41N.sub.3O.sub.5Na [M+Na].sup.+: 582.2938, found: 582.2943. MP: 160-162° C.

(598) ##STR00160##

(599) Yield: 23%; 45.5 mg of V21 as a yellow solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.72 (d, J=13.1 Hz, 1H), 7.61 (d, J=8.2 Hz, 2H), 7.40 (dd, J=8.4, 7.6 Hz, 1H), 7.31 (dd, J=8.5, 7.4 Hz, 2H), 7.22-7.16 (m, 2H), 7.15-7.08 (m, 3H), 7.07-7.02 (m, 2H), 6.92 (td, J=7.3, 1.1 Hz, 1H), 6.84-6.80 (m, 2H), 5.14 (s, 1H), 4.76 (d, J=13.1 Hz, 1H), 4.70 (s, 1H), 3.88 (s, 3H), 3.58-3.42 (m, 2H), 2.97 (d, J=14.1 Hz, 1H), 2.72 (dt, J=14.0, 6.9 Hz, 1H), 2.48-2.38 (m, 2H), 2.24 (dd, J=14.0, 9.7 Hz, 1H), 2.04-1.76 (m, 5H), 1.55 (ddd, J=16.7, 9.0, 6.1 Hz, 1H), 1.35 (dd, J=15.7, 8.3 Hz, 1H), 0.91 (t, J=7.6 Hz, 3H). Note: .sup.1H spectrum referenced TMS at 0.00 ppm. .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.): δ 175.0, 166.9, 158.4, 148.1, 139.6, 135.2, 133.1, 129.3, 129.2, 128.0, 123.3, 123.0, 121.2, 120.4, 119.7, 118.7, 113.3, 112.1, 90.7, 82.9, 78.0, 60.1, 55.7, 54.5, 40.7, 40.5, 33.1, 27.4, 22.0, 20.6 (2C), 8.1. HRMS (ESI): calc. for C.sub.36H.sub.40N.sub.3O.sub.5 [M+H].sup.+: 594.2962, found: 594.2986. MP: 200-202° C.

(600) ##STR00161##

(601) Yield: 45%; 95.2 mg of V22 as a yellow solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.65 (d, J=12.8 Hz, 1H), 7.55-7.47 (m, 3H), 7.41 (s, 1H), 7.37 (d, J=9.0 Hz, 2H), 7.24-7.15 (m, 3H), 4.88 (d, J=12.8 Hz, 1H), 4.70 (s, 1H), 4.21 (s, 1H), 3.81 (s, 3H), 3.62 (d, J=14.2 Hz, 1H), 3.47 (dd, J=14.2, 7.2 Hz, 1H), 3.25-3.11 (m, 4H), 2.94-2.82 (m, 2H), 2.75 (d, J=14.0 Hz, 1H), 2.27 (dd, J=14.5, 8.7 Hz, 1H), 1.92-1.63 (m, 4H), 1.64-1.41 (m, 2H), 1.26 (dd, J=16.0, 7.6 Hz, 1H), 0.85 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) S 174.7, 167.1, 149.6, 138.9, 135.6, 133.4, 131.9, 128.2, 123.1, 121.3, 120.5, 118.5, 115.5, 113.4, 112.3, 89.8, 83.2, 75.4, 59.1, 56.7, 56.3, 54.2, 41.0, 40.6, 33.1, 27.2, 22.3, 22.0, 8.1. HRMS (ESI): calc. for C.sub.31H.sub.36BrN.sub.3O.sub.5 [M+Na].sup.+: 632.1731, found: 632.1759. MP: 201-203° C.

(602) ##STR00162##

(603) Yield: 11%; 8.8 mg of V84 as a yellow solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.68 (d, J=13.2 Hz, 1H), 7.53 (m, 1H), 7.46 (d, J=9.0 Hz, 2H), 7.41 (d, J=9.0 Hz, 2H), 7.24-7.12 (m, 3H), 6.78 (s, 1H), 4.80 (d, J=13.2 Hz, 1H), 4.54 (s, 1H), 4.32 (s, 1H), 3.81 (s, 3H), 3.70 (d, J=14.4 Hz, 1H), 3.55 (dd, J=14.6, 7.0 Hz, 1H), 3.38 (dd, J=15.0, 13.8 Hz, 2H), 3.19 (dd, J=13.5 Hz, 1H), 3.00-2.87 (m, 2H), 2.83 (d, J=14.0 Hz, 1H), 2.34 (dd, J=14.1, 8.7 Hz, 1H), 1.95-1.69 (m, 4H), 1.65-1.53 (m, 2H), 1.24 (m, 1H), 1.06 (t, J=6.9 Hz, 3H), 0.86 (t, J=7.3 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 175.0, 166.8, 149.8, 138.8, 135.6, 134.4, 132.1, 128.3, 123.1, 121.4, 120.6, 118.5, 115.7, 112.9, 112.4, 89.7, 83.2, 73.4, 63.5, 59.3, 57.0, 54.2, 41.1, 40.8, 33.2, 27.2, 22.0 (2C), 15.5, 8.1. HRMS (ESI): calc. for C.sub.32H.sub.38BrN.sub.3O.sub.5 [M+Na].sup.+: 646.1887, found: 646.1898. MP: 215-217° C.

(604) ##STR00163##

(605) Procedure for the synthesis of V76: V (139.9 mg, 0.395 mmol) was added to a flame-dried round-bottom flask and subsequently dissolved in a (2:1) chloroform:methanol solution (7.3 mL). A 3.0 M solution of cyanogen bromide in dichloromethane (0.39 mL, 1.18 mmol) was added dropwise and the reaction was stirred at room temperature for 4 hours. The reaction mixture was diluted with brine and extracted with dichloromethane. The organic layer was dried with sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified via column chromatography using a gradient of 100% chloroform to 24:1 chloroform:acetone to afford V76 (68.0 mg, 42%) as a white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.52 (d, J=7.3z Hz, 1H), 7.23-7.13 (m, 3H), 4.70 (s, 1H), 4.55 (s, 1H), 3.84 (s, 3H), 3.79 (dt, J=13.7, 2.9 Hz, 1H), 3.53 (dd, J=13.1, 6.4 Hz, 1H), 3.35 (s, 3H), 3.16 (ddd, J=15.3, 12.3, 3.1 Hz, 1H), 3.06 (dt, J=13.7, 2.9 Hz, 1H), 2.80 (d, J=13.8 Hz, 1H), 2.68 (ddd, J=15.3, 12.3, 3.1 Hz, 1H), 2.08 (dd, J=13.1, 6.4 Hz, 1H), 1.98-1.85 (m, 3H), 1.82-1.67 (m, 2H), 1.59 (m, 1H), 1.30 (dd, J=15.9, 8.2 Hz, 1H), 0.89 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 174.8, 135.3, 133.7, 127.9, 123.1, 120.6, 118.3, 118.0, 112.1, 112.0, 83.0, 75.5, 56.8, 56.4, 55.4, 54.5, 41.0, 40.6, 32.6, 26.8, 23.5, 21.4, 8.1. HRMS (ESI): calc. for C.sub.23H.sub.29N.sub.3O.sub.4Na [M+Na].sup.+: 434.2050, found: 434.2068. MP: 241-243° C.

(606) ##STR00164##

(607) Procedure for the synthesis of V12: V (2.01 g, 5.66 mmol) was added to a flame-dried round-bottom flask and dissolved in toluene (19.0 mL). p-Toluenesulfonic acid monohydrate (2.15 g, 11.32 mmol) was added to the solution and the round-bottom flask was equipped with a dean-stark trap. The reaction was heated to reflux for 2 hours, upon completion, the reaction was basified to pH ˜6-7 with 1 M NaOH and extracted with ethyl acetate. The crude extract was dried with sodium sulfate, filtered, concentrated in vacuo, and purified via column chromatography using a gradient of 100% hexanes to 1:1 hexanes:ethyl acetate with 1% triethylamine throughout to afford V12 (1.61 g, 84%) as a light yellow solid. Note: V12 is a known compound (CAS No. 4880-92-6). The spectral data below are consistent with literature..sup.4 1H NMR: (600 MHz, CDCl.sub.3) δ 7.47 (d, J=7.7 1H), 7.23 (d, J=8.3 Hz, 1H), 7.17 (td, J=7.1, 1.1 Hz, 1H), 7.13 (td, J=7.2, 0.9 Hz, 1H), 6.14 (s, 1H), 4.17 (s, 1H), 3.95 (s, 3H), 3.38 (dd, J=13.9, 6.2 Hz, 1H), 3.27 (td, J=11.7, 5.5 Hz, 1H), 3.03 (m 1H), 2.70-2.60 (m, 2H), 2.54 (dd, J=16.4, 3.4 Hz, 1H), 2.00-1.86 (m, 2H), 1.75 (m, 1H), 1.52 (d, J=13.7 Hz, 1H), 1.42 (dt, J=13.2, 2.9 Hz, 1H), 1.06-0.98 (m, 4H). .sup.13C NMR: (150 MHz, CDCl.sub.3) δ 164.0, 134.3, 130.9, 129.2, 128.4, 128.3, 122.2, 120.5, 118.5, 112.6, 108.9, 55.9, 52.7, 51.7, 45.1, 37.9, 28.7, 27.5, 20.4, 16.5, 8.9. MP: 159-161° C.

(608) ##STR00165##

(609) Procedure for the synthesis of V42: V12 (503.2 mg, 1.50 mmol) was added to a flame-dried microwave flask and dissolved in N,N-dimethylformamide (15.0 mL). A 3M solution of cyanogen bromide in dichloromethane (1.5 mL, 4.50 mmol) was added dropwise to the resulting solution. The reaction was subjected to microwave irradiation at 100° C. for six minutes. The reaction was cooled to room temperature, diluted with ethyl acetate, and quenched with brine (3×100 mL). The organic layer was dried with sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified via column chromatography using a gradient of 100% chloroform to 99:1 chloroform:acetone to yield V42 (310.2 mg, 47%) as an orange-white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.59 (d, J=7.6, 1H), 7.28-7.14 (m, 3H), 6.15 (d, J=1.5 Hz, 1H), 4.11 (d, J=1.5 Hz, 1H), 3.93 (s, 3H), 3.76 (td, J=9.5, 7.1 Hz, 1H), 3.63 (td, J=9.5, 7.1 Hz, 1H), 3.48-3.29 (m, 3H), 3.07 (td, J=12.1, 3.0 Hz, 1H), 2.01 (d, J=13.4 Hz, 1H), 1.79-1.56 (m, 2H), 1.30 (td, J=13.1, 3.9 Hz, 1H), 1.11-0.96 (m, 2H), 0.69 (t, J=7.5 Hz, 3H). Note: H spectrum referenced TMS at 0.00 ppm. .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 163.2, 134.6, 129.9, 128.0, 127.9, 127.6, 123.9, 121.2, 119.2, 117.5, 116.6, 112.7, 56.6, 52.8, 49.9, 39.4, 32.2, 31.5, 31.4, 28.6, 21.7, 8.1. HRMS (ESI): calc. for C.sub.22H.sub.24BrN.sub.3O.sub.2Na [M+Na].sup.+: 464.0944, found: 464.0959. MP: 115-117° C.

(610) ##STR00166##

(611) Procedure for the synthesis of V43: V42 (256.1 mg, 0.579 mmol) was added to a flame-dried microwave flask and dissolved in N,N-dimethylformamide (6.00 mL). Sodium azide (301.1 mg, 4.63 mmol) was added to the resulting solution and the reaction was subjected to microwave irradiation at 100° C. for six minutes. The reaction was cooled to room temperature, diluted with ethyl acetate, and quenched with brine (3×50 mL). The organic layer was dried with sodium sulfated, filtered, and concentrated in vacuo. The crude material was purified via column chromatography using a gradient of 100% chloroform to 99:1 chloroform:acetone to yield V43 (174.0 mg, 73%) as a white foam. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.58 (m, 1H), 7.26 (m, 1H), 7.23-7.15 (m, 2H), 6.15 (d, J=1.7 Hz, 1H), 4.11 (d, J=1.7 Hz, 1H), 3.96 (s, 3H), 3.72 (ddd, J=12.2, 8.2, 5.7 Hz, 1H), 3.61 (dt, J=12.2, 7.9 Hz, 1H), 3.48 (dp, J=10.3, 2.1 Hz, 1H), 3.21-3.03 (m, 3H), 2.13 (dt, J=13.8, 3.5 Hz, 1H), 1.89-1.70 (m, 2H), 1.42 (td, J=13.2, 4.2 Hz, 1H), 1.17-1.01 (m, 2H), 0.75 (t, J=7.5 Hz, 3H). Note: .sup.1H spectrum referenced TMS at 0.00 ppm. .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 163.4, 134.7, 130.1, 128.2, 128.1, 127.4, 124.0, 121.2, 119.3, 116.7, 116.6, 112.7, 56.8, 52.8, 51.5, 50.1, 39.4, 32.3, 31.4, 24.4, 21.8, 8.1. HRMS (ESI): calc. for C.sub.22H.sub.24N.sub.6O.sub.2Na [M+Na].sup.+: 427.1853, found: 427.1860. MP: 41-43° C.

(612) ##STR00167##

(613) Procedure for the synthesis of V44: V43 (157.0 mg, 0.388 mmol) was added to a flame-dried round-bottom flask and dissolved in methanol (6.50 mL). Triphenylphosphine (152.7 mg, 0.582 mmol) was added to the resulting solution, and the reaction was heated to reflux. The reaction proceeded for 1 hour, then cooled to room temperature and concentrated in vacuo. The crude material was purified via column chromatography using a gradient of 100% ethyl acetate to 90:10 ethyl acetate:methanol with 1% triethylamine throughout to yield V44 (121.7 mg, 83%) as a clear residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.59 (d, J=7.8 Hz, 1H), 7.23-7.09 (m, 3H), 6.12 (d, J=1.7 Hz, 1H), 4.13 (d, J=1.7 Hz, 1H), 3.92 (s, 3H), 3.38 (d, J=12.2 Hz, 1H), 3.17-2.86 (m, 5H), 2.18 (s, 2H), 2.03 (d, J=13.2 Hz, 1H), 1.81-1.61 (m, 2H), 1.35 (td, J=14.0, 4.2 Hz, 1H), 0.99 (q, J=7.5 Hz, 2H), 0.71-0.63 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 163.5, 134.8, 130.2, 128.7, 127.8, 127.2, 123.8, 121.0, 119.7, 118.2, 116.7, 112.5, 56.6, 52.7, 49.9, 42.4, 39.5, 32.3, 31.4, 28.1, 21.8, 8.0. HRMS (ESI): calc. for C.sub.22H.sub.26N.sub.4O.sub.2Na [M+Na].sup.+: 401.1948, found: 401.1962.

(614) ##STR00168##

(615) General Procedure for the synthesis of V45, V80-V81: V44 (31.5 mg, 0.083 mmol) was added to a flame-dried round-bottom flask and dissolved in dichloromethane (1.2 mL). The reaction was cooled to 0° C. in an ice-water bath, then triethylamine (23.0 μL, 0.166 mmol) was added dropwise. Acetyl chloride (5.0 μL, 0.091 mmol) and catalytic dimethylaminopyridine in dichloromethane were added dropwise to the reaction. The reaction slowly warmed to room temperature and proceeded for 5 hours, then was quenched with saturated aqueous sodium bicarbonate, extracted with dichloromethane, washed with brine, and crude extract was dried with sodium sulfate. The organic layer was filtered, concentrated in vacuo, and purified via column chromatography using a gradient of 100% hexanes to 49:1 ethyl acetate:methanol to yield V45 (22.7 mg, 65%) as a clear residue.

(616) ##STR00169##

(617) Yield: 65%; 22.7 mg of V45 as a clear residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.64-7.57 (d, J=7.8 Hz, 1H), 7.30-7.14 (m, 3H), 6.21-6.10 (m, 2H), 4.08 (d, J=1.7 Hz, 1H), 3.98 (s, 3H), 3.72 (ddd, J=13.7, 6.7, 5.3 Hz, 1H), 3.60 (ddd, J=13.7, 6.4, 5.3 Hz, 1H), 3.49 (dt, J=12.3, 1.8 Hz, 1H), 3.26-3.14 (m, 2H), 2.86 (ddd, J=14.4, 7.5, 5.3 Hz, 1H), 2.12 (d, J=11.4 Hz, 1H), 1.92 (s, 3H), 1.89-1.70 (m, 3H), 1.46 (td, J=13.5, 4.3 Hz, 1H), 1.03 (sextet, J=7.5 Hz, 2H), 0.73 (t, J=7.5 Hz, 3H). Note: 1H spectrum referenced TMS at 0.00 ppm. .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 170.9, 163.5, 134.9, 130.3, 128.8, 127.7, 127.4, 124.1, 121.3, 119.6, 118.0, 117.1, 112.7, 56.4, 52.9, 49.7, 40.1, 39.7, 32.3, 31.4, 24.4, 23.5, 21.9, 8.0. HRMS (ESI): calc. for C.sub.24H.sub.28N.sub.4O.sub.3Na [M+Na].sup.+: 443.2054, found: 443.2090.

(618) ##STR00170##

(619) Yield: 34%; 13.4 mg of V80 as a clear residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.65 (d, J=7.8, 1H), 7.39 (m, 1H), 7.26-7.13 (m, 3H), 7.10 (dt, J=3.4, 0.8 Hz, 1H), 6.78 (t, J=6.3 Hz, 1H), 6.46 (ddd, J=3.5, 1.8, 0.7 Hz, 1H), 6.14 (d, J=1.7 Hz, 1H), 4.06 (d, J=1.7 Hz, 1H), 3.97 (s, 3H), 3.84 (dq, J=13.4, 6.7 Hz, 1H), 3.73 (dq, J=13.0, 6.7 Hz, 1H), 3.36-3.23 (m, 2H), 3.12-2.98 (m, 2H), 2.11 (dt, J=13.9, 3.1 Hz, 1H), 1.86-1.70 (m, 2H), 1.40 (td, J=13.4, 3.9 Hz, 1H), 1.12-0.91 (m, 2H), 0.70 (t, J=7.5 Hz, 3H). Note: .sup.1H spectrum referenced TMS at 0.00 ppm. .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 163.5, 159.0, 148.2, 144.2, 134.9, 130.4, 128.6, 127.9, 127.2, 124.0, 121.2, 119.6, 117.7, 116.7, 114.1, 112.7, 112.1, 56.6, 52.8, 49.7, 40.2, 39.5, 32.4, 31.5, 24.7, 21.9, 8.1. HRMS (ESI): calc. for C.sub.27H.sub.28N.sub.4O.sub.4Na [M+Na].sup.+: 495.2003, found: 495.2021.

(620) ##STR00171##

(621) Yield: 75%; 33.8 mg of V81 as a white foam. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.63-7.57 (m, 3H), 7.49 (d, J=8.6 Hz, 2H), 7.24-7.17 (m, 2H), 7.13 (td, J=7.3, 1.4 Hz, 1H), 6.84 (t, J=6.2 Hz, 1H), 6.13 (d, J=1.7 Hz, 1H), 4.04 (d, J=1.7 Hz, 1H), 3.97 (s, 3H), 3.90-3.75 (m, 2H), 3.35 (ddd, J=14.6, 7.5, 5.7 Hz, 1H), 3.18 (dt, J=12.7, 2.1 Hz, 1H), 3.03-2.88 (m, 2H), 2.09 (d, J=14.1 Hz, 1H), 1.87-1.62 (m, 2H), 1.40 (td, J=14.1, 4.0 Hz, 1H), 1.11-0.93 (m, 2H), 0.71 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 167.0, 163.4, 134.8, 133.2, 131.7, 130.3, 129.1, 128.9, 127.6, 127.2, 126.2, 124.1, 121.3, 119.6, 118.0, 117.0, 112.7, 56.5, 52.9, 49.4, 41.1, 39.6, 32.3, 31.4, 24.2, 21.9, 8.0. HRMS (ESI): calc. for C.sub.29H.sub.29BrN.sub.4O.sub.3Na [M+Na].sup.+: 583.1315, found: 583.1299. MP: 83-85° C.

(622) ##STR00172##

(623) Procedure for the synthesis of V85: V43 (19.7 mg, 0.049 mmol) was added to a flame-dried round-bottom flask and dissolved in toluene (0.250 mL). Water (4.0 μL, 0.245 mmol) and trifluoroacetic acid (11.0 μL, 0.097 mmol) were added sequentially to the resultant solution. The reaction was heated to 80° C. and proceeded for 8 hours. The reaction was quenched with 1 M aqueous sodium carbonate, extracted with ethyl acetate, washed with brine, and dried with sodium sulfate. The crude extract was filtered, concentrated in vacuo, and purified via column chromatography using a gradient of 100% hexanes, 3:1 hexanes:ethyl acetate, and 100% ethyl acetate with 1% triethylamine throughout to yield V85 (17.9 mg, 97%) as a clear residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.52 (dt, J=7.5, 1.2 Hz, 1H), 7.23-7.12 (m, 3H), 6.26 (d, J=1.8 Hz, 1H), 3.95 (s, 3H), 3.70 (d, J=1.8 Hz, 1H), 3.61-3.55 (m, 2H), 3.15-2.91 (m, 3H), 2.70 (td, J=12.2, 3.1 Hz, 1H), 2.09 (dt, J=13.6, 3.7 Hz, 1H), 2.01 (s, 1H), 1.73-1.54 (m, 2H), 1.43 (td, J=13.8, 4.1 Hz, 1H), 1.25 (m, 1H), 1.11-0.99 (m, 2H), 0.74 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) 164.0, 135.0, 134.3, 130.8, 129.0, 128.5, 122.8, 120.7, 118.4, 112.5, 111.7, 55.8, 52.7, 52.0, 45.9, 39.4, 33.7, 31.8, 24.1, 23.9, 8.1. HRMS (ESI): calc. for C.sub.21H.sub.26N.sub.5O.sub.2 [M+H].sup.+: 380.2081, found: 380.2095.

(624) ##STR00173##

(625) Procedure for the synthesis of V82: AV # (31.7 mg, 0.084 mmol) was added to a flame-dried round-bottom flask and dissolved in dichloromethane (1.7 mL). The reaction was cooled to 0° C. in an ice-water bath, then triethylamine (23.4 μL, 0.168 mmol) was added dropwise. 4-chlorobenzoyl chloride (11.0 μL, 0.088 mmol) and catalytic dimethylaminopyridine in dichloromethane was added dropwise to the reaction. The reaction slowly warmed to room temperature and proceeded for 3 hours, then quenched with saturated aqueous sodium bicarbonate, extracted with dichloromethane, washed with brine, and crude extract was dried with sodium sulfate. The organic layer was filtered, concentrated in vacuo, and purified via column chromatography using a gradient of 100% hexanes to 5:1 hexanes:ethyl acetate to yield V82 (30.6 mg, 70%) as a white-yellow residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.56 (dd, J=6.5, 1.7 Hz, 1H), 7.50 (d, J=8.7 Hz, 2H), 7.46 (d, J=8.7 Hz, 2H), 7.24-7.14 (m, 2H), 7.04 (dd, J=6.5, 1.7 Hz, 1H), 6.20 (s, 1H), 6.02 (s, 1H), 3.94 (s, 3H), 3.81 (m, 1H), 3.66-3.48 (m, 2H), 3.19-3.06 (m, 2H), 2.87 (m, 1H), 1.84-1.57 (m, 4H), 1.50 (td, J=13.2, 4.0 Hz, 1H), 1.39 (d, J=13.7 Hz, 1H), 1.03 (t, J=7.4 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 170.9, 163.9, 136.4, 134.3, 133.9, 129.5, 129.3, 129.2, 128.7, 128.4, 126.5, 123.0, 121.1, 118.4, 112.2, 112.0, 53.4, 52.8, 51.6, 43.0, 39.5, 28.7, 27.1, 24.3, 20.9, 8.8. HRMS (ESI): calc. for C.sub.28H.sub.28ClN.sub.5O.sub.3Na [M+Na].sup.+: 540.1773, found: 540.1765.

(626) ##STR00174##

(627) General Procedure for the synthesis of V60-V65: V12 (157.7 mg, 0.469 mmol) was added to a flame-dried round-bottom flask and dissolved in a 2:1 tetrahydrofuran:water solution (30.0 mL). Methyl propiolate (62.5 μL, 0.703 mmol) was added dropwise and the reaction was stirred at room temperature. The reaction was heated to 66° C. for 4 hours, then the reaction was cooled to room temperature, washed with saturated aqueous brine, and extracted with ethyl acetate. The organic layer was dried with sodium sulfate, filtered, concentrated in vacuo, and the crude product was purified via column chromatography using a gradient of 100% hexanes to 3:2 hexanes:ethyl acetate to afford V60 (154.0 mg, 75%) as a white foam.

(628) ##STR00175##

(629) Yield: 75%; 154.0 mg of V60 as a white foam. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.48-7.41 (m, 2H), 7.24 (d, J=7.6 Hz, 1H), 7.20 (td, J=7.0, 1.2 Hz, 1H), 7.15 (td, J=7.0, 1.2 Hz, 1H), 6.16 (s, 1H), 4.69 (d, J=13.3 Hz, 1H), 4.53 (s, 1H), 3.92 (s, 3H), 3.72-3.60 (m, 4H), 3.25-3.08 (m, 2H), 2.93-2.77 (m, 2H), 2.41 (ddd, J=14.9, 6.4, 3.3 Hz, 1H), 2.32 (s, 1H), 1.83-1.65 (m, 2H), 1.58 (ddd, J=15.5, 7.2, 3.2, Hz 1H), 1.32 (m, 1H), 0.97 (t, J=7.2 Hz, 3H), 0.86 (m, 1H), 0.59 (m, 1H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 169.7, 164.2, 152.1, 136.1, 135.8, 129.7, 129.0, 128.2, 123.7, 121.1, 118.7, 114.4, 112.9, 86.6, 65.7, 58.6, 55.8, 52.6, 50.7, 44.1, 31.3, 26.7, 21.7 (2C), 8.0. Note: Presence of two overlapping carbon signals confirmed by HSQC, see NMR spectra. HRMS (ESI): calc. for C.sub.25H.sub.31N.sub.2O.sub.5 [M+H].sup.+: 439.2227, found: 439.2230. MP: 93-95° C.

(630) ##STR00176##

(631) Yield: 91%; 70.3 mg of V61 as a white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.57-7.48 (m, 2H), 7.29 (d, J=8.1 Hz, 1H), 7.23 (dd, J=7.0, 1.1 Hz, 1H), 7.18 (dd, J=7.0, 1.1 Hz, 1H), 6.22 (s, 1H), 4.78 (d, J=13.3 Hz, 1H), 4.09 (s, 1H), 3.93 (s, 3H), 3.76 (dt, J=13.7, 3.1 Hz, 1H), 3.70 (s, 3H), 3.31 (dd, J=14.5, 9.6 Hz, 1H), 3.26-3.18 (m, 4H), 3.01-2.91 (m, 2H), 2.47 (ddd, J=14.4, 6.9, 2.7 Hz, 1H), 1.88-1.59 (m, 3H), 1.40 (m, 1H), 0.97 (t, J=7.4 Hz, 3H), 0.93-0.61 (m, 2H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 169.6, 164.1, 151.8, 135.9, 133.3, 129.8, 129.5, 128.0, 123.7, 121.0, 118.4, 116.5, 113.0, 86.7, 74.9, 59.1, 56.1 (2C), 52.5, 50.7, 43.7, 31.7, 26.8, 21.9 (2C), 8.0. HRMS (ESI): calc. for C.sub.26H.sub.33N.sub.2O.sub.5 [M+H].sup.+: 453.2384, found: 453.2381. MP: 76-78° C.

(632) ##STR00177##

(633) Yield: 87%; 130.0 mg of V62 as a white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.55 (d, J=13.3 Hz, 1H), 7.48 (d, J=7.6 Hz, 1H), 7.27 (m, 1H), 7.21 (td, J=6.9, 1.2 Hz, 1H), 7.16 (td, J=6.9, 1.2 Hz, 1H), 6.23 (d, J=1.5 Hz, 1H), 4.78 (d, J=13.3 Hz, 1H), 4.30 (d, J=1.5 Hz, 1H), 3.93 (s, 3H), 3.75 (dt, J=13.6, 3.3 Hz, 1H), 3.69 (s, 3H), 3.58 (septet, J=7.0 Hz, 1H), 3.31 (dd, J=14.3, 8.5 Hz, 1H), 3.189 (m, 1H), 3.01-2.91 (m, 2H), 2.45 (ddd, J=14.3, 8.5, 2.3 Hz, 1H), 1.82 (sextet, J=7.4 Hz, 1H), 1.74-1.57 (m, 2H), 1.45 (m, 1H), 1.13 (d, J=7.0 Hz, 3H), 0.97 (t, J=7.4 Hz, 3H), 0.90 (d, J=7.0 Hz, 3H), 0.87-0.80 (m, 2H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 169.5, 164.2, 151.5, 135.8, 135.0, 130.3, 129.4, 128.0, 123.5, 120.9, 118.3, 115.3, 112.8, 86.7, 70.5, 68.4, 59.1, 56.0, 52.4, 50.6, 44.0, 31.4, 26.5, 23.6, 21.7 (2C), 21.3, 8.0. HRMS (ESI): calc. for C.sub.28H.sub.37N.sub.2O.sub.5 [M+H].sup.+: 481.2697, found: 481.2685. MP: 72-74° C.

(634) ##STR00178##

(635) Yield: 15%; 19.9 mg of V63 as a white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.59 (d, J=13.4 Hz, 1H), 7.41 (dd, J=7.8, 1.3 Hz, 1H), 7.29 (m, 1H), 7.23 (td, J=6.9, 1.2 Hz, 1H), 7.20-7.12 (m, 3H), 6.96 (m, 1H), 6.88-6.83 (m, 2H), 6.35 (d, J=1.5 Hz, 1H), 5.04 (d, J=1.5 Hz, 1H), 4.78 (d, J=13.4 Hz, 1H), 4.00 (s, 3H), 3.77 (s, 3H), 3.67 (dt, J=13.6, 3.0 Hz, 1H), 3.39 (dd, J=14.4, 8.3 Hz, 1H), 2.87 (t, J=12.6 Hz, 1H), 2.77 (t, J=13.1 Hz, 1H), 2.65 (d, J=14.4 Hz, 1H), 2.48 (ddd, J=14.1, 7.8, 2.4 Hz, 1H), 2.00 (sextet, J=7.5 Hz, 1H), 1.88 (sextet, J=7.5 Hz, 1H), 1.78 (ddd, J=14.1, 7.8, 2.4 Hz, 1H), 1.56 (m, 1H), 1.06 (t, J=7.5 Hz, 3H), 0.99-0.89 (m, 2H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 169.6, 164.2, 158.1, 151.3, 135.8, 133.3, 129.8, 129.5, 129.3, 128.0, 123.8, 123.0, 121.0, 119.9, 118.7, 116.0, 112.9, 87.5, 76.0, 59.2, 56.1, 52.6, 50.8, 43.9, 31.8, 26.7, 21.8 (2C), 8.2. HRMS (ESI): calc. for C.sub.31H.sub.34N.sub.2O.sub.5Na [M+Na].sup.+: 537.2360, found: 537.2365. MP: 108-111° C.

(636) ##STR00179##

(637) Yield: 15%; 19.9 mg of V64 as a white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.67 (d, J=13.4 Hz, 1H), 7.38 (d, J=7.3 Hz, 1H), 7.25-7.16 (m, 2H), 7.13 (dd, J=7.2 Hz, 1H), 7.02-6.96 (m, 2H), 6.75 (dd, J=7.9, 0.7 Hz, 1H), 6.72 (dd, J=7.7 Hz, 1H), 6.29 (s, 1H), 6.25 (s, 1H), 5.11 (s, 1H), 4.76 (d, J=13.4 Hz, 1H), 4.02 (s, 3H), 3.84-3.65 (m, 4H), 3.61 (dd, J=14.0, 7.5 Hz, 1H), 3.19 (dd, J=14.9, 13.3 Hz, 1H), 2.98 (dd, J=14.1, 13.3 Hz, 1H), 2.67 (d, J=14.7 Hz, 1H), 2.58 (dd, J=14.3, 8.4 Hz, 1H), 1.93-1.66 (m, 3H), 1.40 (m, 1H), 1.10 (sextet, J=7.7 Hz, 1H), 0.94 (m, 1H), 0.82 (t, J=7.7 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 170.7, 164.7, 154.0, 152.2, 138.2, 135.3, 130.6, 130.0, 129.9, 128.8, 127.7, 126.3, 122.6, 121.0 (2C), 118.1, 115.6, 113.4, 112.2, 87.2, 59.3, 57.3, 52.7, 51.0, 44.1, 36.7, 34.7, 24.6, 21.7 (2C), 8.2. HRMS (ESI): calc. for C.sub.31H.sub.35N.sub.2O.sub.5 [M+H].sup.+: 515.2540, found: 515.2549. MP: 240-242° C., decomposed.

(638) ##STR00180##

(639) Yield: 35%; 46.5 mg of V65 as a brown-white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.66 (d, J=13.3 Hz, 1H), 7.36 (d, J=7.6 Hz, 1H), 7.25-7.16 (m, 2H), 7.13 (m, 1H), 6.92 (d, J=8.2 Hz, 2H), 6.68 (d, J=8.2 Hz, 2H), 6.41 (s, 1H), 6.16 (s, 1H), 4.83 (d, J=13.3 Hz, 1H), 4.09 (s, 1H), 4.00 (s, 3H), 3.77 (s, 3H), 3.72 (m, 1H), 3.50 (dd, J=14.3, 7.5 Hz, 1H), 3.05-2.95 (m, 2H), 2.63 (dd, J=14.0, 4.0 Hz, 1H), 2.51 (dd, J=14.3, 8.2 Hz, 1H), 1.77-1.72 (m, 2H), 1.64 (m, 1H), 1.29 (m, 1H), 1.03-0.90 (m, 2H), 0.78 (t, J=7.3 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.): δ 170.6, 164.6, 155.5, 151.8, 138.0, 135.1, 130.5, 130.3, 130.2, 129.6, 128.7, 122.6, 121.1, 118.0, 115.5, 112.8, 112.2, 86.8, 52.8, 59.1, 56.4, 51.1, 45.6, 43.2, 34.4, 27.2, 21.8 (2C), 8.2. HRMS (ESI): calc. for C.sub.31H.sub.35N.sub.2O.sub.5 [M+H].sup.+: 515.2540, found: 515.2547. MP: 157-159° C.

(640) ##STR00181##

(641) Procedure for the synthesis of V50: Lithium aluminum hydride (2.69 g, 70.8 mmol) was added to a round-bottom flask containing tetrahydrofuran (142 mL) at 0° C. V (5.02 g, 14.2 mmol) was added portion-wise at 0° C. then warmed to room temperature. The reaction was heated to 66° C. and allowed to react for ˜1.5 hours, upon completion, the reaction was quenched with 1 M NaOH (˜2 mL) and distilled water (˜10 mL). This crude mixture was filtered through a frit funnel containing celite, and the filtrate was rinsed with warm ethyl acetate. Crude product was dried with sodium sulfate and concentrated in vacuo to afford V50 (4.17 g, 99%) as a yellow-white foam. Note: V50 is a known compound (CAS No. 3382-95-4). .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.63 (m, 1H), 7.48 (m, 1H), 7.17-7.09 (m, 2H), 4.10 (d, J=11.4 Hz, 1H), 3.87 (d, J=11.4 Hz, 1H), 3.71 (s, 1H), 3.19 (m, 2H), 2.94 (m, 1H), 2.55-2.47 (m, 2H), 2.33 (td, J=12.3, 3.0 Hz, 1H), 2.26-2.13 (m, 2H), 2.04 (d, J=15.1 Hz, 1H), 1.69 (qt, J=13.7, 4.7 Hz, 1H), 1.49 (m, 1H), 1.43-1.22 (m, 5H), 0.91 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 134.0, 132.4, 129.3, 121.3, 120.1, 118.5, 112.7, 105.7, 84.8, 67.6, 59.5, 50.8, 44.3, 44.2, 34.5, 28.9, 25.9, 20.8, 16.9, 7.8. MP: 180-182° C., lit. 180-182° C..sup.5

(642) ##STR00182##

(643) Procedure for the synthesis of V6: V50 (4.17 g, 12.8 mmol) was added to a round-bottom flask and dissolved in 3:1 solution of tetrahydrofuran:water (128 mL). Sodium periodate (13.7 g, 64.0 mmol) was added portion-wise and the reaction stirred at room temperature for 4 hours. The reaction was quenched with saturated aqueous sodium thiosulfate, extracted with ethyl acetate, and extract was dried with sodium sulfate. The crude extract was concentrated in vacuo to yield V6 (3.69 g, 93%) as a brownish-white solid. Note: V6 is a known compound (CAS No. 4880-88-0). .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 8.30 (dd, J=7.1, 1.8 Hz, 1H), 7.30 (dd, J=7.6, 1.8 Hz, 1H), 7.23-7.16 (m, 2H), 3.57 (s, 1H), 3.14 (dd, J=13.8, 6.3 Hz, 1H), 2.94 (ddd, J=13.0, 6.2 Hz, 1H), 2.72 (m, 1H), 2.50-2.37 (m, 3H), 2.28-2.13 (m, 2H), 1.89 (sextet, J=7.5 Hz, 1H), 1.60 (qt, J=12.9, 4.0 Hz, 1H), 1.48 (sextet, J=7.5 Hz, 1H), 1.32 (d, J=13.7 Hz, 1H), 1.22 (d, J=13.7 Hz, 1H), 0.83 (t, J=7.5 Hz, 4H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 167.4, 134.0, 132.0, 130.0, 124.0, 123.7, 117.9, 116.0, 112.1, 57.1, 50.3, 44.1, 43.9, 38.0, 28.1, 26.7, 20.5, 16.3, 7.6. MP: 168-170° C., lit. 168-170° C..sup.6

(644) ##STR00183##

(645) General Procedure for the synthesis of V66-V67: V6 (56.1 mg, 0.191 mmol) was added to a flame-dried round-bottom flask and dissolved in a 2:1 tetrahydrofuran:water solution (30.0 mL). Methyl propiolate (25.4 μL, 0.286 mmol) was added dropwise and the reaction was stirred at room temperature. The reaction was heated to 66° C. for 24 hours, then the reaction was washed with saturated aqueous brine, and extracted with ethyl acetate. The organic layer was dried with sodium sulfate, filtered, concentrated in vacuo, and the crude product was purified via column chromatography using a gradient of 100% hexanes to 3:2 hexanes:ethyl acetate to afford V66 (55.0 mg, 72%) as a white solid.

(646) ##STR00184##

(647) Yield: 72%; 55.0 mg of V66 as a white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 8.41 (d, J=8.1 Hz, 1H), 7.47 (d, J=13.4 Hz, 1H), 7.44 (d, J=8.1 Hz, 1H), 7.35 (td, J=7.3, 1.3 Hz, 1H), 7.29 (td, J=7.5, 1.3 Hz, 1H), 4.73-4.70 (m, 2H), 3.69-3.61 (m, 4H), 3.47 (dd, J=14.3, 7.4 Hz, 1H), 3.13-3.01 (m, 2H), 2.93-2.80 (m, 2H), 2.73 (s, 1H), 2.37 (d, J=17.4 Hz, 1H), 2.28 (dd, J=14.0, 8.7 Hz, 1H), 1.89 (sextet, J=7.5 Hz, 1H), 1.84-1.66 (m, 2H), 1.64-1.49 (m, 2H), 0.87 (t, J=7.5 Hz, 3H), 0.79 (dd, J=14.0, 8.7 Hz, 1H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) S 169.7, 169.3, 150.6, 136.7, 135.2, 129.1, 125.9, 124.2, 118.3, 117.1, 117.0, 87.8, 66.1, 58.6, 56.0 50.8, 43.6, 40.0, 33.8, 26.4, 22.3, 21.7, 7.9. HRMS (ESI): calc. for C.sub.23H.sub.28N.sub.2O.sub.4Na [M+Na].sup.+: 419.1941, found: 419.1945. MP: 86-88° C. solid.

(648) ##STR00185##

(649) Yield: 83%; 45.0 mg of V67 as a white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 8.46 (d, J=7.4 Hz, 1H), 7.55 (d, J=13.3 Hz, 1H), 7.48 (dd, J=7.4, 0.7 Hz, 1H), 7.39 (td, J=7.4, 0.7 Hz, 1H), 7.32 (td, J=7.4, 0.7 Hz, 1H), 4.80 (d, J=13.4 Hz, 1H), 4.14 (s, 1H), 3.77-3.66 (m, 4H), 3.55 (dd, J=14.2, 6.8 Hz, 1H), 3.21 (s, 3H), 3.14 (td, J=14.1, 2.6 Hz, 1H), 3.01 (d, J=17.3 Hz, 1H), 2.93 (m, 1H), 2.40-2.30 (m, 2H), 1.94 (sextet, J=7.6 Hz, 1H), 1.88-1.69 (m, 3H), 1.62-1.52 (m, 2H), 0.92-0.79 (m, 4H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) S 169.6, 169.4, 150.4, 135.5, 133.7, 128.9, 126.0, 124.1, 118.9, 118.2, 117.2, 87.9, 75.5, 58.9, 56.5, 55.8, 50.9, 43.6, 40.9, 34.1, 26.6, 22.4, 22.0, 7.9 HRMS (ESI): calc. for C.sub.24H.sub.31N.sub.2O.sub.4 [M+H].sup.+: 411.2278, found: 411.2269. MP: 116-118° C.

(650) TABLE-US-00002 TABLE 2 Crystal data and structure refinement for chip3. Identification code chip3 Empirical formula C25H31Cl3N2O4 Formula weight 529.87 Temperature 100(2) K Wavelength 1.54178 Å Crystal system Monoclinic Space group P2.sub.1 Unit cell dimensions a = 9.1112(2) Å α = 90°. b = 11.8304(3) Å ß = 95.6953(16)°. c = 11.7934(3) Å γ = 90°. Volume 1264.93(5) Å.sup.3 Z 2 Density (calculated) 1.391 Mg/m.sup.3 Absorption coefficient 3.565 mm.sup.−1 F(000) 556 Crystal size 0.135 × 0.042 × 0.021 mm.sup.3 Theta range for data collection 3.767 to 60.433°. Index ranges −8 ≤ h ≤ 10, −13 ≤ k ≤ 13, −13 ≤ l ≤ 13 Reflections collected 17062 Independent reflections 3665 [R(int) = 0.0762] Completeness to theta = 60.000° 98.5% Absorption correction Analytical Max. and min. transmission 0.9418 and 0.7793 Refinement method Full-matrix least-squares on F.sup.2 Data/restraints/parameters 3665/1/307 Goodness-of-fit on F.sup.2 0.979 Final R indices [I > 2sigma(I)] R1 = 0.0325, wR2 = 0.0721 [3241] R indices (all data) R1 = 0.0381, wR2 = 0.0738 Absolute structure parameter −0.001(11) Largest diff. peak and hole 0.234 and −0.226 e .Math. Å.sup.−3

(651) ##STR00186##

(652) Procedure for the synthesis of V6: V6 (89.0 mg, 0.302 mmol) was added to a flame-dried round-bottom flask and dissolved in a (2:1) chloroform:methanol solution (6.6 mL). A 3.0 M solution of cyanogen bromide in dichloromethane (0.30 mL, 0.906 mmol) was added dropwise to the reaction mixture and the reaction was stirred at room temperature for 21 hours. The reaction mixture was diluted with brine and extracted with dichloromethane. The organic layer was dried with sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified via column chromatography using a gradient of 100% hexanes, 3:1 hexanes:ethyl acetate, and 100% ethyl acetate to afford V77 (54.5 mg, 51%) as a brown residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 8.46 (dt, J=8.1 Hz, 1H), 7.47 (d, J=7.5 Hz, 1H), 7.39 (td, J=8.1, 1.2 Hz, 1H), 7.32 (td, J=7.5, 1.2 Hz, 1H), 4.45 (d, J=1.3 Hz, 1H), 3.77 (dt, J=13.9, 3.0 Hz, 1H), 3.45 (ddd, J=13.1, 7.4, 1.7 Hz, 1H), 3.29 (s, 3H), 3.09-3.02 (m, 3H), 2.82 (m, 1H), 2.40 (dd, J=17.4, 1.3 Hz, 1H), 2.24 (dd, J=13.1, 8.6 Hz, 1H), 2.10 (sextet, J=7.6 Hz, 1H), 1.86-1.58 (m, 4H), 0.94-0.86 (m, 4H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 169.4, 135.2, 133.9, 128.6, 126.0, 124.1, 118.0, 117.4, 117.2, 117.1, 75.5, 56.5, 55.2, 54.0, 43.5, 41.0, 32.8, 26.2, 23.1, 21.5, 7.9. HRMS (ESI): calc. for C.sub.21H.sub.26N.sub.3O.sub.2 [M+H].sup.+: 352.2020, found: 352.2025.

(653) ##STR00187##

(654) Procedure for the synthesis of V74: V67 (639.6 mg, 1.56 mmol) was added to a flame-dried round-bottom flask containing a stirring 1.0 M (HCl:MeOH) solution (15.6 mL). The reaction stirred at room temperature for 1.5 hours. Then the reaction was diluted with brine and was extracted with ethyl acetate. The organic layer was dried with sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified via column chromatography using a gradient of 100% hexanes, 3:1 hexanes:ethyl acetate, and 100% ethyl acetate with 1% triethylamine throughout to afford V74 (503 mg, 99%) as a clear-yellow residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 8.42 (d, J=8.0 Hz, 1H), 7.45 (d, J=7.5 Hz, 1H), 7.34-7.19 (m, 2H), 4.69 (s, 1H), 3.15 (s, 3H), 3.05-2.89 (m, 3H), 2.82 (dd, J=13.7, 4.0 Hz, 1H), 2.78-2.66 (m, 2H), 2.03-1.94 (m, 2H), 1.98 (sextet, J=7.6 Hz, 1H), 1.62-1.50 (m, 2H), 1.39-1.33 (m, 2H), 1.08-0.98 (m, 1H), 0.84 (t, J=7.6 Hz, 3H), 0.74 (s, 1H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 169.3, 135.1, 133.7, 129.0, 125.1, 123.5, 118.5, 117.8, 116.5, 75.3, 55.8, 45.7, 45.4, 43.5, 41.2, 28.8, 25.6, 23.8, 22.4, 7.5. HRMS (ESI): calc. for C.sub.20H.sub.27N.sub.2O.sub.2 [M+H].sup.+: 327.2067, found: 327.2082.

(655) ##STR00188##

(656) Procedure for the synthesis of V75: V74 (18.2 mg, 0.056 mmol) in a 8 mL borosilicate-vial was added dichloromethane (0.5 mL) and triethylamine (16.0 μL, 0.112 mmol). The reaction was cooled to 0° C., then 3-bromobenzoyl chloride (8.0 μL, 0.061 mmol) and 4-dimethylaminopyridine in dichloromethane was added to the reaction mixture. The reaction slowly warmed to room temperature and reacted for 3 hours. Upon completion, the reaction quenched with brine, extracted with dichloromethane, and dried with sodium sulfate. The organic layer was filtered, concentrated in vacuo, and crude product was purified via column chromatography using a gradient of 100% hexanes to 3:1 hexanes:ethyl acetate to afford V75 (17 mg, 59%) as a white-brown solid. .sup.1H NMR: (400 MHz, CD.sub.3CN at 65° C.) δ 8.38 (dt, J=8.2, 0.8 Hz, 1H), 7.52-7.44 (m, 3H), 7.39 (td, J=7.7, 1.1 Hz, 1H), 7.27 (td, J=7.5, 1.0 Hz, 1H), 7.13 (s, 1H), 7.10 (t, J=8.0 Hz, 1H), 6.74 (d, J=8.0 Hz, 1H), 4.54 (d, J=1.3 Hz, 1H), 3.64 (m, 1H), 3.52-3.39 (m, 2H), 3.29 (s, 3H), 3.16 (m, 1H), 2.94 (d, J=17.6 Hz, 1H), 2.71 (dt, J=14.0, 4.9 Hz, 1H), 2.36 (dd, J=17.6, 1.3 Hz, 1H), 2.05 (m, 1H), 1.90 (m, 1H), 1.68-1.57 (m, 4H), 0.89 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CD.sub.3CN at 65° C.) δ 172.7, 170.4, 136.4, 134.9, 133.0, 131.4, 130.6, 130.4, 126.6, 126.1, 125.0, 123.0, 120.6, 119.5, 117.2, 75.8, 75.8, 56.8, 51.6, 50.2, 44.4, 41.8, 31.6, 27.3, 23.5, 22.5, 8.2. HRMS (ESI): calc. for C.sub.27H.sub.30BrN.sub.2O.sub.3 [M+H].sup.+: 509.1434, found: 509.1447. MP: 68-70° C.

(657) ##STR00189##

(658) Procedure for the synthesis of V78: V74 (36.0 mg, 0.110 mmol) was added to a round-bottom flask. Anhydrous N, N-dimethylformamide (2.8 mL), potassium carbonate (61.0 mg, 0.440 mmol), and 4-nitrobenzyl bromide (48.0 mg, 0.220 mmol) were added sequentially at room temperature. The reaction stirred at this temperature for ˜2 hours, upon completion, the reaction was quenched with brine and extracted with dichloromethane. The crude extract was dried with sodium sulfate, filtered, concentrated in vacuo, and purified via column chromatography using a gradient of 100% hexanes to 7:1 hexanes:ethyl acetate with 1% triethylamine throughout to afford V78 (26.3 mg, 52%) as a brown solid. .sup.1H NMR: (400 MHz, CD.sub.3CN at 65° C.) 8.40 (d, J=8.1 Hz, 1H), 7.54 (d, J=8.4 Hz, 2H), 7.35 (ddd, J=7.5, 1.0 Hz, 1H), 7.17 (d, J=7.9 Hz, 1H), 7.04 (dd, J=7.4 Hz, 1H), 6.73 (d, J=8.4 Hz, 2H), 4.63 (s, 1H), 3.63 (d, J=14.6 Hz, 1H), 3.23 (s, 3H), 3.18 (d, J=14.6 Hz, 1H), 3.10-2.95 (m, 2H), 2.94-2.86 (m, 2H), 2.59 (td, J=12.1, 4.6 Hz, 1H), 2.47 (dd, J=12.5, 4.6 Hz, 1H), 2.35 (d, J=17.4 Hz, 1H), 2.19 (dt, J=14.7, 3.3 Hz, 1H), 2.02 (m, 1H), 1.75 (sextet, J=7.6 Hz, 1H), 1.65 (m, 1H), 1.51 (m, 1H), 1.41-1.26 (m, 2H), 0.93 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CD.sub.3CN at 65° C.) δ 170.7, 149.0, 147.9, 136.4, 134.9, 131.0, 130.2, 126.0, 124.6, 123.7, 120.2, 120.1, 117.2, 76.8, 58.2, 56.5, 52.1, 51.7, 45.1, 42.4, 29.0, 27.0, 22.5 (2C), 8.1. Note: The presence of overlapping signals was proven by HSQC. HRMS (ESI): calc. for C.sub.27H.sub.32N.sub.3O.sub.4 [M+H].sup.+: 462.2387, found: 462.2403. MP: 173-175° C.

(659) ##STR00190##

(660) Procedure for the synthesis of V72: Lithium aluminum hydride (135.0 mg, 3.57 mmol) was added to a flame-dried round-bottom flask containing tetrahydrofuran (7.14 mL) at 0° C. V6 (210.2 mg, 0.714 mmol) was added portion-wise at 0° C., then warmed to room temperature for approximately two minutes. The reaction was heated to 66° C. and allowed to react for 1 hour, upon completion, the reaction was quenched with 1 M NaOH (˜5-6 drops) and distilled water (˜1.0 mL). This crude mixture was filtered through a frit funnel containing celite, and the filtrate was rinsed with warm ethyl acetate. The organic layer was dried with sodium sulfate and concentrated in vacuo. Crude product was purified via column chromatography 100% hexanes to 4:1 hexanes:ethyl acetate with 1% triethylamine throughout to afford V72 (179.0 mg, 84%) as a white powder. Note: V72 is a known compound (CAS No. 19877-90-8). Spectral data below are consistent with literature..sup.7.8 1H NMR: (400 MHz, CDCl.sub.3) δ 7.79 (d, J=7.7 Hz, 1H), 7.49 (dd, J=7.5 Hz, 1H), 7.23-7.16 (m, 2H), 5.74-5.34 (m, 2H), 3.21 (s, 1H), 3.15 (dd, J=13.1, 6.0 Hz, 1H), 3.01 (td, J=12.7, 6.2 Hz, 1H), 2.89 (m, 1H), 2.47-2.41 (m, 2H), 2.26 (td, J=12.0, 2.9 Hz, 1H), 2.12 (dd, J=14.1, 4.6 Hz, 1H), 1.96 (sextet, J=7.5 Hz, 1H), 1.62 (dd, J=14.2, 8.6 Hz, 1H), 1.41 (dd, J=13.6, 9.6 Hz, 1H), 1.34-1.21 (m, 3H), 0.84 (t, J=7.5 Hz, 3H), 0.76 (td, J=13.7, 3.8 Hz, 1H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 136.9, 132.7, 128.7, 121.2, 120.1, 118.1, 112.4, 105.2, 76.5, 58.5, 50.7, 44.3, 43.0, 36.7, 28.5, 24.8, 20.4, 16.9, 7.7. HRMS (ESI): calc. for C.sub.19H.sub.25N.sub.2O [M+H].sup.+: 297.1961, found: 297.1966. MP: 83-85° C.

(661) ##STR00191##

(662) Procedure for the synthesis of DHE: V72 (70.2 mg, 0.237 mmol) was added to a round-bottom flask. Anhydrous dichloromethane (2.4 mL), triethylsilane (2.1 mL, 13.0 mmol), and trifluoroacetic acid (0.472 mL, 6.2 mmol) were added to the flask sequentially. The reaction stirred for ˜2 hours, upon completion, the reaction was quenched with saturated aqueous sodium bicarbonate and brine. This mixture was extracted with dichloromethane, dried with sodium sulfate, filtered, and the organic layer was concentrated in vacuo. The crude product was purified via column chromatography 100% hexanes to 5:1 hexanes:ethyl acetate with 1% triethylamine throughout to afford V73 (53.0 mg, 80%) as a colorless residue. Note: V73 is a known compound (CAS No. 65026-49-5). The spectral data below are consistent with literature..sup.8 1H NMR: (400 MHz, CDCl.sub.3) δ 7.55 (m, 1H), 7.32 (ddd, J=8.0, 1.2, 0.8 Hz, 1H), 7.22 (td, J=7.5, 1.2 Hz, 1H), 7.16 (td, J=7.6, 1.2 Hz, 1H), 4.12 (ddd, J=11.8, 5.9, 1.9 Hz, 1H), 3.89 (s, 1H), 3.77 (td, J=12.0, 5.2 Hz, 1H), 3.39-3.25 (m, 2H), 3.03 (dddd, J=15.8, 11.1, 6.9, 2.3 Hz, 1H), 2.65-2.55 (m, 2H), 2.48 (td, J=12.6, 3.1 Hz, 1H), 2.17 (sextet, J=7.6 Hz, 1H), 2.03-1.73 (m, 3H), 1.58 (sextet, J=7.5 Hz, 1H), 1.40 (dq, J=13.0, 3.1 Hz, 1H), 1.32 (m, 1H), 1.09 (td, J=13.3, 4.1 Hz, 1H), 0.97 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 136.4, 132.9, 128.2, 120.6, 119.4, 118.2, 109.4, 104.5, 59.3, 51.4, 44.7, 38.6, 34.2, 32.0, 29.1, 24.0, 21.0, 17.3, 7.7. HRMS (ESI): calc. for C.sub.19H.sub.25N.sub.2 [M+H].sup.+: 281.2012, found: 281.2008.

(663) ##STR00192##

(664) General Procedure for the synthesis of V68-V71: V73 (55.6 mg, 0.198 mmol) was added to a flame-dried round-bottom flask and subsequently dissolved in a 2:1 tetrahydrofuran:water solution (12.0 mL). Methyl propiolate (26.0 μL, 0.297 mmol) was added dropwise and the reaction was stirred at room temperature. The reaction was equipped with a reflux condenser and heated to 66° C. for 2.5 hours. Upon completion, the reaction was washed with saturated aqueous brine, and extracted with ethyl acetate. The organic layer was dried with sodium sulfate, filtered, and concentrated in vacuo. Crude product was purified via column chromatography using a gradient of 100% hexanes to 1:1 hexanes:ethyl acetate to afford V68 (58.0 mg, 76%) as a yellow residue.

(665) ##STR00193##

(666) Yield: 76%; 58.0 mg of V68 as a yellow residue. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.55-7.50 (m, 2H), 7.30 (d, J=8.2 Hz, 1H), 7.23 (td, J=7.5, 1.1 Hz, 1H), 7.13 (td, J=7.5, 0.9 Hz, 1H), 4.74 (d, J=13.3 Hz, 1H), 4.68 (s, 1H), 4.24 (ddd, J=12.3, 7.5, 3.4 Hz, 1H), 3.88 (ddd, J=12.3, 9.6, 2.6 Hz, 1H), 3.74-3.62 (m, 4H), 3.37 (dd, J=14.2, 8.4 Hz, 1H), 3.14 (td, J=13.6, 1.6 Hz, 1H), 2.96-2.83 (m, 2H), 2.37-2.22 (m, 2H), 1.93-1.72 (m, 2H), 1.71-1.55 (m, 4H), 1.24 (m, 1H), 1.02-0.78 (m, 4H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 169.9, 151.6, 137.5, 137.4, 127.3, 122.2, 119.8, 118.6, 110.0, 109.9, 86.7, 67.2, 58.5, 56.7, 50.7, 40.1, 39.7, 32.4, 28.4, 27.2, 22.3, 21.9, 8.2. HRMS (ESI): calc. for C.sub.23H.sub.31N.sub.2O.sub.3 [M+H].sup.+: 383.2329, found: 383.2322.

(667) ##STR00194##

(668) Yield: 83%; 36.0 mg of V69 as a yellow residue. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.60-7.51 (m, 2H), 7.31 (d, J=8.1 Hz, 1H), 7.24 (td, J=8.1, 1.1 Hz, 1H), 7.15 (td, J=7.5, 1.2 Hz, 1H), 4.79 (d, J=13.3 Hz, 1H), 4.20 (ddd, J=12.2, 7.5, 4.1 Hz, 1H), 4.11 (s, 1H), 3.91 (ddd, J=12.2, 7.5, 3.5 Hz, 1H), 3.74-3.67 (m, 4H), 3.39 (dd, J=14.0, 8.1 Hz, 1H), 3.24-3.16 (m, 4H), 3.03-2.87 (m, 2H), 2.38-2.18 (m, 2H), 1.80 (sextet, J=7.5 Hz, 1H), 1.72-1.53 (m, 4H), 1.24 (m, 1H), 0.97-0.78 (m, 4H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 169.9, 151.5, 137.5, 134.8, 127.2, 122.1, 119.6, 118.4, 111.8, 109.9, 86.4, 76.4, 58.8, 56.6, 56.2, 50.7, 40.5, 39.6, 33.1, 28.9, 28.4, 22.2 (2C), 8.3. HRMS (ESI): calc. for C.sub.24H.sub.33N.sub.2O.sub.3 [M+H].sup.+: 397.2486, found: 397.2500.

(669) ##STR00195##

(670) Yield: 67%; 41.8 mg of V70 as a yellow residue. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.58 (d, J=13.3 Hz, 1H), 7.53 (dt, J=7.8, 1.0 Hz, 1H), 7.31 (dt, J=8.0, 0.9 Hz, 1H), 7.23 (ddd, J=8.0, 7.0, 1.1 Hz, 1H), 7.13 (ddd, J=8.0, 7.0, 1.1 Hz, 1H), 4.78 (d, J=13.3 Hz, 1H), 4.33 (s, 1H), 4.21 (ddd, J=12.4, 7.5, 5.0 Hz, 1H), 3.95 (ddd, J=12.4, 7.6, 4.5 Hz, 1H), 3.74-3.68 (m, 4H), 3.51 (septet, J=6.0 Hz, 1H), 3.36 (ddd, J=14.0, 8.6, 1.3 Hz, 1H), 3.16 (t, J=13.5 Hz, 1H), 2.95 (q, J=13.0 Hz, 2H), 2.34 (ddd, J=14.1, 7.8, 2.1 Hz, 1H), 2.24 (ddd, J=13.5, 7.7, 6.1 Hz, 1H), 1.81 (sextet, J=7.6 Hz, 1H), 1.70-1.51 (m, 5H), 1.14 (d, J=6.0 Hz, 3H), 0.91-0.87 (m, 7H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) 169.8, 151.5, 137.3, 136.6, 127.2, 121.8, 119.4, 118.4, 110.6, 109.7, 86.4, 71.7, 68.3, 58.1, 56.3, 50.7, 40.6, 39.4, 33.3, 29.1, 28.9, 23.8, 22.1 (2C), 21.4, 8.3. HRMS (ESI): calc. for C.sub.26H.sub.37N.sub.2O.sub.3 [M+H].sup.+: 425.2799, found: 425.2811.

(671) ##STR00196##

(672) Yield: 57%; 28.0 mg of V71 as a clear foam. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 7.61 (d, J=13.4 Hz, 1H), 7.46 (dt, J=7.9, 1.0 Hz, 1H), 7.34 (dt, J=8.1, 0.9 Hz, 1H), 7.24 (m, 1H), 7.17 (dd, J=8.2, 7.5 Hz, 2H), 7.12 (ddd, J=8.0, 7.0, 1.1 Hz, 1H), 6.95 (ddd, J=7.7, 7.0, 1.1 Hz, 1H), 6.86-6.84 (m, 2H), 5.13 (s, 1H), 4.75 (d, J=13.4 Hz, 1H), 4.37 (ddd, J=12.2, 7.5, 3.8 Hz, 1H), 3.99 (ddd, J=12.2, 7.4, 3.1 Hz, 1H), 3.78 (s, 3H), 3.59 (dt, J=13.9, 2.9 Hz, 1H), 3.45 (dd, J=14.1, 7.5 Hz, 1H), 2.82 (ddd, J=14.4, 7.6, 6.4 Hz, 1H), 2.71-2.62 (m, 2H), 2.49 (ddd, J=14.1, 8.3, 5.1 Hz, 1H), 2.31 (dd, J=14.4, 8.5 Hz, 1H), 1.95 (sextet, J=7.5 Hz, 1H), 1.88-1.67 (m, 3H), 1.37-1.22 (m, 2H), 1.05-0.83 (m, 4H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 169.8, 158.7, 151.1, 137.5, 134.6, 129.5, 127.2, 122.6, 122.2, 119.6, 119.6, 118.7, 111.4, 109.9, 87.3, 77.4, 58.9, 56.7, 50.8, 40.6, 39.7, 32.9, 28.9, 28.2, 22.0 (2C), 8.3. HRMS (ESI): calc. for C.sub.29H.sub.35N.sub.2O.sub.3 [M+H].sup.+: 459.2642, found: 459.2651. MP: 70-72° C.

(673) ##STR00197##

(674) Procedure for the synthesis of V54: V6 (3.53 g, 12.0 mmol) was reacted in a flame-dried microwave flask in 7 equal portions portions. Each portion was dissolved in ethanol (8.5 mL) and a 5.0 M aqueous potassium hydroxide solution was added (5.0 mL). The resultant reaction mixture was subjected to microwave irradiation at 180° C. for twenty minutes. These cycles (˜7) were combined and acidified to pH ˜5-6, extracted with dichloromethane, and extract was dried with sodium sulfate. Crude extract was filtered, concentrated in vacuo, and purified via column chromatography 99:1 dichloromethane:triethylamine to 94.5:4.5:1.0 dichloromethane:methanol:triethylamine to afford V54 (3.80 g, 99%) as a white foam. .sup.1H NMR: (400 MHz, d.sub.6-DMSO) δ 12.59 (s, 1H), 9.86 (s, 1H), 7.46 (d, J=8.1 Hz, 1H), 7.36 (d, J=7.5 Hz, 1H), 7.03 (dd, J=7.5 Hz, 1H), 6.95 (dd, J=7.4 Hz, 1H), 3.40 (s, 1H), 3.02-2.97 (m, 2H), 2.81-2.72 (m, 2H), 2.60-2.52 (m, 2H), 2.41 (td, J=11.7, 2.7 Hz, 1H), 2.04 (dq, J=15.0, 7.5 Hz, 1H), 1.95-1.70 (m, 3H), 1.68-1.48 (m, 3H), 1.06 (t, J=7.5 Hz, 3H)..sup.13C NMR: (100 MHz, d6-DMSO) δ 174.1, 136.6, 132.1, 126.1, 120.8, 118.5, 117.2, 111.9, 110.6, 66.1, 56.0, 53.2, 39.2, 38.9, 31.4, 31.1, 21.7, 21.5, 8.4. HRMS (ESI): calc. for C.sub.19H.sub.25N.sub.2O.sub.2 [M+H].sup.+: 313.1911, found: 313.1918. MP: 204-206° C., lit. 204-206° C..sup.9

(675) ##STR00198##

(676) General Procedure for the synthesis of V5, V10-V11, V19, V23-V26, V51-V53, & V90-V91: V54 (181.2 mg, 0.580 mmol) was added to a flame-dried round-bottom flask and dissolved in anhydrous dichloromethane (4.8 mL). The reaction was cooled to 0° C. and triethylamine (0.162 mL, 1.16 mmol) was added dropwise. After stirring for ˜5 minutes ethyl chloroformate (61 μL, 0.638 mmol) was added and the reaction stirred for ˜30 minutes. Benzyl amine (0.633 mL, 5.8 mmol) and N,N-dimethylaminopyridine (catalytic) as a 0.3 M solution in anhydrous dichloromethane were added, and the reaction warmed to room temperature. At room temperature, the reaction stirred for 3 hours and was quenched with brine when complete by thin layer chromatography. Crude reaction mixture was extracted with dichloromethane, dried with sodium sulfate, filtered, and the organic layer was concentrated in vacuo. The crude product was purified via column chromatography using a gradient of 100% hexanes to 5:1 hexanes:ethyl acetate with 1% triethylamine throughout to afford V52 (135.0 mg, 58%) as a yellowish-brown foam.

(677) ##STR00199##

(678) Yield: 58%; 135.0 mg of V52 as a yellowish-brown foam. .sup.1H NMR: (400 MHz, CDCl.sub.3) 8.06 (s, 1H), 7.50 (d, J=7.5 Hz, 1H), 7.35 (dd, J=8.1, 0.9 Hz, 1H), 7.32-7.22 (m, 3H), 7.23-7.06 (m, 4H), 6.08 (s, 1H), 4.27 (dd, J=14.6, 6.5 Hz, 1H), 3.75 (dd, J=14.6, 4.4 Hz, 1H), 3.37 (s, 1H), 3.00-2.95 (m, 2H), 2.85 (m, 1H), 2.73-2.53 (m, 3H), 2.41 (td, J=12.7, 2.2 Hz, 1H), 2.17 (d, J=14.0 Hz, 1H), 2.13-1.85 (m, 4H), 1.67-1.55 (m, 2H), 1.20 (t, J=7.6 Hz, 3H). Note: H spectrum referenced TMS at 0.00 ppm. .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 172.1, 138.4, 136.1, 133.1, 128.5, 127.9, 127.2, 126.7, 121.8, 119.5, 117.9, 111.7, 111.0, 66.6, 56.9, 54.0, 43.5, 40.7, 40.4, 33.3, 31.7, 22.2, 21.9, 8.2. HRMS (ESI): calc. for C.sub.26H.sub.32N.sub.2O.sub.3 [M+H].sup.+: 402.2540, found: 402.2550. MP: 151-153° C.

(679) ##STR00200##

(680) Yield: 91%; 152.0 mg of V51 as a yellow-white foam. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 8.08 (s, 1H), 7.46 (d, J=7.6 Hz, 1H), 7.32 (d, J=7.9 Hz, 1H), 7.13 (td, J=7.4, 0.9 Hz, 1H), 7.08 (td, J=7.7, 1.2 Hz, 1H), 5.64 (d, J=7.2 Hz, 1H), 4.95 (d, J=7.4 Hz, 1H), 3.98 (p, J=6.9 Hz, 1H), 3.86 (q, J=6.9 Hz, 1H), 3.34 (s, 1H), 3.08-2.83 (m, 3H), 2.73-2.53 (m, 3H), 2.40 (t, J=11.4 Hz, 1H), 2.13-1.85 (m, 7H), 1.79 (dt, J=12.8, 6.3 Hz, 1H), 1.72-1.24 (m, 13H), 1.16 (t, J=7.6 Hz, 4H), 1.01 (dt, J=12.7, 6.5 Hz, 1H). Note: Spectrum represents a 2:1 ratio of amide rotamers. .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 172.0, 158.2, 136.2, 133.2, 126.7, 121.7, 119.4, 117.9, 111.8, 111.1, 66.8, 56.9, 54.1, 51.8, 51.0, 40.9, 40.4, 33.7, 33.6, 33.3, 32.9, 32.7, 31.6, 23.7, 23.8, 23.7, 22.3, 22.0, 8.2. Note: Spectrum represents a mixture of rotamers. HRMS (ESI): calc. for C.sub.24H.sub.34N.sub.3O [M+H].sup.+: 380.2696, found: 380.2710. MP: 64-66° C.

(681) ##STR00201##

(682) Yield: 99%; 63.6 mg of V11 as a greenish-white foam. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 8.04 (s, 1H), 7.45 (d, J=7.6 Hz, 1H), 7.31 (dd, J=8.1, 0.9 Hz, 1H), 7.13 (td, J=8.1, 1.3 Hz, 1H), 7.07 (td, J=7.6, 1.2 Hz, 1H), 5.55 (s, 1H), 5.16 (t, J=4.7 Hz, 1H), 3.35 (s, 1H), 3.12 (q, J=7.1 Hz, 3H), 3.07-2.82 (m, 4H), 2.72-2.54 (m, 3H), 2.39 (td, J=11.8, 2.5 Hz, 1H), 2.13 (d, J=13.9 Hz, 1H), 2.05-1.82 (m, 4H), 1.64-1.53 (m, 2H), 1.48-1.38 (m, 3H), 1.37-1.24 (m, 3H), 1.21-1.10 (m, 6H), 0.90 (t, J=7.3 Hz, 3H), 0.84-0.77 (m, 2H). Note: Spectrum represents a 2:1 ratio of amide rotamers. .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 172.4, 159.1, 136.2, 133.3, 126.7, 121.8, 119.5, 117.9, 111.7, 111.1, 66.7, 57.0, 54.1, 40.8, 40.4, 40.1, 39.2, 33.6, 32.6, 31.5, 31.3, 22.3, 22.1, 20.2, 20.1, 14.0, 13.8, 8.3. Note: Spectrum represents a mixture of rotamers. HRMS (ESI): calc. for C.sub.23H.sub.34N.sub.3O [M+H].sup.+: 368.2696, found: 368.2679. MP: 47-49° C.

(683) ##STR00202##

(684) Yield: 52%; 73.0 mg of V24 as a brown residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.93 (s, 1H), 7.47 (d, J=7.8 Hz, 1H), 7.32 (dt, J=8.1, 0.9 Hz, 1H), 7.15 (ddd, J=8.2, 7.1, 1.2 Hz, 1H), 7.09 (ddd, J=7.8, 7.1, 1.2 Hz, 1H), 6.11 (s, 1H), 3.76 (ddd, J=17.8, 5.9, 2.5 Hz, 1H), 3.42-3.32 (m, 2H), 3.05-3.02 (m, 2H), 2.94 (dd, J=17.7, 14.4 Hz, 1H), 2.68 (d, J=15.1 Hz, 1H), 2.65-2.53 (m, 2H), 2.41 (td, J=11.9, 2.8 Hz, 1H), 2.19 (d, J=14.1 Hz, 1H), 2.11 (m, 1H), 2.05-1.91 (m, 3H), 1.85 (m, 1H), 1.67-1.56 (m, 2H), 1.17 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 172.2, 136.1, 132.9, 126.7, 121.9, 119.5, 117.9, 111.8, 111.1, 79.9, 71.2, 66.8, 56.9, 54.1, 40.5, 40.5, 33.3, 31.8, 28.9, 22.2, 22.0, 8.2. HRMS (ESI): calc. for C.sub.22H.sub.28N.sub.3O [M+H].sup.+: 350.2227, found: 350.2232.

(685) ##STR00203##

(686) Yield: 77%; 209.0 mg of V53 as a brown residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 8.08-8.01 (m, 2H), 7.45 (d, J=Hz, 2H), 7.30 (dd, J=7.8, 4.3 Hz, 2H), 7.22-7.11 (m, 7H), 7.11-7.04 (m, 5H), 6.87 (dd, J=7.0, 3.7 Hz, 2H), 4.81 (d, J=16.8 Hz, 1H), 4.55 (d, J=14.7 Hz, 1H), 3.92 (d, J=14.7 Hz, 1H), 3.72 (d, J=16.8 Hz, 1H), 3.34 (d, J=2.2 Hz, 1H), 3.27 (s, 1H), 3.03-2.84 (m, 6H), 2.70 (s, 3H), 2.68-2.51 (m, 3H), 2.42 (s, 4H), 2.40-2.20 (m, 5H), 2.13 (m, 1H), 2.05-1.89 (m, 3H), 1.76 (m, 1H), 1.64-1.46 (m, 3H), 1.21-1.11 (m, 5H). Note: .sup.1H spectrum referenced TMS at 0.00 ppm. Spectrum represents a 1:1 ratio of amide rotamers. Rotamers verified using a known method..sup.9 13C NMR: (100 MHz, CDCl.sub.3) δ 172.9, 172.6, 137.7, 137.6, 136.3, 136.2, 133.3, 128.6, 128.4, 127.9, 127.2, 127.1, 126.8, 126.6, 126.4, 121.6, 121.6, 119.4, 119.3, 117.8, 117.6, 112.0, 111.5, 111.1, 111.0, 67.1, 66.7, 57.1, 57.0, 54.7, 54.4, 54.2, 50.5, 41.3, 41.1, 35.9, 34.6, 34.5, 34.4, 34.1, 32.8, 31.2, 31.1, 22.4, 22.2, 22.0, 8.3, 8.3. HRMS (ESI): calc. for C.sub.27H.sub.34N.sub.3O [M+H].sup.+: 416.2696, found: 416.2709.

(687) ##STR00204##

(688) Yield: 76%; 58.3 mg of V10 as a dark-red foam. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 8.26 (dd, J=8.0, 1.2 Hz, 1H), 7.99 (s, 1H), 7.83 (s, 1H), 7.47 (d, J=7.8 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.16 (ddd, J=8.3, 7.0, 1.2 Hz, 1H), 7.10 (ddd, J=8.0, 7.5, 0.9 Hz, 1H), 6.98 (td, J=7.8, 1.5 Hz, 1H), 6.87 (td, J=7.8, 1.4 Hz, 1H), 6.80 (dd, J=8.1, 1.1 Hz, 1H), 3.82 (s, 3H), 3.43 (s, 1H), 3.12-2.93 (m, 4H), 2.75-2.59 (m, 2H), 2.45 (td, J=11.6, 2.7 Hz, 1H), 2.20-2.00 (m, 5H), 1.68 (dd, J=13.9, 3.6 Hz, 2H), 1.23 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 170.8, 148.0, 136.2, 132.9, 127.8, 126.8, 123.5, 121.9, 121.0, 119.9, 119.6, 118.0, 112.3, 111.1, 109.9, 66.8, 57.1, 55.7, 54.3, 42.0, 40.9, 32.5, 32.0, 22.5, 22.1, 8.4. HRMS (ESI): calc. for C.sub.26H.sub.32N.sub.3O.sub.2 [M+H].sup.+: 418.2489, found: 418.2492. MP: 57-59° C.

(689) ##STR00205##

(690) Yield: 82%; 151.0 mg of V26 as a yellow foam. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.98 (s, 1H), 7.47 (d, J=7.5 Hz, 1H), 7.32 (d, J=8.0 Hz, 1H), 7.15 (ddd, J=8.0, 7.1, 1.3 Hz, 1H), 7.10 (td, J=7.7, 7.4, 1.2 Hz, 1H), 3.51-3.41 (m, 2H), 3.41-3.27 (m, 4H), 3.27-3.15 (m, 2H), 3.09 (ddd, J=11.6, 6.8, 3.4 Hz, 1H), 3.05-2.97 (m, 2H), 2.87 (m, 1H), 2.70-2.53 (m, 4H), 2.44-2.33 (m, 2H), 2.25 (sextet, J=7.6 Hz, 1H), 2.07-1.82 (m, 3H), 1.68-1.53 (m, 2H), 1.19 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 171.4, 136.2, 133.4, 126.9, 121.9, 119.7, 118.0, 112.0, 111.1, 67.0, 66.7, 66.6, 57.2, 54.5, 46.8, 41.6, 41.2, 33.9, 33.8, 31.4, 22.4, 22.2, 8.4. HRMS (ESI): calc. for C.sub.23H.sub.32N.sub.3O.sub.2 [M+H].sup.+: 382.2489, found: 382.2496. MP: 65-67° C.

(691) ##STR00206##

(692) Yield: 62%; 72.0 mg of V23 as an off-white powder. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.96 (s, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.30 (d, J=7.8 Hz, 1H), 7.12 (dd, J=8.1, 6.4 Hz, 1H), 7.07 (dd, J=7.4, 7.1 Hz, 1H), 3.34 (s, 1H), 3.27 (ddd, J=14.8, 9.2, 6.2 Hz, 1H), 3.10 (m, 1H), 3.04-2.97 (m, 2H), 2.90 (m, 1H), 2.78 (ddd, J=14.8, 9.2, 5.7 Hz, 1H), 2.70-2.62 (m, 2H), 2.58 (td, J=11.1, 3.7 Hz, 1H), 2.37 (td, J=11.9, 2.4 Hz, 1H), 2.34-2.18 (m, 3H), 2.12 (m, 1H), 2.00-1.85 (m, 2H), 1.65-1.49 (m, 2H), 1.36-1.23 (m, 2H), 1.23-1.08 (m, 7H), 1.05-0.86 (m, 2H), 0.81 (t, J=6.7, 3H), 0.67 (t, J=7.4 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 172.2, 136.3, 133.4, 126.9, 121.7, 119.4, 117.8, 112.1, 111.0, 67.1, 57.2, 54.3, 48.7, 46.1, 41.2, 34.5, 33.3, 31.3, 30.9, 29.9, 22.5, 22.2, 20.5, 19.9, 14.0, 13.6, 8.4. HRMS (ESI): calc. for C.sub.27H.sub.42N.sub.3O [M+H].sup.+: 424.3322, found: 424.3301. MP: 110-112° C.

(693) ##STR00207##

(694) Yield: 28%; 49.0 mg of V91 as a yellow-white solid. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.95 (s, 1H), 7.54 (dt, J=7.1, 1.8 Hz, 1H), 7.46 (d, J=7.9 Hz, 1H), 7.39 (s, 1H), 7.32 (dd, J=7.9, 0.7 Hz, 1H), 7.16 (ddd, J=8.3, 7.4, 1.2 Hz, 1H), 7.11 (ddd, J=7.9, 7.0, 1.2 Hz, 1H), 7.03-6.92 (m, 2H), 5.92 (s, 1H), 4.15 (dd, J=14.9, 7.0 Hz, 1H), 3.50 (dd, J=14.9, 4.6 Hz, 1H), 3.36 (s, 1H), 3.02-2.91 (m, 2H), 2.80 (m, 1H), 2.68-2.51 (m, 3H), 2.39 (td, J=12.0, 2.6 Hz, 1H), 2.28 (d, J=14.0 Hz, 1H), 2.11-1.79 (m, 3H), 1.66-1.54 (m, 2H), 1.19 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 172.3, 140.9, 136.8, 136.4, 136.2, 133.2, 130.3, 127.2, 126.7, 122.0, 119.8, 118.0, 111.8, 111.1, 94.5, 66.8, 57.1, 54.2, 42.9, 40.9, 40.7, 34.0, 31.7, 22.3, 22.1, 8.3. HRMS (ESI): calc. for C.sub.26H.sub.31IN.sub.3O [M+H].sup.+: 528.1506, found: 528.1515. MP: 140-142° C.

(695) ##STR00208##

(696) Yield: 62%; 72.0 mg of V90 as a yellow-green residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 8.02 (s, 1H), 7.45 (d, J=7.7 Hz, 1H), 7.32 (d, J=8.0 Hz, 1H), 7.13 (td, J=7.4, 0.8 Hz, 1H), 7.08 (td, J=7.3, 0.8 Hz, 1H), 5.81 (s, 1H), 3.36 (s, 1H), 3.05-2.97 (m, 2H), 2.89 (m, 1H), 2.67 (m, 1H), 2.59 (td, J=11.4, 3.1 Hz, 1H), 2.49 (d, J=14.0 Hz, 1H), 2.40 (td, J=12.0, 2.5 Hz, 1H), 2.26 (octet, J=3.8 Hz, 1H), 2.17 (d, J=14.0 Hz, 1H), 2.09-1.89 (m, 3H), 1.85 (m, 1H), 1.64-1.61 (m, 2H), 1.16 (t, J=7.6 Hz, 3H), 0.50 (m, 1H), 0.40 (m, 1H), 0.12 (m, 1H), 0.03 (m, 1H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 173.9, 136.2, 133.1, 126.7, 121.9, 119.6, 117.9, 111.7, 111.2, 66.8, 57.0, 54.2, 40.6, 40.5, 33.8, 31.5, 22.4, 22.1, 22.0, 8.3, 6.3, 6.0. HRMS (ESI): calc. for C.sub.22H.sub.30N.sub.3O [M+H].sup.+: 352.2383, found: 352.2396.

(697) ##STR00209##

(698) Yield: 93%; 101.0 mg of V25 as a yellow-white foam. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 8.16 (s, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.13 (dd, J=8.3, 7.2 Hz, 1H), 7.07 (dd, J=8.0, 7.2 Hz, 1H), 6.47 (s, 1H), 3.43 (s, 1H), 3.34 (ddd, J=11.1, 6.4, 3.5 Hz, 1H), 3.24 (ddd, J=11.1, 6.7, 3.2 Hz, 1H), 3.13-2.91 (m, 5H), 2.82-2.59 (m, 3H), 2.48-2.38 (m, 2H), 2.33 (d, J=13.9 Hz, 1H), 2.10-1.88 (m, 3H), 1.79 (m, 1H), 1.65-1.58 (m, 2H), 1.14 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) 173.4, 136.5, 132.1, 126.5, 122.2, 119.8, 117.9, 111.5, 111.3, 67.2, 61.9, 56.9, 54.6, 42.4, 40.6, 40.3, 34.0, 31.8, 21.7, 21.6, 8.3. HRMS (ESI): calc. for C.sub.21H.sub.30N.sub.3O.sub.2 [M+H].sup.+: 356.2333, found: 356.2348. MP: 61-63° C.

(699) ##STR00210##

(700) Yield: 39%; 12.7 mg of V19 as a white-brown solid. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.92 (s, 1H), 7.46 (d, J=7.4 Hz, 2H), 7.29 (d, J=8.1 Hz, 1H), 7.13 (td, J=7.9, 1.4 Hz, 1H), 7.09 (td, J=7.7, 0.9 Hz, 1H), 6.75 (s, 2H), 6.62 (s, 1H), 3.41 (s, 1H), 3.11-2.91 (m, 3H), 2.77-2.68 (m, 2H), 2.64 (td, J=11.2, 2.8 Hz, 1H), 2.45 (dd, J=13.3, 11.3 Hz, 1H), 2.36 (d, J=14.2 Hz, 1H), 2.17 (s, 6H), 2.15-1.90 (m, 4H), 1.64 (ddt, J=13.4, 9.7, 5.4 Hz, 2H), 1.20 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 170.9, 138.5, 138.0, 136.3, 133.0, 126.9, 125.7, 122.2, 119.9, 118.1, 117.4, 112.4, 111.2, 67.2, 57.0, 54.2, 42.8, 41.1, 33.9, 32.0, 29.9, 22.4, 22.3, 21.5, 8.4. HRMS (ESI): calc. for C.sub.27H.sub.34N.sub.3O [M+H].sup.+: 416.2696, found: 416.2712. MP: 164-166° C.

(701) ##STR00211##

(702) Procedure for the synthesis of V5: V54 (32.8 mg, 0.105 mmol) was added to a flame-dried round-bottom flask and dissolved in anhydrous dichloromethane (2.6 mL). 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (24.0 μL, 0.136 mmol) was added dropwise and the reaction stirred for ˜5 minutes. Over a period of 20 minutes, 3,5 dimethoxyaniline (21.0 mg, 0.136 mmol) as a 0.3 M solution in anhydrous dichloromethane was added and the reaction proceeded for 72 hours. Upon completion, the reaction was quenched with deionized water, extracted with ethyl acetate, and crude extract dried with sodium sulfate. The organic layer was filtered, concentrated in vacuo, and purified via column chromatography using a gradient of 100% hexanes to 3:1 hexanes:ethyl acetate with 1% triethylamine throughout to yield V5 (10.1 mg, 21%) as a white-brown residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 8.15 (s, 1H), 7.90 (s, 1H), 7.42 (d, J=7.7 Hz, 1H), 7.30 (d, J=8.0 Hz, 1H), 7.13 (td, J=7.3, 1.2 Hz, 1H), 7.07 (td, J=7.6, 0.9 Hz, 1H), 6.52 (d, J=2.1 Hz, 2H), 6.12 (t, J=2.1 Hz, 1H), 3.69 (s, 6H), 3.43 (s, 1H), 3.11-3.02 (m, 2H), 2.95 (m, 1H), 2.78-2.58 (m, 3H), 2.46 (dd, J=11.6 Hz, 1H), 2.30-2.18 (m, 2H), 2.10-1.90 (m, 5H), 1.76-1.55 (m, 2H), 1.19 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 171.0, 161.0, 140.1, 136.3, 132.7, 126.9, 122.1, 119.8, 118.1, 112.3, 111.1, 97.6, 96.5, 67.2, 56.9, 55.6, 55.5, 54.2, 43.1, 41.0, 33.2, 32.6, 22.3, 22.2, 8.4. HRMS (ESI): calc. for C.sub.27H.sub.34N.sub.3O.sub.3 [M+H].sup.+: 448.2595, found: 448.2595.

(703) ##STR00212##

(704) General Procedure for the synthesis of V56-V57, V59 & V86-V87: V52 (45.4 mg, 0.113 mmol) was added to a flame-dried round-bottom flask and dissolved in anhydrous dichloromethane (4.52 mL). The reaction was cooled to −41° C. in an acetonitrile dry ice bath, and trifluoroacetic acid (0.155 mL, 1.921 mmol) was added. This reaction mixture reacted for ˜5-10 minutes, then meta-chloroperoxybenzoic acid (20.0 mg, 0.113 mmol) was added as a 0.3 M solution in anhydrous dichloromethane. The reaction stirred for 8 hours, then the reaction was quenched with 3 M aqueous ammonium hydroxide. Crude reaction was extracted with dichloromethane, washed with brine, and the organic layer was dried with sodium sulfate. The organic layer was concentrated in vacuo and crude product was purified via column chromatography using a gradient of 100% hexanes to 4:1 hexanes:ethyl acetate with 1% triethylamine to afford V56 (20.0 mg, 44%) as a light-green foam.

(705) ##STR00213##

(706) Yield: 44%; 20.0 mg of V56 as a light-green foam. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 9.40 (s, 1H), 7.48 (dd, J=7.6, 1.4 Hz, 1H), 7.30-7.21 (m, 3H), 7.18-7.10 (m, 3H), 7.08-6.98 (m, 2H), 4.46 (d, J=14.8 Hz, 1H), 3.81 (d, J=14.8 Hz, 1H), 3.30 (ddd, J=11.7, 6.9, 4.9 Hz, 1H), 3.20-3.10 (m, 2H), 2.91-2.75 (m, 2H), 2.62 (dt, J=12.8, 4.4 Hz, 1H), 2.54 (ddd, J=13.2, 9.5, 3.7 Hz, 1H), 2.36 (d, J=16.9 Hz, 1H), 2.01 (m, 1H), 1.76 (m, 1H), 1.64-1.50 (m, 2H), 1.36-1.24 (m, 2H), 0.84 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 175.2, 137.8, 137.4, 132.5, 128.7, 128.1, 126.8, 126.0, 122.3, 119.1, 118.2, 114.3, 112.1, 84.5, 49.9, 49.6, 44.8, 44.3, 43.6, 32.8, 27.2, 22.3, 17.7, 9.6. HRMS (ESI): calc. for C.sub.26H.sub.3N.sub.3O [M+H].sup.+: 400.2383, found: 400.2393. MP: 90-92° C.

(707) ##STR00214##

(708) Yield: 37%; 24.0 mg of V57 as an off-white foam. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 9.41 (s, 1H), 7.54-7.45 (m, 2H), 7.17 (ddd, J=8.0, 7.0, 1.3 Hz, 1H), 7.09 (ddd, J=8.0, 7.0, 1.1 Hz, 1H), 3.68 (p, J=9.7 Hz, 1H), 3.58 (ddd, J=11.7, 9.1, 4.5 Hz, 1H), 3.25-3.13 (m, 2H), 3.04-2.86 (m, 4H), 2.78 (dt, J=15.1, 4.5 Hz, 1H), 2.49 (ddd, J=14.5, 10.0, 9.0 Hz, 1H), 2.09 (d, J=16.5 Hz, 1H), 2.02 (m, 1H), 1.90-1.71 (m, 4H), 1.70-1.42 (m, 3H), 1.42-1.30 (m, 2H), 1.29-1.04 (m, 2H), 0.79 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 173.4, 137.3, 133.2, 126.3, 122.2, 119.2, 118.2, 113.3, 112.0, 83.7, 52.9, 50.1, 49.9, 45.3, 43.3, 32.4, 28.6, 28.0, 26.8, 25.3, 24.8, 22.2, 17.1, 9.7. HRMS (ESI): calc. for C.sub.24H.sub.32N.sub.3O [M+H].sup.+: 378.2540, found: 378.2546. MP: 210-212° C.

(709) ##STR00215##

(710) Yield: 43%; 27.0 mg of V59 as a light-green foam. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 9.41 (s, 1H), 7.50 (d, J=8.7 Hz, 2H), 7.16 (ddd, J=8.2, 7.0, 1.1 Hz, 1H), 7.08 (ddd, J=7.9, 7.2, 0.9 Hz, 1H), 3.39 (m, 1H), 3.25-3.06 (m, 3H), 3.06-2.93 (m, 5H), 2.85-2.78 (m, 2H), 2.19 (d, J=16.8 Hz, 1H), 2.02 (m, 1H), 1.82 (m, 1H), 1.62-1.45 (m, 2H), 1.45-1.11 (m, 2H), 0.98 (sextet, J=7.3 Hz, 2H), 0.80 (t, J=7.5 Hz, 3H), 0.59 (t, J=7.3 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 174.6, 137.3, 133.1, 126.2, 122.2, 119.2, 118.2, 113.5, 112.1, 83.5, 50.3, 50.0, 46.0, 44.4, 43.7, 41.3, 32.8, 30.0, 26.6, 22.4, 20.7, 18.3, 13.7, 9.6. HRMS (ESI): calc. for C.sub.23H.sub.32N.sub.3O [M+H].sup.+: 366.2540, found: 366.2547. MP: 170-172° C.

(711) ##STR00216##

(712) Yield: 38%; 81.0 mg of V86 as an off-white residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 9.63 (s, 1H), 7.66 (dt, J=8.1, 0.8 Hz, 1H), 7.53 (d, J=7.9 Hz, 1H), 7.20 (ddd, J=7.9, 6.9, 1.2 Hz, 1H), 7.11 (ddd, J=8.1, 6.9, 0.8 Hz, 1H), 3.94 (dd, J=17.3, 2.6 Hz, 1H), 3.61 (dd, J=17.3, 2.6 Hz, 1H), 3.47-3.34 (m, 2H), 3.25 (ddd, J=11.8, 6.2, 5.9 Hz, 1H), 3.16 (d, J=17.0 Hz, 1H), 3.01 (dt, J=12.8, 4.2 Hz, 1H), 2.94-2.79 (m, 2H), 2.31 (d, J=17.0 Hz, 1H), 2.05 (dtd, J=12.9, 4.3, 2.0 Hz, 1H), 1.98 (t, J=2.6 Hz, 1H), 1.88 (m, 1H), 1.68-1.52 (m, 2H), 1.47 (m, 1H), 1.33 (sextet, J=7.6 Hz, 1H), 0.86 (t, J=7.6 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 174.4, 137.5, 131.6, 126.0, 122.4, 119.2, 118.2, 114.4, 112.4, 83.6, 78.9, 70.8, 50.1, 49.6, 43.9, 43.7, 32.8, 29.8, 27.1, 22.1, 18.0, 9.5. HRMS (ESI): calc. for C.sub.22H.sub.26N.sub.3O [M+H].sup.+: 348.2070, found: 348.2075.

(713) ##STR00217##

(714) Yield: 35%; 25.4 mg of V87 as a green-yellow residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 9.47 (s, 1H), 7.55 (d, J=8.2 Hz, 1H), 7.51 (d, J=7.8 Hz, 1H), 7.17 (td, J=7.4, 1.0 Hz, 1H), 7.09 (dd, J=7.5 Hz, 1H), 3.53 (ddd, J=11.6, 9.1, 4.5 Hz, 1H), 3.21-3.10 (m, 2H), 3.09-2.98 (m, 2H), 2.89-2.72 (m, 2H), 2.22-2.10 (m, 2H), 1.98-1.89 (m, 1H), 1.81 (m, 1H), 1.59-1.35 (m, 4H), 1.13 (sextet, J=7.5 Hz, 1H), 0.78 (t, J=7.5 Hz, 3H), 0.55 (m, 1H), 0.39-0.22 (m, 2H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 175.5, 136.9, 133.3, 126.2, 122.1, 119.2, 118.3, 113.6, 112.2, 84.6, 50.4, 49.9, 44.5, 43.7, 33.2, 26.7, 24.7, 22.6, 20.0, 9.4, 6.8, 5.5. HRMS (ESI): calc. for C.sub.22H.sub.28N.sub.3O [M+H].sup.+: 350.2227, found: 350.2213.

(715) ##STR00218##

(716) Procedure for the synthesis of V88: Anhydrous copper sulfate (6.5 mg, 0.04 mmol) and sodium ascorbate (25.0 mg, 0.126 mmol) were added to a round-bottom flask and dissolved in a solution of tert-butanol:H.sub.2O (1:2) (2.25 mL). V86 (29.9 mg, 0.086 mmol) was added, then benzyl azide (11.0 μL, 0.09 mmol) as a solution in dichloromethane (0.180 mL) was added and the reaction was stirred for 2 hours. Upon completion, the reaction was quenched with brine, extracted with dichloromethane, and the organic layer was dried with sodium sulfate. Crude extract was filtered, concentrated in vacuo, and purified via column chromatography using a gradient of 100% hexanes, 1:1 hexanes:ethyl acetate, and 100% ethyl acetate with 1% triethylamine throughout to afford V88 (14.5 mg, 35%) as a yellow powder. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 9.03 (s, 1H), 7.40 (dd, J=8.1, 3.8 Hz, 2H), 7.21-7.14 (m, 2H), 7.12-7.04 (m, 3H), 6.80-6.71 (m, 3H), 4.67 (d, J=15.0 Hz, 1H), 4.56 (d, J=15.0 Hz, 2H), 4.09 (d, J=15.0 Hz, 1H), 3.37 (dt, J=11.8, 6.3 Hz, 1H), 3.26 (dt, J=11.8, 5.0 Hz, 1H), 3.01-2.85 (m, 3H), 2.68-2.61 (m, 2H), 2.24 (d, J=16.6 Hz, 1H), 2.04 (m, 1H), 1.82 (m, 1H), 1.56 (sextet, J=7.4 Hz, 1H), 1.43 (dd, J=13.5 Hz, 1H), 1.36-1.19 (m, 2H), 0.80 (t, J=7.4 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 173.6, 143.1, 137.2, 134.6, 133.0, 128.9, 128.7, 127.9, 126.2, 122.4, 121.5, 119.5, 118.7, 114.0, 111.8, 82.6, 52.9, 50.2, 49.8, 44.7, 43.6, 35.3, 32.3, 25.9, 21.8, 17.7, 9.7. HRMS (ESI): calc. for C.sub.29H.sub.33N.sub.6O [M+H].sup.+: 481.2710, found: 481.2731. MP: 83-85° C.

(717) ##STR00219##

(718) Procedure for the synthesis of V92: To a flame-dried round-bottom flask was added Tetrakis(triphenlyphosphine)palladium(0) (10.3 mg, 0.0089 mmol), copper(I) iodide (3.4 mg, 0.018 mmol), and iodobenzene (20.0 μL, 0.177 mmol). The resulting starting materials were dissolved in anhydrous N,N-dimethylformamide (2.0 mL), then triethylamine (22.0 μL, 0.160 mmol) was added dropwise. V86 (30.8 mg, 0.089 mmol) as a 0.6 M solution in anhydrous N,N-dimethylformamide was added and the reaction proceeded at room temperature for 4 hours. The reaction was heated to 80° C. for another 3 hours, upon completion, the reaction was quenched with deionized water. The crude reaction mixture was extracted with ethyl acetate, washed with brine, and the organic layer was dried with sodium sulfate. The organic layer was filtered, concentrated in vacuo, and the crude product was purified via column chromatography using a gradient of 100% hexanes to 4:1 hexanes:ethyl acetate with 1% triethylamine throughout to afford V92 (17.0 mg, 45%) as a brown residue.

(719) .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 9.11 (s, 1H), 7.56-7.47 (m, 2H), 7.17 (dd, J=8.2, 7.3 Hz, 1H), 7.12-7.04 (m, 3H), 6.78 (d, J=7.5 Hz, 2H), 4.05 (d, J=17.4 Hz, 1H), 3.82 (d, J=17.4 Hz, 1H), 3.41-3.22 (m, 3H), 3.11-2.93 (m, 2H), 2.90-2.75 (m, 2H), 2.28 (d, J=17.1 Hz, 1H), 2.07-1.96 (m, 1H), 1.83 (d, J=12.0 Hz, 1H), 1.64-1.40 (m, 3H), 1.36-1.12 (m, 2H), 0.82 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 174.1, 137.6, 132.1, 131.8, 128.1, 128.0, 126.4, 122.9, 122.6, 119.4, 118.4, 114.6, 112.4, 84.3, 83.4, 82.5, 50.1, 50.0, 44.2, 43.9, 32.8, 30.4, 26.9, 22.3, 18.4, 9.5. HRMS (ESI): calc. for C.sub.28H.sub.30N.sub.3O [M+H].sup.+: 424.2383, found: 424.2380.

(720) ##STR00220##

(721) Procedure for the synthesis of V94: To a flame-dried round-bottom flask containing anhydrous tetrahydrofuran (2.0 mL), was added sodium hydride (8.0 mg, 0.19 mmol, 60% dispersion in mineral oil). V56 (38.0 mg, 0.095 mmol) as a 0.2 M solution in anhydrous tetrahydrofuran was added at 0° C., and the reaction was warmed to room temperature over 12 hours. After this time, two equivalents of sodium hydride (16.0 mg, 0.38 mmol, 60% dispersion in mineral oil) was added and the reaction was heated to 66° C. for 6 hours. Once complete, the reaction was quenched with brine, extracted with ethyl acetate, and the organic layer dried with sodium sulfate. Organics were filtered, concentrated in vacuo, and purified via column chromatography using a gradient of 100% hexanes to 3:1 hexanes:cthyl acetate with 1% triethylamine throughout to afford V94 (19.0 mg, 36%) as a brown residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.62 (m, 1H), 7.23-7.13 (m, 5H), 7.10 (m, 1H), 7.04-6.95 (m, 4H), 6.88 (d, J=7.6 Hz, 3H), 4.77 (d, J=18.3 Hz, 1H), 4.31 (d, J=18.3 Hz, 1H), 4.12 (s, 2H), 3.27 (ddd, J=11.6, 8.2, 4.5 Hz, 1H), 3.19 (m, 1H), 2.99 (m, 1H), 2.87-2.69 (m, 2H), 2.61 (td, J=11.2, 1.8 Hz, 1H), 2.37 (d, J=17.9 Hz, 1H), 2.21 (d, J=17.9 Hz, 1H), 1.79-1.63 (m, 2H), 1.48 (m, 1H), 1.34 (dd, J=7.3 Hz, 1H), 1.24 (m, 1H), 1.08 (sextet, J=7.4 Hz, 1H), 0.42 (t, J=7.4 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 174.6, 138.9, 137.0, 136.7, 132.6, 129.8, 128.6, 128.1, 127.3, 127.2, 126.5, 125.8, 123.0, 119.8, 118.7, 116.1, 111.2, 85.1, 50.2, 47.7, 47.5, 45.7, 44.4, 42.5, 34.0, 31.5, 23.0, 17.6, 8.6. HRMS (ESI): calc. for C.sub.33H.sub.36N.sub.3O [M+H].sup.+: 490.2853, found: 490.2856.

(722) ##STR00221##

(723) General Procedure for the synthesis of V8-V9 & V58: V54 (1.51 g, 4.84 mmol) was added to a round-bottom flask and dissolved in anhydrous N,N-dimethylformamide (48.4 mL). The solution was cooled to 0° C., then anhydrous potassium carbonate (1.34 g, 9.69 mmol) and iodomethane (0.362 mL, 5.81 mmol) were added sequentially. The resulting reaction mixture warmed slowly to room temperature and reacted for 3 hours. Upon completion, the reaction was quenched with brine, extracted with ethyl acetate, and the organic layer was washed with deionized water three times (˜1 L). The organic layer was dried with sodium sulfate, filtered, concentrated in vacuo, and crude product purified via column chromatography using a gradient of 100% hexanes to 5:1 hexanes:ethyl acetate with 1% triethylamine throughout to afford V58 (1.18 g, 75%) as a brownish solid.

(724) ##STR00222##

(725) Yield: 75%; 1.180 g of V58 as a brownish solid. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.83 (s, 1H), 7.47 (d, J=7.8 Hz, 1H), 7.32 (d, J=8.0 Hz, 1H), 7.15 (ddd, J=8.0, 7.1, 1.3 Hz, 1H), 7.09 (td, J=8.0, 1.1 Hz, 1H), 3.49 (s, 3H), 3.38 (t, J=1.9 Hz, 1H), 3.09-2.97 (m, 3H), 2.84 (m, 1H), 2.68-2.53 (m, 2H), 2.40 (ddd, J=12.5, 11.2, 2.8 Hz, 1H), 2.11-1.86 (m, 3H), 1.82 (m, 1H), 1.67-1.55 (m, 3H), 1.18 (t, J=7.7 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 173.7, 136.1, 132.6, 126.8, 121.7, 119.4, 117.9, 112.4, 110.9, 66.3, 56.9, 54.0, 51.2, 40.4, 38.1, 32.3, 31.4, 22.2, 22.1, 8.2. HRMS (ESI): calc. for C.sub.20H.sub.27N.sub.2O.sub.2[M+H].sup.+: 327.2067, found: 327.2074. MP: 127-129° C.

(726) ##STR00223##

(727) Yield: 56%; 85.0 mg of V9 as a white-brown solid. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.85 (s, 1H), 7.48 (d, J=7.7 Hz, 1H), 7.33 (d, J=8.0 Hz, 1H), 7.16 (td, J=7.1, 1.0 Hz, 1H), 7.10 (td, J=7.4, 1.1 Hz, 1H), 5.83 (dddd, J=17.1, 10.4, 5.8, 5.0 Hz, 1H), 5.24 (dq, J=17.2, 1.4 Hz, 1H), 5.18 (dq, J=10.7, 1.4 Hz, 1H), 4.45 (ddd, J=13.2, 5.7, 1.2 Hz, 1H), 4.37 (ddd, J=13.2, 5.7, 1.2 Hz, 1H), 3.39 (s, 1H), 3.11 (d, J=14.1 Hz, 1H), 3.07-2.97 (m, 2H), 2.91 (m, 1H), 2.68-2.55 (m, 2H), 2.41 (td, J=12.6, 2.2 Hz, 1H), 2.12-1.90 (m, 4H), 1.86 (m, 1H), 1.68-1.55 (m, 2H), 1.19 (t, J=7.7 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 173.0, 136.2, 132.7, 132.5, 126.9, 121.8, 119.5, 118.3, 118.1, 112.6, 111.0, 66.3, 64.9, 57.0, 54.1, 40.6, 38.4, 32.4, 31.6, 22.3, 22.2, 8.3. HRMS (ESI): calc. for C.sub.22H.sub.29N.sub.2O.sub.2 [M+H].sup.+: 353.2224, found: 353.2214.

(728) ##STR00224##

(729) MP: 81-83° C. Yield: 49%; 26.0 mg of V8 as a yellow-brown residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.88 (s, 1H), 7.51 (d, J=7.6 Hz, 1H), 7.40-7.28 (m, 6H), 7.19 (td, J=7.6, 1.3 Hz, 1H), 7.13 (td, J=7.3, 1.1 Hz, 1H), 5.04 (d, J=12.6 Hz, 1H), 4.92 (d, J=12.6 Hz, 1H), 3.41 (s, 1H), 3.18 (d, J=14.1 Hz, 1H), 3.01-2.99 (m, 2H), 2.93 (m, 1H), 2.70-2.57 (m, 2H), 2.43 (ddd, J=12.0, 2.4 Hz, 1H), 2.14-1.91 (m, 4H), 1.85 (m, 1H), 1.70-1.56 (m, 2H), 1.19 (t, J=7.7 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 173.2, 136.2, 136.2, 132.7, 128.6, 128.4, 128.2, 126.8, 121.8, 119.5, 118.1, 112.5, 111.0, 66.3, 66.0, 57.0, 54.0, 40.6, 38.4, 32.4, 31.6, 22.3, 22.1, 8.2. HRMS (ESI): calc. for C.sub.26H.sub.31N.sub.2O.sub.2[M+H].sup.+: 403.2380, found: 403.2392.

(730) ##STR00225##

(731) General Procedure for the synthesis of V7, V55, & V79: V58 (44.8 mg, 0.137 mmol) was added to a round-bottom flask and dissolved in (3:1) chloroform:methanol (3.0 mL). To the resulting solution was added a 3M solution of cyanogen bromide (0.137 mL, 0.412 mmol) in dichloromethane at room temperature. The reaction proceeded for 24 hours, upon completion, quenched with brine, extracted with dichloromethane, and the organic layer was dried with sodium sulfate. The organic layer was filtered, concentrated in vacuo, and purified via column chromatography 100% hexanes to 3:1 hexanes:ethyl acetate to afford V55 (33.0 mg, 62%) as a brown residue.

(732) ##STR00226##

(733) Yield: 62%; 33.0 mg of V55 as brown residue. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 9.86 (s, 1H), 7.49 (d, J=7.9 1H), 7.44 (dt, J=8.1, 0.8 Hz, 1H), 7.22 (ddd, J=7.9, 7.1, 1.1 Hz, 1H), 7.11 (ddd, J=8.0, 7.1, 1.1 Hz, 1H), 4.31 (s, 1H), 3.77 (s, 3H), 3.70-3.54 (m, 2H), 3.23-3.11 (m, 2H), 3.04 (s, 3H), 3.03-2.91 (m, 2H), 2.42 (d, J=13.4 Hz, 1H), 2.32-2.19 (m 2H), 1.66-1.40 (m, 3H), 1.38-1.25 (m, 2H), 1.03 (t, J=7.4 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 174.6, 136.3, 133.3, 127.4, 122.7, 119.6, 118.2, 112.2, 111.8, 111.4, 81.1, 57.3, 53.6, 53.0, 51.9, 45.8, 38.1, 30.7, 26.8, 26.0, 23.7, 8.2. HRMS (ESI): calc. for C.sub.22H.sub.30N.sub.3O.sub.3 [M+H].sup.+: 384.2282, found: 384.2281.

(734) ##STR00227##

(735) Yield: 37%; 33.0 mg of V79 as a yellow-brown residue. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 10.08 (s, 1H), 7.80 (dd, J=8.2, 1.2 Hz, 1H), 7.52 (d, J=8.0 Hz, 1H), 7.49 (d, J=8.0 Hz, 1H), 7.29 (td, J=7.4, 1.0 Hz, 1H), 7.25-7.19 (m, 2H), 7.14 (ddd, J=7.9, 7.1, 0.9 Hz, 1H), 6.96 (td, J=7.6, 1.5 Hz, 1H), 4.54 (s, 1H), 4.24 (d, J=11.6 Hz, 1H), 4.13 (d, J=11.6 Hz, 1H), 3.79-3.67 (m, 1H), 3.53 (s, 3H), 3.26-3.09 (m, 2H), 2.96 (m, 1H), 2.49-2.36 (m, 2H), 2.32 (d, J=13.3 Hz, 1H), 1.65-1.48 (m, 2H), 1.47-1.40 (m, 2H), 1.39-1.24 (s, 2H), 1.00 (t, J=7.4 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) 174.7, 140.3, 139.6, 136.4, 132.9, 130.4, 129.7, 128.2, 127.4, 122.8, 119.7, 119.6, 118.4, 112.2, 111.9, 99.3, 78.8, 75.2, 53.6, 53.0, 51.8, 46.0, 38.3, 30.7, 26.9, 26.2, 23.7, 8.2. HRMS (ESI): calc. for C.sub.28H.sub.32IN.sub.3O.sub.3Na [M+Na].sup.+: 608.1381, found: 608.1405.

(736) ##STR00228##

(737) Yield: 37%; 33.0 mg of V7 as a yellow-brown residue. .sup.1H NMR: (400 MHz, CDCl.sub.3 at 50° C.) δ 9.83 (s, 1H), 7.48 (d, J=8.1 Hz, 1H), 7.42 (d, J=8.3 Hz, 1H), 7.21 (dd, J=7.3 Hz, 1H), 7.11 (ddd, J=8.1, 7.1, 1.0 Hz, 1H), 6.02 (ddd, J=17.4, 10.9, 6.0 Hz, 1H), 5.42 (dd, J=17.4, 1.3 Hz, 1H), 5.31 (d, J=10.4 Hz, 1H), 4.75-4.61 (m, 2H), 4.31 (s, 1H), 3.74-3.53 (m, 2H), 3.22-3.08 (m, 2H), 3.03 (s, 3H), 3.02-2.91 (m, 2H), 2.44 (d, J=13.4 Hz, 1H), 2.34-2.23 (m, 2H), 1.69-1.40 (m, 3H), 1.37-1.22 (m, 2H), 1.04 (t, J=7.4 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3 at 50° C.) δ 173.5, 136.3, 133.3, 132.5, 127.4, 122.7, 119.7, 119.6, 118.6, 118.3, 112.2, 111.8, 81.3, 65.8, 57.3, 53.6, 53.1, 45.9, 38.2, 30.7, 26.7, 26.0, 23.8, 8.2. HRMS (ESI): calc. for C.sub.24H.sub.31N.sub.3O.sub.3Na [M+Na].sup.+: 432.2258, found: 432.2261.

(738) ##STR00229##

(739) Procedure for the synthesis of V89: V58 (1.180 g, 3.61 mmol) was added to a round-bottom flask and dissolved in anhydrous dichloromethane (132.4 mL). The resulting solution was cooled to −41° C., and trifluoroacetic acid (5.0 mL, 61.5 mmol) was added and stirred for 5 minutes. m-Chloroperbenzoic acid (623.0 mg, 3.61 mmol) was added as a 0.3 M solution in anhydrous dichloromethane (12.0 mL). The reaction stirred for 12 hours at −41° C., upon completion, the reaction was quenched with 3 M aqueous ammonium hydroxide. Crude reaction was extracted with dichloromethane, washed with brine, and dried with sodium sulfate. Crude extract filtered, concentrated in vacuo, and purified via column chromatography using a gradient of 99:1 hexanes:triethylamine to 4.9:0.9:1.0 hexanes:ethyl acetate:triethylamine to afford V89 (294.3 mg, 34%) as a white-crystalline solid. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.49 (d, J=7.6 Hz, 1H), 7.41 (d, J=7.0 Hz, 1H), 7.31 (dd, J=8.2, 7.0 Hz, 1H), 7.18 (dd, J=8.2, 7.5 Hz, 1H), 4.48 (s, 1H), 3.55 (s, 3H), 3.12 (s, 1H), 3.06-2.97 (m, 2H), 2.88 (d, J=13.5 Hz, 1H), 2.62 (ddd, J=14.4, 9.8, 6.4 Hz, 1H), 2.39 (d, J=13.5 Hz, 1H), 2.27 (ddd, J=12.2, 7.8, 6.4 Hz, 1H), 2.10-1.95 (m, 3H), 1.92 (m, 1H), 1.74 (dq, J=14.6, 7.4 Hz, 1H), 1.63 (m, 1H), 1.60-1.42 (m, 2H), 1.05 (t, J=7.5 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 183.8, 173.6, 154.1, 139.9, 129.3, 126.2, 122.3, 121.0, 82.5, 71.5, 55.6, 51.5, 50.8, 40.7, 38.9, 32.2, 31.3, 29.7, 21.4, 8.1. HRMS (ESI): calc. for C.sub.20H.sub.27N.sub.2O.sub.3 [M+H].sup.+: 343.2046, found: 343.2036. MP: 122-124° C.

(740) TABLE-US-00003 TABLE 3 Crystal data and structure refinement for V#. Identification code chip4 Empirical formula C20H26N2O3 Formula weight 342.43 Temperature 100(2) K Wavelength 1.54178 Å Crystal system Orthorhombic Space group P2.sub.12.sub.12.sub.1 Unit cell dimensions a = 11.3809(3) Å α = 90°. b = 11.7902(3) Å β = 90°. c = 12.9504(4) Å γ = 90°. Volume 1737.72(8) Å.sup.3 Z 4 Density (calculated) 1.309 Mg/m.sup.3 Absorption coefficient 0.707 mm.sup.−1 F(000) 736 Crystal size 0.221 × 0.166 × 0.126 mm.sup.3 Theta range for data collection 5.073 to 66.480°. Index ranges −13 ≤ h ≤ 12, −13 ≤ k ≤ 14, −15 ≤ l ≤ 15 Reflections collected 14635 Independent reflections 3042 [R(int) = 0.0149] Completeness to theta = 66.480° 99.9% Absorption correction Empirical Max. and min. transmission 0.9398 and 0.8883 Refinement method Full-matrix least-squares on F.sup.2 Data/restraints/parameters 3042/0/231 Goodness-of-fit on F.sup.2 1.088 Final R indices [I > 2sigma(I)] R1 = 0.0254, wR2 = 0.0642 [3015] R indices (all data) R1 = 0.0256, wR2 = 0.0644 Absolute structure parameter 0.02(3) Largest diff. peak and hole 0.160 and −0.157 e .Math. Å.sup.−3

(741) ##STR00230##

(742) Procedure for the synthesis of V93: V52 (403.0 mg, 1.00 mmol) was added to a round-bottom flask and dissolved in a acetonitrile:water solution (2:1) (30.0 mL). The resulting solution was cooled to 0° C., and a 0.3 M solution of PIFA in acetonitrile was added slowly over 5 minutes. The reaction stirred for 3 hours at 0° C., upon completion, the reaction was quenched with cold saturated aqueous sodium bicarbonate. Crude reaction was extracted with dichloromethane, washed with brine, and the organic layer was dried with sodium sulfate. The organic layer was filtered, concentrated in vacuo, and purified via column chromatography using a gradient of 100% hexanes to 1:1 hexanes:ethyl acetate with 1% triethylamine throughout to afford V93 (108.7 mg, 26%) as a brown residue. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 7.48 (d, J=7.7 Hz, 1H), 7.40 (d, J=7.3 Hz, 1H), 7.31 (td, J=7.6, 1.3 Hz, 1H), 7.25-7.15 (m, 4H), 7.13-7.09 (m, 2H), 6.23 (t, J=5.6 Hz, 1H), 5.09 (s, 1H), 4.32 (dd, J=14.7, 5.6 Hz, 1H), 3.86 (dd, J=14.7, 5.6 Hz, 1H), 3.10 (s, 1H), 3.06-2.97 (m, 3H), 2.70-2.54 (m, 2H), 2.40 (d, J=13.7 Hz, 1H), 2.28 (ddd, J=12.2, 7.8, 2.2 Hz, 1H), 2.10-1.96 (m, 2H), 1.96-1.80 (m, 2H), 1.67-1.40 (m, 3H), 1.08 (t, J=7.4 Hz, 3H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 184.1, 171.9, 154.1, 139.9, 138.3, 129.3, 128.7, 128.0, 127.4, 126.2, 122.3, 121.0, 82.6, 72.0, 55.7, 50.9, 43.6, 41.0, 40.8, 32.9, 32.2, 29.9, 21.4, 8.3. HRMS (ESI): calc. for C.sub.26H.sub.32N.sub.3O.sub.2 [M+H].sup.+: 418.2489, found: 418.2484.

(743) ##STR00231##

(744) Procedure for the synthesis of V83: V89 (12.9 mg, 0.038 mmol) was added to a round-bottom flask and dissolved in methanol (1.5 mL). Sodium hydroxide (8.0 mg, 0.19 mmol) was added and the reaction was heated to 64° C. after being equipped with a reflux condenser. The reaction was quenched with brine, extracted with chloroform, and the organic layer was dried with sodium sulfate. The organic layer was filtered, concentrated in vacuo, and purified via column chromatography 100% hexanes to 3:1 hexanes:ethyl acetate with 1% triethylamine throughout to afford V83 (9.7 mg, 82%) as a white-brown solid. .sup.1H NMR: (400 MHz, CDCl.sub.3) δ 8.29 (d, J=8.2 Hz, 1H), 7.75 (d, J=7.7 Hz, 1H), 7.66 (td, J=7.8, 1.4 Hz, 1H), 7.24 (dd, J=7.8, 7.5 Hz, 1H), 3.44 (d, J=15.6 Hz, 1H), 3.11 (m, 1H), 3.03 (dd, J=8.8, 7.4 Hz, 1H), 2.53 (s, 1H), 2.49 (m, 1H), 2.30 (td, J=11.4, 3.1 Hz, 1H), 2.17 (dd, J=12.4, 5.5 Hz, 1H), 2.11 (dd, J=15.6, 2.1 Hz, 1H), 1.95 (td, J=11.3, 7.8 Hz, 1H), 1.79-1.67 (m, 2H), 1.61 (m, 1H), 1.21 (m, 1H), 0.91 (m, 1H), 0.78-0.69 (m, 4H). .sup.13C NMR: (100 MHz, CDCl.sub.3) δ 200.9, 170.9, 152.3, 136.9, 125.0, 124.5, 122.7, 119.9, 75.5, 68.8, 51.6, 51.0, 40.9, 38.4, 38.3, 32.3, 30.1, 22.3, 7.1. HRMS (ESI): calc. for C.sub.19H.sub.23N.sub.2O.sub.2 [M+H].sup.+: 311.1754, found: 311.1756. MP: 115-117° C.

Example 2. Biological Assays

(745) Biological Methods

(746) ARE Luciferase Assay in LNCaP and MDA-MB-231-ARE-Luc Cells

(747) The antioxidant response element (ARE) expression induction assay with LNCaP cells was performed as previously described..sup.10 The ARE expression inhibition assay was performed with MDA-MB-231-ARE-Luc cells that stably express the ARE reporter construct..sup.11 MDA-MB-231-ARE-Luc cells were seeded in 96 well plates at 1.5×10.sup.4 cells/well in DMEM medium (GIBCO) containing 10% FCS and 1% antibiotic-antimycotic (GIBCO), and allowed to attach overnight. Test compounds were screened in triplicate at three concentrations (100, 10 and 1 μM) and ARE expression was quantified on the EnVision plate reader (Perkin-Elmer) using the BriteLite plus luciferase reporter assay system (Perkin-Elmer) after 24 h exposure in a humidified incubator at 37° C. with 5% CO.sub.2. In both cell line assays the luciferase expression for compound-treated wells was expressed relative the 0.5% DMSO carrier solvent control. A parallel viability assay was performed with the Cell Titer 96 Non-radioactive Cell Proliferation Assay (Promega) and the data expressed in the same manner as above. Compounds that inhibited ARE expression 20% more than viability, or induced ARE expression more than three-fold were re-tested in a seven-point, two-fold serial dilution dose-response assay (100-1.56 μM). Compounds that displayed activity comparable to the primary screen were assessed for their effect on the expression of Ngo1 by RT-qPCR.

(748) RT-qPCR Validation

(749) In order to validate the ARE modulatory effects of compounds from the primary screen, the expression of the target Nrf2 target gene, Nqo1, was quantified by RT-PCR. LNCaP and MDA-MB-231-ARE-Luc cells were seeded in 6 well plates at 5×10.sup.5 and 7×10.sup.5 cells per well, in EMEM and DMEM media containing 10% FCS and 1% antibiotic-antimycotic (GIBCO) respectively. Cells were allowed to attach overnight before the addition of test compounds. After 24 h exposure in a humidified incubator at 37° C. with 5% CO.sub.2, RNA was isolated using the RNeasy kit (Qiagen) and quantified using a NanoDrop spectrophotometer (Thermo Fisher Scientific). cDNA was synthesized from 2 μg of RNA using Oligo(dT)12-18 (Life Technologies) primer and SuperScript II (Thermo Fisher Scientific) on the Mastercycler Gradient PCR machine (Eppendorf) for 1 h at 42° C. following a 10 min denaturation at 65° C. Gene expression was quantified on the 7300 Real Time PCR machine (Applied Biosystems) using TaqMan Gene Expression Master Mix (Thermo Fisher Scientific) and probes for the target gene Nqo1 (Hs02512143_s1, Thermo Fisher Scientific) and reference gene ActB (Hs99999903_ml, Thermo Fisher Scientific). Real time PCR was performed with the following thermal cycle: 1. 50° C. for 2 min; 2. 95° C. for 10 min; 3. 40 cycles of 95° C. for 15 sec followed by 60° C. for 1 min.

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