DIMERS FROM BIOREACHABLE MOLECULES AS COPOLYMERS

Abstract

The present disclosure relates to compositions derived from bioreachable molecules, such as amino acids or hydroxy acids. In particular, the composition can be a monomer, a polymer, or a copolymer derived from an amino acid dimer or a hydroxy acid dimer.

Claims

1. A composition comprising a structure having formula (I) or (II): ##STR00068## or a salt thereof, wherein: each of G.sup.1 and G.sup.2 comprises, independently, hydroxyl, carboxyl, amino, amido, cyanato, isocyanato, cyano, isocyano, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted (hetero)cycloalkyl, or optionally substituted epoxy; each of R.sup.1 and R.sup.2 is, independently, H or optionally substituted alkyl; X.sup.1 is oxy or —N—R.sup.g1, wherein R.sup.g1 is H, optionally substituted alkyl, optionally substituted aryl, or optionally substituted aralkyl; X.sup.2 is oxy or —N—R.sup.g2, wherein R.sup.g2 is H, optionally substituted alkyl, optionally substituted aryl, or optionally substituted aralkyl; R.sup.g1 and G.sup.1, taken together with the nitrogen to which R.sup.g1 is bound, can optionally form an optionally substituted heterocyclyl; and R.sup.g2 and G.sup.2, taken together with the nitrogen to which R.sup.g2 is bound, can optionally form an optionally substituted heterocyclyl.

2. The composition of claim 1, wherein: G.sup.1 is -L.sup.G1-L.sup.G3-R.sup.G1, -L.sup.G1-Ar.sup.G1—R.sup.G1, -L.sup.G1-Het.sup.G1-R.sup.G1, or -L.sup.G1-Ar.sup.G1-L.sup.G3-R.sup.G1; G.sup.2 is -L.sup.G2-L.sup.G4-R.sup.G2, -L.sup.G2-Ar.sup.G2—R.sup.G2, -L.sup.G2-Het.sup.G2-R.sup.G2, or -L.sup.G2-Ar.sup.G1-L.sup.G4-R.sup.G2; each of L.sup.G1 and L.sup.G2 is, independently, a covalent bond, an amide bond, oxy, optionally substituted alkylene, optionally substituted alkenylene, optionally substituted heteroalkylene, optionally substituted arylene, optionally substituted (aryl)(alkyl)ene, optionally substituted heterocyclyldiyl, or optionally substituted (heterocyclyl)(alkyl)ene; each of Ar.sup.G1 and Ar.sup.G2 is, independently, optionally substituted arylene or optionally substituted (aryl)(alkyl)ene; each of Het.sup.G1 and Het.sup.G2 is, independently, optionally substituted heterocyclyldiyl or optionally substituted (heterocyclyl)(alkyl)ene; each of L.sup.G3 and L.sup.G4 is, independently, a covalent bond, —NR.sup.N1—, or oxy, wherein R.sup.N1 is H or optionally substituted alkyl; and each of R.sup.G1 and R.sup.G2 is, independently, hydroxyl, carboxyl, amino, amido, cyanato, isocyanato, cyano, isocyano, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted (hetero)cycloalkyl, or optionally substituted epoxy.

3. The composition of claim 2, wherein the optionally substituted alkenyl has a structure of: ##STR00069## wherein each of R.sup.a, R.sup.b, and R.sup.c is, independently, H, optionally substituted alkyl, or optionally substituted alkenyl; and wherein a1 is an integer of from 0 to 4.

4. The composition of claim 2, wherein the optionally substituted epoxy has a structure of: ##STR00070## wherein each of R.sup.a, R.sup.b, and R.sup.c is, independently, H, optionally substituted alkyl, or optionally substituted alkenyl; and wherein a1 is an integer of from 0 to 4.

5. The composition of claim 1, wherein the composition comprises a structure having formula (Ia): ##STR00071## or a salt thereof, wherein: each of R.sup.g1 and R.sup.g2 is, independently, H, optionally substituted alkyl, optionally substituted aryl, or optionally substituted aralkyl; R.sup.g1 and G.sup.1, taken together with the nitrogen to which R.sup.g1 is bound, can optionally form an optionally substituted heterocyclyl; and R.sup.g2 and G.sup.2, taken together with the nitrogen to which R.sup.g2 is bound, can optionally form an optionally substituted heterocyclyl.

6. The composition of claim 1, wherein the composition comprises a structure having formula (Ib): ##STR00072## or a salt thereof.

7. The composition of claim 1, wherein the composition comprises a structure having formula (Ic): ##STR00073## or a salt thereof.

8. The composition of claim 1, wherein the composition comprises a structure having formula (Id): ##STR00074## or a salt thereof, wherein: each of L.sup.G1 and L.sup.G2 is, independently, a covalent bond, an amide bond, —NR.sup.N1—, oxy, optionally substituted alkylene, optionally substituted alkenylene, optionally substituted heteroalkylene, optionally substituted arylene, optionally substituted heterocyclyldiyl, or optionally substituted (heterocyclyl)(alkyl)ene; and each of R.sup.G1 and R.sup.G2 is, independently, hydroxyl, optionally substituted hydroxyalkyl, optionally substituted hydroxyaryl, carboxyl, amino, optionally substituted aminoalkyl, optionally substituted aminoaryl, amido, cyanato, isocyanato, cyano, isocyano, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted (hetero)cycloalkyl, or optionally substituted epoxy.

9. The composition of claim 1, wherein the composition comprises a structure selected from the group consisting of: ##STR00075## or a salt thereof.

10. The composition of claim 1, wherein the composition comprises a structure selected from the group consisting of: ##STR00076## ##STR00077## or a salt thereof.

11. The composition of claim 1, wherein the composition comprises a structure selected from the group consisting of: ##STR00078## ##STR00079## or a salt thereof.

12. The composition of claim 1, wherein the composition is a monomer, a polymer, or a copolymer.

13. A method of making a composition of claim 1, the method comprising: providing a first amino acid and a second amino acid, wherein the first and second amino acids are selected from the group consisting of hydroxymandelic acid, hydroxyproline, serine, and tyrosine; and forming a dimer between the first and second amino acids.

14. The method of claim 13, thereby producing a monomer for a copolymer.

15. A method of making a composition of claim 1, the method comprising: providing a first amino acid and a second amino acid, wherein the first and second amino acids are selected from the group consisting of tyrosine, tryptophan, phenylalanine, vinylglycine, allylglycine, and a derivative thereof comprising an optionally substituted alkenyl; and forming a dimer between the first and second amino acids; and optionally epoxidizing the dimer in the presence of an oxidant.

16. The method of claim 15, wherein the first and second amino acids are selected from the group consisting of L-vinylglycine, L-allylglycine, O-allyl-L-tyrosine, O-buten-3-enyl-L-tryrosine, O-(3-methyl-but-2-enyl)-L-tryrosine, O-(4-methyl-pent-3-enyl)-L-tryrosine, 4-allyl-L-phenylalanine, 4-but-3-enyl-L-phenylalanine, 6-allyl-L-tryptophan, and 6-(3-methylbut-2-enyl)-L-tryptophan, or a salt thereof.

17. The method of claim 15, thereby producing an ion-free epoxy resin.

18. The method of claim 17, wherein the total ion content is less than 1 part per thousand.

19. A method of making a composition of claim 1, the method comprising: providing an organism a plurality of amino acids, thereby producing a plurality of prenylated amino acids; and forming a dimer between two of the plurality of amino acids.

20. A film comprising a composition of claim 1.

21. The film of claim 20, wherein the film is an adhesive or a coating.

22. A composite or bulk structure comprising a composition of claim 1.

23. A fiber or a particle comprising a composition of claim 1.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0076] FIG. 1 shows a schematic of illustrative cyclic derivatives formed from bioreachable molecules.

[0077] FIG. 2 shows an illustrative schematic of modifying a bioreachable molecule to provide biorthogonal reaction chemistry.

DETAILED DESCRIPTION

[0078] The present disclosure relates to compositions derived from bioreachable molecules, such as amino acids or hydroxy acids obtained from microbes (e.g., engineered microbes to overexpress desired biomolecules). Such bioreachable molecules can be reacted to form a cyclic dimer, which can be further chemically functionalized to provide a cyclic derivative. Such functionalization can include, e.g., inclusion of one or more reactive moieties, polymerizable moieties, or others. In turn, such cyclic derivatives can be employed as a monomer, a polymer, or a copolymer.

[0079] In one aspect, the cyclic derivative can include a structure having formula (I), (Ia), (Ib), or (Ic):

##STR00011##

or a salt thereof. In some embodiments, each of G.sup.1 and G.sup.2 is or includes, independently, hydroxyl, carboxyl, amino, amido, cyanato, isocyanato, cyano, isocyano, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted (hetero)cycloalkyl, or optionally substituted epoxy. In some embodiments, each of R.sup.1 and R.sup.2 is, independently, H or optionally substituted alkyl. In other embodiments, X.sup.1 is oxy or —N—R.sup.g1, and X.sup.2 is oxy or —N—R.sup.g2. In yet other embodiments, each of R.sup.g1 and R.sup.g2 is, independently, H, optionally substituted alkyl, optionally substituted aryl, or optionally substituted aralkyl. In particular embodiments, R.sup.g1 and G.sup.1, taken together with the nitrogen to which R.sup.g1 is bound, and/or R.sup.g2 and G.sup.2, taken together with the nitrogen to which R.sup.g2 is bound, can optionally form an optionally substituted heterocyclyl.

[0080] In another aspect, the cyclic derivative can include a structure having formula (II):

##STR00012##

or a salt thereof, wherein each of G.sup.1 and G.sup.2 comprises, independently, hydroxyl, carboxyl, amino, amido, cyanato, isocyanato, cyano, isocyano, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted (hetero)cycloalkyl, or optionally substituted epoxy.

[0081] As can be seen, in some instances, G.sup.1 and G.sup.2 include one or more reactive moieties, which in turn can provide a polymer when the cyclic derivative is employed as a monomer. Within a polymer, the same cyclic derivative can be employed, or two or more different cyclic derivatives may be employed. Illustrative reactive moieties include, e.g., those described herein for R.sup.G, R.sup.G1, or R.sup.G2, such as hydroxyl, halo, haloalkyl, carboxyl, amino, amido, cyanato, isocyanato, cyano, isocyano, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted (hetero)cycloalkyl (e.g., optionally substituted oxiranyl or optionally substituted oxetanyl), or optionally substituted epoxy.

[0082] In some embodiments, each of G.sup.1 and G.sup.2 has a structure of:

##STR00013##

in which each of R.sup.1, R.sup.2, and R.sup.3 is, independently, H, optionally substituted alkyl, or optionally substituted alkenyl; Ar is optionally substituted arylene, such as divalent forms of benzene, naphthalene, biphenyl, phenoxy, aniline, etc. (boiler plate here would be great); Het is optionally substituted heterocyclyldiyl, such as divalent forms of indole, benzofuran, thianaphthene, imidazole, furan, thiophene; and each of G.sup.3 and G.sup.4 can be optionally substituted alkenyl (e.g., vinyl, allyl, homoallyl, olefin, and combinations thereof, as well as any described herein). In the foregoing structure, n can be an integer selected from 1 through 5.

[0083] In yet other embodiments, each of G.sup.1 and G.sup.2 has a structure of:

##STR00014##

OH, or -G.sup.3OH, in which G.sup.3 can be optionally substituted alkylene, optionally substituted arylene, or optionally substituted (aryl)(alkyl)ene. In one embodiment, G.sup.3 can be methylene, ethylene, n-propylene, isopropylene, n-butylene, 2-methylpropylene, n-pentylene, 2-methylbutylene, 2,3-dimethylpropylene, 1,4-phenylene, methylene-phenylene, para-methylene-phenylene, ethylene-phenylene, or para-ethylene-phenylene.

[0084] In some embodiments, each of G.sup.1 and G.sup.2 can include one or more linkers (e.g., L.sup.G1, L.sup.G2, L.sup.G3, L.sup.G4, Ar.sup.G1, Ar.sup.G2, Het.sup.G1, or Het.sup.G2) attached to a reactive moiety (e.g., R.sup.G, R.sup.G1, or R.sup.G2). Illustrative linkers include, e.g., a covalent bond, an amide bond, —NR.sup.N1— (in which R.sup.N1 is H or optionally substituted alkyl), oxy, optionally substituted alkylene, optionally substituted alkenylene, optionally substituted heteroalkylene, optionally substituted arylene, optionally substituted (aryl)(alkyl)ene, optionally substituted heterocyclyldiyl, or optionally substituted (heterocyclyl)(alkyl)ene, as well as combinations thereof. Yet other linkers can include -L.sup.G1-L.sup.G3-, -L.sup.G1-Ar.sup.G1—, -L.sup.G1-Het.sup.G1-, -L.sup.G1-Ar.sup.G1-L.sup.G3-, -L.sup.G2-L.sup.G4-, -L.sup.G2-Ar.sup.G2—, -L.sup.G2-Het.sup.G2-, or -L.sup.G2-Ar.sup.G2-L.sup.G4-, for any L.sup.G1, L.sup.G2, L.sup.G3, L.sup.G4, Ar.sup.G1, Ar.sup.G2, Het.sup.G1, or Het.sup.G2 described herein.

[0085] In particular embodiments, the cyclic derivative can include a structure having formula (Id):

##STR00015##

or a salt thereof, in which X.sup.1 and X.sup.2 can be any described herein; L.sup.G1 and L.sup.G2 can be any linker described herein; and R.sup.G1 and R.sup.G2 can be any reactive moiety described herein.

[0086] Such linkers and reactive moieties may be attached to a side chain present in the amino acid or hydroxy acid employed to form the cyclic dimer. Exemplary side chains can include, e.g., alkyl, amidoalkyl, aminoalkyl, carboxyalkyl, hydroxyalkyl, phenyl, aryl, aralkyl, hydroxyphenyl, hydroxyaryl, hydroxyaralkyl, or heterocyclyl. Accordingly, each of G.sup.1 and G.sup.2 can include any of such side chains that has been reacted to provide a linker (e.g., L.sup.G1, LG.sup.2, L.sup.G3, L.sup.G4, Ar.sup.G1, Ar.sup.G2, Het.sup.G1, or Het.sup.G2) attached to a reactive moiety (e.g., R.sup.G, R.sup.G1, or R.sup.G2).

[0087] In other embodiments, the cyclic derivative can include a structure having formula (Ie), (If), or (Ig):

##STR00016##

or a salt thereof, in which R.sup.g1 and R.sup.g2 can be any described herein; L.sup.G1, L.sup.G2, L.sup.G3, and L.sup.G4 can be any linker described herein; and R.sup.G1 and R.sup.G2 can be any reactive moiety described herein.

[0088] In yet other embodiments, the cyclic derivative can include a structure having formula (Ih), (Ii), or (Ij):

##STR00017##

or a salt thereof, in which L.sup.G1, L.sup.G2, L.sup.G3, and L.sup.G4 can be any linker described herein; and R.sup.G1 and R.sup.G2 can be any reactive moiety described herein.

[0089] In some embodiments (e.g., in formula (Ie), (If), (Ig), (Ih), (Ii), (Ij), or any herein), each of L.sup.G1, L.sup.G2, L.sup.G3, and L.sup.G4 is, independently, a covalent bond, oxy, optionally substituted alkylene, or optionally substituted heteroalkylene. In particular embodiments, the optionally substituted heteroalkylene is —O-Ak- or -Ak-O—, in which Ak is an optionally substituted alkylene (e.g., C.sub.1-3 alkylene). In other embodiments, each of R.sup.G1 and R.sup.G2 is, independently, optionally substituted alkylene (e.g., vinyl, allyl, optionally substituted butenyl, optionally substituted pentenyl, and the like), optionally substituted (hetero)cycloalkyl (e.g., optionally substituted epoxy, optionally substituted oxiranyl, optionally substituted oxetanyl, and the like).

[0090] In one embodiment, the reactive moiety is or includes an optionally substituted alkenyl or an optionally substituted epoxy. Thus, G.sup.1, G.sup.2, R.sup.G, R.sup.G1, or R.sup.G2 can include such a reactive moiety. In some embodiments, the optionally substituted alkenyl has a structure of:

##STR00018##

In other embodiments, the optionally substituted epoxy has a structure of:

##STR00019##

In each of these structures, each of R.sup.a, R.sup.b, and R.sup.c is, independently, H, optionally substituted alkyl, or optionally substituted alkenyl; and a1 is an integer of from 0 to 4.

[0091] In another embodiment, the reactive moiety is or includes hydroxyl, optionally substituted hydroxyalkyl, or optionally substituted hydroxyaryl. In particular embodiments, the cyclic derivative can include a structure selected from the group of:

##STR00020##

or a salt thereof, in which R.sup.g1 and R.sup.g2 can be any described herein.

[0092] Reactive moieties can also be characterized as a polymerizable group. A polymerizable group includes groups that form homopolymers or copolymers. In a first embodiment, the polymerizable group can form predominately homopolymers, meaning that the compound A forms polymers symbolized as -(A-A-A).sub.x-, wherein x is an integer. These groups are defined as homopolymerizable. Examples of such groups are unsaturated groups, such as vinyl and allyl groups, oxiranes (ethylene oxides or epoxides), aziridines (ethylene imines), oxetanes. In another embodiment, the polymerizable group is copolymerizable, i.e., a second compound B is required to form polymers -(A-B-A-B).sub.x-, wherein x is an integer. Examples of such groups are carboxylic acids, hydroxyl groups, amino groups, thiol groups; and examples for the respective copolymer monomer would be diols or diamines, diacids, diacid anhydrides, isocyanates, di-isocyanates.

[0093] In one embodiment, the polymerizable group can be selected from a vinyl group, an allyl group, an epoxy group, or a combination thereof.

[0094] In another embodiment, at least 35 wt. %, such as at least 40 wt. %, at least 45 wt. %, at least 50 wt. %, at least 55 wt. %, at least 60 wt. %, at least 65 wt. %, at least 70 wt. %, at least 75 wt. %, at least 80 wt. %, or at least 85 wt. % of the compound or the composition is comprised by the moiety. In another embodiment, not more than 98 wt. %, such as not more than 96 wt. %, not more than 95 wt. %, not more than 94 wt. %, not more than 92 wt. %, or not more than 90 wt. % of the compound or the composition are comprised by the moiety. In yet one further embodiment, the moiety of the compound or the composition has weight percentage in the range between 30 wt. % to 99.5 wt. %, such as 40 wt. % to 98 wt. %, or even 50.5 wt. % to 96 wt. %.

[0095] In yet one further embodiment, at least 60 wt. %, at least 65 wt. %, at least 70 wt. %, at least 75 wt. %, at least 80 wt. %, at least 85 wt. %, or at least 88 wt. % of the compound or the composition are comprised by the sum of weight percentages of the moiety and the polymerizable group. In another embodiment, not more than 99.9 wt. %, such as not more than 99 wt. %, not more than 98 wt. %, not more than 96 wt. %, not more than 94 wt. %, not more than 92 wt. %, not more than 90 wt. %, not more than 85 wt. %, or not more than 80 wt. % of the compound or the composition are comprised by the sum of weight percentages of the moiety and the polymerizable group. In yet one further embodiment, the sum of weight percentages of the moiety and the polymerizable group can range between 55 wt. % to 99.99 wt. %, such as 65 wt. % to 99 wt. %, or 75 wt. % to 98 wt. %.

[0096] In any of the formulas herein, R.sup.g1 and R.sup.g2 can be H, optionally substituted alkyl, haloalkyl, alkoxyalkyl, or any combination thereof. Other non-limiting R.sup.g1 and R.sup.g2 groups include, independently for each occasion, hydrogen or C.sub.1-20 straight or branched alkyl chains, such as methyl, ethyl, n-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methylpropyl, pentyl, 2-methylbutyl, 2,2-dimethylpropyl, hexyl, 2-methylpentyl, 3-methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, heptyl, 2-methylhexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, 2,4-dimethylpentyl, 3,3-dimethylpentyl, 3-ethylpentyl, 2,2,3-trimethylbutyl, octyl, 2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 5-methylheptyl, 6-methylheptyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 3,4-dimethylhexyl, 3,5-dimethylhexyl, 4,5-dimethylhexyl, 2-propylpentyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, and icosyl.

[0097] In a further embodiment, the foregoing compound or composition has a bio-based carbon content of at least 10%, such as at least 15%, at least 20%, at least 25%, at least 30%, or at least 35% as determined by ASTM D6866. Bio-based carbon content as defined herein is the percentage of carbons from renewable or biogenic sources, such as plants or animals over the total number of carbons in the compound.

[0098] For example, the following cyclic derivative is prepared from bio-sourced tyrosine and petro chemically epichlorohydrin:

##STR00021##

Then, 16 carbon atoms are bio-based and 6 carbon atoms are petrochemically sourced. Upon analysis according to ASTM D6866, this compound has a bio-based carbon content of 16/(16+6)=72.7%.

[0099] Additional cyclic dimers and cyclic derivatives are provided below in Table 1.

TABLE-US-00001 TABLE 1 Non-limiting cyclic dimers and cyclic derivatives Compound No. Structure I-1  [00022] I-2  [00023] I-3  [00024] I-4  [00025] I-5  [00026] I-6  [00027] I-7  [00028] I-8  [00029] I-9  [00030] I-10 [00031] I-11 [00032] I-12 [00033] I-13 [00034] I-14 [00035] I-15 [00036] I-16 [00037] I-17 [00038] I-18 [00039] I-19 [00040] I-20 [00041] I-21 [00042] I-22 [00043] I-23 [00044] I-24 [00045] I-25 [00046] I-26 [00047] I-27 [00048] I-28 [00049] I-29 [00050] I-30 [00051]

[0100] The cyclic derivatives herein can be prepared in any useful manner, such as by providing a first biomolecule and a second biomolecule and forming a dimer between the first and second biomolecules. The first and second biomolecules can be any herein, including, e.g., amino acids, hydroxy acids, hydroxymandelic acid, hydroxyproline, serine, tyrosine, tryptophan, phenylalanine, vinylglycine, allylglycine, and derivatives of any of these including an optionally substituted alkenyl. Additional non-limiting biomolecules are further described herein. The dimer can be further functionalized (e.g., to include one or more linkers and/or reactive moieties). The methods herein can further include epoxidizing the dimer in the presence of an oxidant (e.g., chlorine, hypochlorous acid, a peroxycarboxylic acid, a peroxycarboxylate, a peroxyphthalate, or a combination thereof).

[0101] In other embodiments, the cyclic derivates are prepared by providing an organism with a plurality of amino acids, thereby producing a plurality of prenylated amino acids; and then forming a dimer between two of the plurality of amino acids. The plurality of amino acids can be any herein, including, e.g., glycine, serine, tyrosine, tryptophan, phenylalanine, and the like. Additional amino acids are described herein.

[0102] In yet other embodiments, the cyclic derivatives herein can be prepared by processes analogous to those established in the art, for example, by the reaction sequences shown in Schemes 1-3.

##STR00052##

[0103] As seen in Scheme 1, amino acids (1a, 1b) can be provided, in which R.sup.1 and R.sup.2 can be H, alkyl, any described herein for R.sup.1 and R.sup.2; and in which A.sup.1 and A.sup.2 can be an amino acid side chain or a functionalized form thereof. Substituents within the amino acid can be optionally protected with a protecting group (e.g., an N-protecting group for amino or an O-protecting group for hydroxyl) or can be optionally functionalized to provide a better leaving group (e.g., an alkylating agent for oxygen to provide an alkoxy leaving group). Amino acids (1a, 1b) can be the same or different. Furthermore, such amino acids can be optionally provided by a biological resource.

[0104] Cyclic amino acids (2) can be provided by dimerization and cyclization of the amino acids (1a, 1b) in the presence of a solvent (e.g., ethylene glycol). If desired, dimers can first be formed to promote internal cyclization within the dimer. Dimerization can be performed in any useful manner (e.g., with use of protecting groups); and subsequent cyclization can optionally be performed under catalytic conditions (e.g., with subsequent deprotection chemistry to remove protecting groups).

[0105] Reactive moieties can then be provided. Cyclic amino acid (2) can be functionalized with R.sup.G-LG to provide a cyclic derivative (3), in which R.sup.G is or includes a reactive moiety (e.g., any described herein, such as for R.sup.G, R.sup.G1, or R.sup.G2) and LG is a leaving group (e.g., halo).

[0106] Further functionalization of compound (3) can provide another cyclic derivative (4), in which nitrogen atoms of the diketopiperazine can include be further substituted. Here, compound (3) can be functionalized with R.sup.g-LG to provide cyclic derivative (4), in which R.sup.g can be any described herein (e.g., such as for R.sup.g1 and R.sup.g2).

##STR00053##

[0107] As seen in Scheme 2, proline derivatives (5a, 5b) can be provided, in which A.sup.1 and A.sup.2 can be an amino acid side chain or a functionalized form thereof. In one instance, A.sup.1 and A.sup.2 includes hydroxyl for a hydroxyproline derivative (e.g., 4-hydroxyproline). Amino acids (5a, 5b) can be the same or different and can be optionally provided by a biological resource.

[0108] Cyclic amino acids (6) can be provided by dimerization and cyclization of the amino acids (5a, 5b) in the presence of a solvent (e.g., ethylene glycol). Reactive moieties can then be provided by functionalizing the cyclic amino acid (6) with R.sup.G-LG to provide a cyclic derivative (7), in which R.sup.G is or includes a reactive moiety (e.g., any described herein, such as for R.sup.G, R.sup.G1, or R.sup.G2) and LG is a leaving group (e.g., halo).

##STR00054##

[0109] Hydroxy acids can also be employed to form cyclic derivatives. As seen in Scheme 3, hydroxy acids (8a, 8b) can be provided, in which R.sup.1 and R.sup.2 can be H or alkyl; and in which A.sup.1 and A.sup.2 can be alkyl, aryl, aralkyl, or a substituted form thereof. Substituents within the hydroxy acid can be optionally protected with a protecting group (e.g., an O-protecting group for hydroxyl) or can be optionally functionalized to provide a better leaving group (e.g., an alkylating agent for oxygen to provide an alkoxy leaving group). Hydroxy acids (8a, 8b) can be the same or different and can be optionally provided by a biological resource.

[0110] Cyclic hydroxy acids (9) can be provided by dimerization and cyclization of the hydroxy acids (8a, 8b) in the presence of a solvent, and further functionalization can include use of R.sup.G-LG to provide a cyclic derivative (10), in which R.sup.G is or includes a reactive moiety (e.g., any described herein, such as for R.sup.G, GR or R.sup.G2) and LG is a leaving group (e.g., halo).

[0111] Methods herein also include those for preparing a resin, which can include reacting a cyclic dimer or a cyclic derivative with a reagent. The cyclic dimer or cyclic derivative can include, e.g., OH groups. Furthermore, reacting can include initiation at a ratio of moles of OH groups per moles of reagent ranging from 10:1 to 1:1. Non-limiting reagents include, e.g., epichlorohydrin, epibromohydrin, allyl halides, vinyl halides, unsaturated acids, allyl halides, vinyl halides, unsaturated acids, or any combination thereof.

[0112] In some instances, providing a reactive moiety by way of the reagent can further result in polymerization of cyclic derivatives. For instance, as shown below:

##STR00055##

wherein X can be a leaving group (e.g., halo, such as Cl or Br).

[0113] Methods of preparing a resin can further include adding an oxidant. In this instance, the cyclic dimer or cyclic derivative can be reacted with a reagent to provide a reactive group (e.g., a polymerizable group) that can be further treated with an oxidant, such as by an epoxidation reaction:

##STR00056##

wherein X is a leaving group (e.g., halo, such as Cl or Br), [O] is an oxidant, and n is an integer including zero. The epoxidation reaction can be stoichiometric, i.e., one mole of epichlorohydrin or epibromohydrin per mole of hydroxy groups in the moiety. Alternatively, epoxidation can be conducted to a lesser degree, wherein the ratio of moles of hydroxy group over moles of reagent can range from 20:1 to 0.9:1, such as from 15:1 to 1:1, 10:1 to 1:1, or 5:1 to 1:1. This is true for any other reagent that renders the moiety polymerizable, such as allyl halides or vinyl halides.

[0114] The oxidation reaction in the above scheme serves to render epoxides from unsaturated organic groups. In one embodiment, an oxidation reaction is omitted to allow the unsaturated group to be the polymerizable group. Here too, all hydroxyl groups or a fraction thereof can react to give a polymerizable group. Oxidants can be peroxides, percarboxylic acids, percarboxylic esters, peroxycarboxylates, peroxyphthalates, percarboxylic salts, chlorine, hypochlorous acid, hypochlorites, or combinations thereof. In epoxidized dimers, the epoxy groups can be symmetrically located in ortho, meta, or para positions, but also asymmetrical locations, i.e., ortho-meta, ortho-para, or meta-para are contemplated within this disclosure.

Biomolecules, Including Amino Acids, Hydroxy Acids, and Derivatives Thereof

[0115] As described herein, the compositions and methods herein can employ biomolecules, which can be further undergo dimerization, cyclization, and/or functionalization. Non-limiting biomolecules include amino acids and hydroxy acids (e.g., alpha hydroxy acids), such as glycine, vinylglycine, allylglycine, alkenylglycine, tyrosine, O-allyltyrosine, O-alkenyltryrosine, tryptophan, allyltryptophan, alkenyltryptophan, phenylalanine, allylphenylalanine, alkenylphenylalanine, hydroxymandelic acid (e.g., 4-hydroxymandelic acid, 3-hydroxymandelic acid, DL-4-hydroxy-3-methoxymandelic acid, DL-3,4-dihydroxymandelic acid, and others), hydroxyproline (e.g., 4-hydroxyproline), or serine.

[0116] Yet other non-limiting biomolecules can include, e.g., derivatives of any amino acids or hydroxy acids including an alkenyl, alkenyloxy (e.g., —O-Ak, in which Ak is alkenyl), carboxyl, or hydroxyl moiety. In particular embodiments, the biomolecule is an L-amino acid or a functionalized L-amino acid having an alkenyl, alkenyloxy (e.g., —O-Ak, in which Ak is alkenyl), carboxyl, or hydroxyl moiety.

[0117] Other non-limiting biomolecules also include the following:

##STR00057##

as well as salts thereof and stereoisomers thereof.

[0118] Biomolecules can be formed in any useful manner. In one instance, the biomolecules are produced from yeast, gram positive bacteria, gram negative bacteria, or fungi. In other embodiments, amino acids, as well as derivatives thereof and/or dimers thereof, are produced biologically by way of fermentation and/or prenylation. In particular embodiments, prenylation may involve feeding the organism the starting amino acid. In yet other embodiments, amino acid dimers are produced by chemical means using petro-based starting materials.

Applications

[0119] The compositions herein can be employed as ingredients and/or monomers in any useful application. Exemplary, non-limiting applications include adhesives, coatings, films, and plastics. Such applications can include materials for use in constructing electronics, industrial adhesives, architectural adhesives and coatings, civil engineering adhesives and coatings, transportation adhesives and coatings, handheld devices, electronic devices, energy storage devices, energy generation devices, personal electronics (e.g., smart phones, laptops, or tablets), displays, sensors, semi-conductor materials (e.g., such as in chip patterning, manufacturing, and packaging), packages, and the like.

[0120] Yet other applications include use of the composition as a polymer curative, a resin (e.g., an ion free resin), a monomer for a polymer or a copolymer, and the like. The composition can be provided in any useful form, such as a film, a composite structure, a bulk structure, a fiber, or a particle. The composition can optionally include one or more hardeners for use with the cyclic derivatives. Non-limiting hardeners include, e.g., diamines (such as 1,4-diamino butane (DAB) or 1,13-diamino-4,7,10-trioxatridecane (TDD). If desired, the composition can also include an accelerator, such as tris(dimethylaminomethyl)phenol, or other additives (e.g., resorcinol diglycidyl ether).

[0121] In particular embodiments, the compositions herein can undergo bio-triggered degradation for debonding of adhesives, coatings, and composites. Degradation can be triggered, e.g., by employing one or more proteases, hydrolases, and the like.

[0122] In some embodiments, the present disclosure encompasses methods for manufacturing any use herein (e.g., an adhesive, a coating, a film, a plastic, a composite, an electronic device, an energy storage device, an energy generation device, and the like) by applying a composition herein (e.g., any foregoing compound) in the assembly of the adhesive, the coating, the film, the plastic, the composite, the electronic device, the energy storage device, or the energy generation device. In other embodiments, the composition is provided as a polymer curative.

EXAMPLES

Example 1: Copolymers from Amino Acid Dimers and Hydroxy Acid Dimers

[0123] The composition herein can be employed to provide a copolymer. In one instance, amino acids or hydroxy acids are employed to provide cyclic derivatives, which can be further functionalized with polymerizable moieties. Exemplary polymerizable moieties include, e.g., hydroxyl, halo, amino, cyanato, isocyanato, cyano, isocyano, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted (hetero)cycloalkyl, or optionally substituted epoxy groups.

[0124] FIG. 1 shows exemplary cyclic derivatives, including a cyclic lactide formed from hydroxymandelic acid (e.g., 4-hydroxymandelic acid), a cyclic dimer formed from tyrosine, a cyclic dimer formed from hydroxyproline (e.g., 4-hydroxyproline), and a cyclic dimer formed from serine. Amino acids, when employed, can have any useful stereochemistry (e.g., L- or D-amino acids). As seen in FIG. 2, bioreachable molecules, such as amino acids, can be further functionalized to provide polymerizable moieties, such as halo, alkenyl, and alkenyl groups.

Example 2: Ion-Free Resins from Amino Acids

[0125] The compositions herein can be employed to provide an ion-free resin. For instance, amino acids can be employed to produce cyclic derivatives, which can be further functionalized with one or more unsaturated alkyl moieties, such as vinyl, allyl, or homoallyl moieties attached to a side chain of the amino acid. These unsaturated alkyl moieties can then be epoxidized with an oxidation reagent, thereby providing a cyclic ether group. In particular, these reactions can be conducted to minimize ion content, which can provide higher purity monomers and polymers.

[0126] Such ion-free resins (e.g., having a total ion content less than about 1 part per thousand) can be employed as an ingredient or a monomer in any useful composition or material. Illustrative compositions and materials include, e.g., coatings, adhesives, films, and plastics in the construction of electronics, industrial adhesives, architectural adhesives and coatings, civil engineering adhesives and coatings, transportation adhesives and coatings, handheld devices, smart phones, laptops, tablets, displays, sensors, semi-conductor chip patterning, manufacturing, and packaging.

Example 3: Non-Limiting Synthesis of Tyrosine Dimer

[0127] ##STR00058##

[0128] In a 3 L two-neck round bottom flask equipped with magnetic stirrer and overhead condenser, 200 g of Tyr-OH and 800 ml of ethylene glycol were mixed, and the flask was placed in silicon oil bath. The oil bath was heated to 190° C., and the reaction mixture was stirred for 7 hours (h). The conversion of starting material was followed up by HPLC. After 7 h, the reaction mixture was cooled down to room temperature, and the precipitated solid was filtered and washed with ethanol (2×200 ml). The solid was then dried in vacuum oven and used as is for the next step. (Yield: 64%)

Example 4: Non-Limiting Synthesis of 4-Hydroxy-Proline Dimer

[0129] ##STR00059##

[0130] In a two-neck 1 L round bottom flask equipped with magnetic stirrer and overhead condenser, 100 g of trans-4-hydroxy-L-proline and 200 ml of ethylene glycol were mixed, and the flask was placed in silicon oil bath. The oil bath was heated to 190° C., and the reaction mixture was stirred for 7 h. After 7 h, the reaction mixture was cooled down to room temperature, and the precipitated solid was filtered and washed with acetone (2×100 ml). The solid was then dried in vacuum oven. (Yield: 44%, isolated 37.95 grams of product) NMR .sup.1H NMR (D.sub.2O): 4.75 (d, 1H), 4.63 (d, 1H), 3.69 (d, 1H), 3.537 (d, 1H), 2.33 (d, 1H), 2.20 (d, 1H).

Example 5: Non-Limiting Stepwise Synthesis of Tyrosine Dimer

[0131] The following route could be applicable for dimers from different amino acids.

##STR00060##

Step 1: Preparation of (S)-methyl 2-((R)-2-((tert-butoxycarbonyl)amino)-3-(4-hydroxyphenyl) propanamido)-3-(4-hydroxyphenyl)propanoate

[0132] A 1 L reactor equipped with a magnetic stirrer, temperature probe, and nitrogen inlet was charged with ((S)-2-((tert-butoxycarbonyl)amino)-3-(4-hydroxyphenyl)propanoic acid (33.2 g, 118 mmol), (S)-methyl 2-amino-3-(4-hydroxyphenyl)propanoate (20 g, 102 mmol), hexafluorophosphate benzotriazole tetramethyl uronium (“HBTU,” 48.3 g, 127 mmol) and DMF (120 mL). The solution was stirred for 15 minutes and then cooled to 0° C. Triethylamine (42.6 mL, 306 mmol) was added to the mixture over 15 minutes. After the addition was completed, the cooling bath was removed, and the reaction was stirred overnight. After 18 h, the HPLC of the aliquot showed complete conversion of the starting materials. One hundred mL of water was slowly added to the reaction at 0° C. After stirring for 30 minutes (min), the mixture was diluted with EtOAc (150 mL), and the layers were separated. The organic layer was washed with aqueous sodium carbonate (10%, 3×50 mL) and finally with brine (50 mL). The organic layer was then dried over anhydrous sodium sulfate, filtered, and concentrated to dryness to afford the desired product as a thick oil. The product was used in the next step without further purification.

##STR00061##

Step 2: Preparation of 3,6-bis(4-hydroxybenzyl)piperazine-2,5-dione

[0133] A 3 L single-neck reactor was charged with (S)-methyl 2-((R)-2-((tertbutoxycarbonyl)amino)-3-(4-hydroxyphenyl)propanamido)-3-(4-hydroxyphenyl)propanoate (42 g, 91.6 mmol) and formic acid (420 mL), the mixture was stirred at ambient temperature for 5 h, and the formic acid and s-butanol were removed under reduced pressure. The residue was dissolved in sec-butanol (1600 mL) and toluene (400 mL), and the solution was refluxed for 3 h. The reaction was monitored by HPLC and, after the reaction was completed, the reaction mixture was concentrated to yield the crude material as an off-white solid. The crude material was dissolved in 5% NaOH in water at 5° C. and extracted with 250 ml of ethyl acetate. The aqueous layer was acidified to pH 3 by the slow addition of 10% HCl (aq). The solid material was separated by filtration, washed with water, and dried under vacuum. The solid was suspended in 200 ml of acetonitrile and filtered again and dried to get a white solid as a pure product. (Yield: 22 g, 73%). NMR 1H NMR (DMSO): 9.20 (s, 1H), 7.76 (s, 1H), 6.84 (d, J=8.4 Hz, 2H), 6.67 (d, J=8.5 Hz, 2H), 3.85 (s, 1H), 2.55-2.51 (m, 1H), 2.12 (d, J=6.6 Hz, 1H).

##STR00062##

Step 3: Preparation of 3,6-bis(4-(oxiran-2-ylmethoxy)benzyl)piperazine-2,5-dione

[0134] A 1 L single-neck reactor was charged with 3,6-bis(4-hydroxybenzyl)piperazine-2,5-dione (2 g, 6.13 mmol) and DMSO (30 mL), and the mixture was stirred at ambient temperature for 30 min in order to allow the starting materials to dissolve. Potassium carbonate (3.4 g, 24.52 mmol) was added. and the stirring was continued for 30 minutes. Epibromohydrin (1.6 mL, 18.40 mmol) was then added. and the reaction mixture was stirred for 2 days at room temperature. The reaction mixture was filtered to remove the solids and the solid was rinsed with DMSO (20 mL). The filtrate solution obtained was slowly poured into ice cold water (100 ml). The solid was filtered, washed with water (100 ml), and dried under vacuum. The solid was suspended in 120 ml of acetonitrile, filtered, and the solid was dried under vacuum to yield an off-white solid. (Yield: 1.9 g, 71%). NMR-GLC19575 .sup.1H NMR (DMSO): 7.86 (s, 1H), 6.95 (d, J=8.5 Hz, 2H), 6.87 (d, J=8.5 Hz, 2H), 4.31, 4.21 (m, 1H), 3.93 (s, 1H), 3.77 (dt, J=11.1, 6.2 Hz, 1H), 3.28 (d, J=2.6 Hz, 1H), 2.80 (t, J=4.6 Hz, 1H), 2.67 (s, 1H), 2.56 (dd, J=13.7, 4.4 Hz, 1H), 2.23 (dd, J=13.6, 6.0 Hz, 1H).

##STR00063##

Step 4: Preparation of 1,4-bis(2-ethylhexyl)-3,6-bis(4-(oxiran-2-ylmethoxy)benzyl)piperazine-2,5-dione

[0135] A 1 L single-neck reactor was charged with 3,6-bis(4-(oxiran-2-ylmethoxy)benzyl) piperazine-2,5-dione (10 g, 22.83 mmol) and dry DMSO (100 mL). The solution was stirred at ambient temperature for 30 minutes until a clear solution was obtained. Cesium carbonate (33.5 g, 102.7 mmol) was added, and the stirring was continued for 30 minutes. Then, 3-ethyl-1-iodohexane (14.4 mL, 79.9 mmol) was added to the mixture, and the reaction mixture was stirred for 2 days. After 2 days, the HPLC of the aliquot showed more than 90% of the starting material was converted. The reaction mixture was filtered to remove the solids, the solids were rinsed with MTBE (100 mL), and the filtrate was slowly poured into 120 ml of ice cold water. The organic layer was separated and washed with 80 ml of water and 80 ml of brine. The solution was dried over sodium sulfate and concentrated under vacuum to yield the crude product as a yellow oil, which was purified by column chromatography using EtOAc/hexane/Et3N mixture. A yellow, clear oil was obtained. (Yield: 2.6 g, 17%) NMR-GLC 20547 .sup.1H NMR (CDCl.sub.3): 7.03 (d, J=8.4 Hz, 2H), 6.87 (d, J=8.3 Hz, 2H), 4.13 (t, J=9.2 Hz, 3H), 3.90 (dd, J=11.0, 5.5 Hz, 2H), 3.26-3.31 (m, 1H), 2.85 (t, J=4.5 Hz, 2H), 2.68-2.71 (m, 1H), 2.26-2.40 (m, 2H), 1.26, 0.98 (m, 9H), 0.84 (t, J=7.2 Hz, 3H), 0.78 (t, J=7.4 Hz, 2H), 0.71 (t, J=7.1 Hz, 2H).

Example 6: General Reaction for N-Alkylation

[0136] The foregoing method was repeated with 2-ethylhexyl iodide replaced for iodohexane, iodooctane, iododecane, and iodododecane; and the corresponding N-alkyl derivatives were obtained in yields between 17 and 53%.

[0137] For alkylation yielding the N-oleyl derivative, an Appel reaction procedure was implemented to prepare oleyl iodide. A round-bottom flask with stir bar was rendered dry by heating to 140° C. Based on a 10 gram scale of oleyl alcohol, 1.1 equivalent (eq.) of PPh.sub.3, 1.2 eq of iodine, and 1.1 eq of imidazole were weighted out and added to the round bottom flask which was then closed with a septa. Then, 70 mL of DCM was added, and the mixture was stirred vigorously. Ten grams of oleyl alcohol were added dropwise to the mixture. The mixture took on a yellow-orange color. The reaction was stirred for 2 days. After the reaction was confirmed to have reached completion by TLC, 20 mL of solid thiosulfate (10% w/v) was added. The organic layer was collected and washed twice with 20 ml of sodium thiosulfate, followed by washings with 30 ml of water and 30 ml of brine, dried over magnesium sulfate, then filtered over paper. The filtrate was concentrated in vacuo to form a white solid. The white solid was triturated with pentane, filtered over glass wool and concentrated in vacuo to form a yellow oil.

Example 7: Non-Limiting Stepwise Synthesis of p-Hydroxyphenyl-Glycine Dimer

[0138] ##STR00064##

[0139] (2R)-2-Amino-2-(4-hydroxyphenyl)acetic acid (1.00 eq, 1.00 g, 5.98 mmol) was dissolved in 1,4-dioxane (24 mL), water (24 ml), and 12.5 ml of an aqueous 2M NaOH solution in a 100 ml 2 neck flask under nitrogen. Di-tert-butyl dicarbonate (1.00 eq, 1.31 g, 5.98 mmol) was added to the solution dropwise, and the reaction was allowed to stir for 16 hours at room temperature. The reaction mixture was concentrated then acidified to pH 2 with 5M HCl, then extracted with ethyl acetate, and washed with a 5% sodium carbonate solution and brine. The organic layers were dried over magnesium sulfate, filtered, then concentrated in vacuo. Finally, 2-(tert-butoxycarbonylamino)-2-(4-hydroxyphenyl)acetic acid [4-HPG N-Boc] (1.08 g, 4.03 mmol, 67.36% yield) was isolated as a pink tacky solid and used in the next step without further purification.

##STR00065##

[0140] rac-(2R)-2-amino-2-(4-hydroxyphenyl)acetic acid (1.00 eq, 1.00 g, 5.98 mmol) was dissolved in 20 ml of 1.25M HCl in methanol and stirred at 70° C. for 3 hours. Then, the solvent was evaporated on a rotovap to yield 1.064 g of crude pink-white solid. This solid was washed with 250 ml of saturated sodium carbonate and extracted with ethyl acetate (4×100 ml) to provide 4-hydroxyphenyl-glycine methyl ester [4-HPG OMe]. (Yield: 33.766%, isolated 0.366 g of product).

##STR00066##

[0141] 4-hydroxyphenyl-glycine methyl ester (4-HPG OMe), 4-HPG N-Boc, HBTU, and DMAc were added to a 25 ml 2 neck round bottom flask and stirred for 15 min at room temperature under nitrogen. The reaction was cooled to 0° C., and trimethylamine (0.70 ml) was added dropwise over 15 min and then allowed to stir overnight. The reaction was then quenched with 2 ml of ice cold water, stirred for 10 mins and extracted 3× with EtoAc (2 ml). The organic layers were washed with 5% sodium carbonate and then brine, dried, and concentrated.

##STR00067##

[0142] A 3 L single-neck reactor was charged with the foregoing dipeptide peptide (0.31 g) and formic acid (2.1 mL), and the mixture was stirred at ambient temperature for 5 h. Formic acid was removed under reduced pressure by azeotropic distillation with toluene. The residue was dissolved in sec-butanol (7.5 mL) and toluene (2.5 mL), and the solution was refluxed for 3 hours. The reaction mixture was concentrated to yield the crude material as a yellow-white solid.

OTHER EMBODIMENTS

[0143] While the invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modifications and this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure that come within known or customary practice within the art to which the invention pertains and may be applied to the essential features hereinbefore set forth, and follows in the scope of the claims.

[0144] Other embodiments are within the claims.