NON-IONIC AMPHIPHILES AND METHODS OF MAKING THE SAME

Abstract

Sugar-derived tetrol, non-ionic amphiphilic amine-esters are prepared facilely and efficaciously in a few steps. The process is initiated by the esterification of a sugar-derived tetrol with a fatty acid chloride, then, undergoing triflate esterification followed by nucleophilic displacement of the aforementioned hydrophilic amine. Each synthetic pathway is efficient and affords modest to high yields of target amphiphiles, which are valorized as practicable surfactant surrogates to petroleum incumbents.

Claims

1) An esterified reduced hexane polyol selected from the group consisting of: ##STR00004## wherein R is a carbon side chain of a fatty acid.

2) The compound of claim 1, where said carbon side chain is between 8 and 30 carbons.

3) A method of making a compound of claim 1, comprising contacting a reduced hexane polyol with a fatty acid chloride in the presence of a nucleophilic base under ambient conditions.

4) The method of claim 3, wherein the fatty acid chloride is C.sub.8-C.sub.30.

5) The method of claim 3, wherein the nucleophilic base is at least one of pyridine, dimethylaminopyridine, imidazole or a tertiary amine.

6) The method of claim 3, wherein the reduced hexane polyol is contacted with the fatty acid chloride at a temperature of from about 0° C. to about 50° C.

7) The method of claim 3, wherein the reduced hexane polyol is contacted with the fatty acid chloride at a temperature of about 25° C.

8) A sulfonated hexane ester compound selected from the group consisting of: ##STR00005## wherein R is a carbon side chain of a fatty acid and Z is a sulfonate ester moiety.

9) The compound of claim 8, wherein said carbon side chain is between 8 and 30 carbons.

10) The compound of claim 8, wherein the moiety of the sulfonated hexane ester is selected from the group consisting of p-toluenesulfonyl (tosyl), methanesulfonyl, (mesyl), ethanesulfonate (esyl), benzenesulfonate (besyl), p-bromobenzenesulfonate (brosyl), and triflouromethanesulfonic anhydride (triflate).

11) A method of making a compound of claim 8, comprising contacting an esterified, reduced hexane polyol with a sulfonating agent to form the sulfonate ester moiety.

12) The method of claim 11, wherein the sulfonating agent selected from the group consisting of p-toluenesulfonyl (tosyl), methanesulfonyl, (mesyl), ethanesulfonate (esyl), benzenesulfonate (besyl), p-bromobenzenesulfonate (brosyl), and triflouromethanesulfonic anhydride (triflate).

13) The method of claim 11, wherein the contacting is done in the presence of an organic solvent selected from the group consisting of chloroform, tetrahydrofuran, acetone, benzene, diethyl ether, and methylene chloride.

14) The method of claim 11, wherein said sulfonated hexane ester compound is contacted with the sulfonating agent at a temperature of from about −20° C. to about 26° C.

15) The method of claim 11, wherein said sulfonated hexane ester compound is contacted with the sulfonating agent at a temperature of about 0° C.

16) A amphiphilic compound selected from the group consisting of: ##STR00006## wherein R is a carbon side chain of a fatty acid with between 8 and 30 carbons and X is an organic substituent having sufficient hydrogen bonding capacity to make the compound amphiphilic.

17) (canceled)

18) A method of making an amphiphilic compound of claim 16, comprising contacting a sulfonate ester moiety of a sulfonated hexane ester with a primary amine to displace said sulfonate ester moiety with the primary amine.

19) The method of claim 18, further comprising said contacting is done in the presence of polar solvent selected from the group consisting of dimethylsulfoxide, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, acetonitrile, methanol, ethanol, and acetone.

20) The method of claim 18, wherein said sulfonate ester moiety is contacted with said primary amine at a temperature from about 30° C. to about 100° C.

21) The method of claim 18, wherein said sulfonate ester moiety is contacted with said primary amine at a temperature of about 50° C.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0017] FIG. 1 depicts the reduction of sorbitol to 1,2,5,6-hexanetetrol.

[0018] FIG. 2 depicts the acylation of 1 or 2 of the —OH moieties of 1,2,5,6-hexanetetrol with C.sub.8-C.sub.30 saturated or unsaturated acid chloride in the presence of a nucleophilic base.

[0019] FIG. 3 depicts the sulfonation of vestigial —OH moieties of 1,2,5,6-hexanetetrol mono and di-esters with trifluoromethane-sulfonate (triflate), affording a potent nucleofuge.

[0020] FIG. 4 depicts triflated (or sulfonated) 1,2,5,6-hexane esters undergoing nucleophilic displacement reactions with a hydrophilic amino reactant in an inert polar solvent, producing the targeted 1,2,5,6-hexane ester non-ionic amphiphiles.

[0021] FIG. 5A & B depict the general scheme for HTO esterification.

[0022] FIG. 6A & B depict the general scheme for sulfonation of HTO-esters.

[0023] FIG. 7 depicts the general scheme for amphipathic HTO variants.

[0024] FIG. 8 depicts the preparation of HTO-palmitate amphiphiles as shown in Example 1, Reaction Scheme of Synthesis and isolation of HTO mono, di, tri and tetrapalmitates as seen in Step 1.

[0025] FIG. 9 depicts the preparation of HTO-palmitate amphiphiles as shown in Example 1, Reaction Scheme of Triflation of HTO mono and dipalmitates as seen in Step 2.

[0026] FIG. 10 depicts the preparation of HTO-palmitate amphiphiles as shown in Example 1, Reaction Scheme of AEEA-derivitized HTO mono and dipalmitates as seen in Step 3.

[0027] FIG. 11 depicts the preparation and isolation of HTO-oleate amphiphiles as shown in Example 2, Reaction Scheme of Synthesis and isolation of HTO mono, di, tri and tetraoleates as seen in Step 1.

[0028] FIG. 12 depicts the preparation and isolation of HTO-oleate amphiphiles as shown in Example 2, Reaction Scheme of Triflation of HTO mono and dioleates as seen in Step 2.

[0029] FIG. 13 depicts the preparation and isolation of HTO-oleate amphiphiles as shown in Example 2, Reaction Scheme of AEE derivitized HTO mono and dioleates as seen in Step 3.

DEFINITIONS

[0030] In order to provide clear and consistent understanding of the specification and claims, including the scope to be given such terms, the following definitions are provided. It is also to be noted that the term “a” and “an” entity, refers to one or more or that entity; for example “a mild reducing agent,” is understood to represent one or more mild reducing agents.

[0031] About. In the present application, including the claims, other than in the operating examples or where otherwise indicated, all numbers expressing quantities or characteristics are to be understood as being modified in all instances by the term “about”. Accordingly, unless indicated to the contrary, any numerical parameters set forth in the following description may vary depending on the desired properties one seeks to obtain in the compositions and methods according to the present disclosure. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter described in the present description should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0032] Ambient temperature. As used herein, the term ambient temperature refers to the temperature of the surroundings and will be the same as room temperature indoors.

[0033] Amphiphile. As used herein, the term amphiphile refers to a term describing a chemical compound possessing both hydrophilic (water-loving, polar) and lipophilic (fat-loving) properties. Such a compound is called amphiphilic or amphipathic.

[0034] Hydrophilic. As used herein, the term hydrophilic describes a compound having a tendency to mix with, dissolve in, or be wetted by water.

[0035] Overnight. As used herein, the term overnight refers to a time frame of between 10 and 20 hours, typically about 16 hours.

[0036] Neat. As used herein, the term neat refers to the absence of a solvent in a reaction.

[0037] Room temperature. As used herein, the term room temperature refers to a temperature that is between 20° C. and 26° C., with an average of about 23° C.

[0038] PTFE. As used herein refers to Polytetrafluoroethylene.

[0039] AEEA. As used herein refers to 2-((2-aminoethyl)amino)ethanol.

[0040] AEE. As used herein refers to 2-(2-aminoethoxy)ethanol.

DETAILED DESCRIPTION OF THE INVENTION

[0041] Derived primarily from sorbitol, the deoxygenated product 1,2,5,6-hexanetetrol is a reduced hexane polyol and embodies a versatile yet relatively unexplored substrate, owing to its commercial unattainability and serves as an example in this disclosure of a reduced hexane polyol. As a reagent, this molecular entity is attractive by virtue of its inherent chirality and tetrafunctionality, which enables multi-faceted, target orientated synthetic approaches to be effected in the generation of manifold materials with favorable chemical properties, such as polymer subunits, plasticizers, lubricants, dispersants, emulsifiers, adhesives coatings, resins, humectants and surfactants.

[0042] The present disclosure describes, in part, a highly efficient, three-step preparation of reduced hexane polyol based amphiphilic compound. For exemplary purposes, 1,2,5,6-hexanetetrol was used herein. Examples of other reduced hexane polyols include, but is not limited to mono-deoxygenated hexane polyols, di-deoxygenated hexane polyols, tri-deoxygenated hexane polyols, hexane glycols and hexanols. According to one embodiment of this disclosure, the process involves esterification of one or two of the —OH moieties with a fatty acid chloride containing 8-30 carbons carried out under ambient conditions in the presence of a nucleophilic base.

[0043] In the example of 1,2,5,6 hexanetetrol, the esterification is an alcohol acylation, which can be effectuated by several methods, including but not limited to Fischer esterification and Steglich esterification. The means used as exemplary in this disclosure entailed use of labile acid chlorides by Fischer esterification, however, any esterification method could be used.

[0044] Acid chloride acylation can result in copacetic yields of corresponding 1,2,5,6-hexane mono, di, tri, and tetra esters as manifest in the examples included herein.

[0045] The process is able to produce 1,2,5,6-hexane esters from one or more of the hydroxyl groups of 1,2,5,6 hexane tetrol in reasonably high molar yields of at least 95%, typically about 50% or 55% or 60-65% or 70%.

[0046] The esterification reaction is usually conducted in the temperature range of 0-50° C., typically 10° C. or 40° C., preferably 20 or 30° C., more preferably at about 25° C.

[0047] The esterification reaction requires a nucleophilic base to furnish high yields, such as dimethylaminopyridine, imidazole, and pyrazole, but preferably pyridine, owing to its facility of removal.

[0048] According to another embodiment, the vestigial —OH moieties of 1,2,5,6-hexanetetrol mono and di-esters are sulfonated with a sulfonating agent. The sulfonating agent is selected from the group consisting of p-toluenesulfonyl (tosyl), methanesulfonyl, (mesyl), ethanesulfonate (esyl), benzenesulfonate (besyl), p-bromobenzenesulfonate (brosyl), and triflouromethanesulfonic anhydride (triflate). For proof on concept in the present disclosure, the sulfonating agent trifluoromethanesulfonic anhydride was used.

[0049] The sulfonating reaction is conducted in an inert organic solvent with a high vapor pressure, such as chloroform, tetrahydrofuran, acetone, benzene, diethyl ether, but preferably methylene chloride and is conducted at temperatures between −20° C. and room temperature, typically between −10° C. and 10° C., but preferably at about 0° C.

[0050] The molar yields of 1,2,5,6-hexanetriflate esters is quantitative or near so.

[0051] According to an exemplary embodiment, a triflated sulfonated hexane ester undergoes a nucleophilic displacement reaction with a hydrophilic, primary amine in an inert polar solvent, producing the targeted non-ionic amphiphilic compound.

[0052] The hydrophilic primary amine is exemplified with AEE, and AEEA (NH.sub.2CH.sub.2CH.sub.2O—, NH.sub.2CH.sub.2CH.sub.2NH—) which contain sufficient internal oxygen, nitrogen atoms to render the final compound amphiphilic.

[0053] The nucleophilic substitution is conducted in an inert, polar solvent with a dielectric constant (ε.sub.r>20), such as dimethylsulfoxide, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, acetonitrile, methanol, ethanol, and acetone.

[0054] The reaction temperature is between 30° C. and 100° C., typically 40° C. and 80° C., preferably at about 50° C.

[0055] The molar yields of amphipathic 1,2,5,6-hexane esters are greater than about 50%, commonly 55-95%, preferably greater than 85%.

EXAMPLES

[0056] The following examples are furnished as demonstrative of the diverse aspects of the present disclosure, with the recognition that altering parameters and conditions, for example by change of temperature, time and reagent amounts, and particular starting species and catalysts and amounts thereof, can affect and extend the full practice of the invention beyond the limits of the examples presented.

[0057] The following examples refer to 1,2,5,6-hexanetetrol and limited fatty acids for reasons of facility; however, the scope of the invention is not necessarily relegated to those specific embodiments that introduce as other more common or commercially available fatty acid species. Example 1 divulges the synthesis of 1,2,5,6-hexane palmitate amphiphiles in three steps. Examples 2 shows the synthesis of 1,2,5,6-hexane oleate amphiphiles in three steps.

Example #1

Preparation of HTO-Palmitate Amphiphiles

[0058] Step #1 Synthesis and Isolation of HTO Mono, Di, Tri and Tetrapalmitates

[0059] Reaction scheme can be seen in FIG. 8

[0060] Experimental: A 100 mL round bottomed flask equipped with a PTFE magnetic stir bar was charged with 2.00 g of HTO (13.33 mmol), 10.98 g palmitoyl chloride (39.95 mmol, 3 eq), 10 mL of pyridine and 50 mL of chloroform. A reflux condenser was attached to the flask, and while vigorously stirring, the mixture was brought to reflux which persisted overnight. After this time, excess pyridine and chloroform were removed via rotary evaporation, leaving 12.43 g of a yellow syrup, which was taken up in a minimal amount of methylene chloride and charged to a pre-fabricated silica get column saturated with 100% hexanes. Flash chromatography with a gradient hexanes->hexanes/ethyl acetate->ethyl acetate->ethyl acetate/methanol furnished four distinct fractions comprised of the following, with weights after drying: a) 0.58 g colorless loose oil, hexanetetrol tetrapalmitates (eluted 5:1 hexanes/ethyl acetate, TLC-cerium molybdate visualization, R.sub.f=0.52 with 5:1 hexanes/ethyl acetate), .sup.1H NMR (400 MHz, CDCl.sub.3) δ (ppm) 5.03 (m, 2H), 4.60 (m, 2H), 4.10 (m, 2H), 2.22 (m, 8H), 1.71 (m, 8H), 1.26-1.19 (m, 100 H), 0.94-0.91 (m, 12H); .sup.13C NMR (100 MHz, CDCl.sub.3) δ (ppm) 170.8, 170.6, 170.5, 72.6, 72.5, 66.4, 66.2, 35.1-28.3 (multiple signals, overlapped), 26.0, 25.8, 21.5, 21.4, 14.5, 14.3; b) 2.50 g pale yellow, loose oil, hexanetetrol tripalmitates (eluted 1:2 hexanes/ethyl acetate, TLC-cerium molybdate visualization, R.sub.f=0.40-0.45 with 1:2 hexanes/ethyl acetate), .sup.1H NMR (400 MHz, CDCl.sub.3) δ (ppm) 5.06 (m, 1H), 4.99 (dd, J=8.2 Hz, J=8.0 Hz), 4.61 (m, 1H), 4.17 (d, J=12.2 Hz, 1H), 2.24 (m, 6H), 1.69 (m, 8H), 1.40 - 1.24 (m, 76H), 0.93-0.91 (m, 9H); .sup.13C NMR (100 MHz, CDCl.sub.3) δ (ppm) 170.7, 170.5, 170.4, 77.2, 69.9, 66.8, 35.0, 34.8, 34.7, 32.5-28.0 (multiple signals, overlapped), 26.1, 26.0, 25.9, 23.5, 23.3, 23.2, 14.3; c) 3.99 g colorless, viscous oil hexanetetrol dipalmitates (eluted 9:1 ethyl acetate/methanol, TLC-cerium molybdate visualization, R.sub.f=0.32-0.39 with 9:1 ethyl acetate/methanol), .sup.1H NMR (400 MHz, CDCl.sub.3) δ (ppm) 5.56 (d, J=6.4 Hz, 1H), 5.27 (m, 1H), 4.98 (dd, J=8.2 Hz, J=8.0 Hz, 1H), 4.59 (J=12.0 Hz, J=7.6 Hz, 1H), 4.06 (dd, J=12.0 Hz, J=7.2 Hz, 1H), 3.56-3.50 (m, 3H), 2.25 (t, J=6.4 Hz, 2H), 2.23 (t, J=6.2 Hz, 2H), 1.69-1.66 (m, 4H), 1.52 (m, 1H), 1.43 (m, 1H), 1.40-1.29 (m, 48H), 0.92 (m, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3) δ (ppm) 170.9, 170.7, 73.2, 72.9, 72.0, 64.1, 35.2, 35.0, 32.0-27.8 (multiple signals, overlapped), 26.0, 25.9, 23.1, 23.0, 14.5, 14.3; d) 2.55 g clear, viscous syrup hexanetetrol mono-palmitate (eluted 1:2 ethyl acetate/methanol, TLC-cerium molybdate visualization, R.sub.f=0.27-0.30 with 1:2 ethyl acetate/methanol), .sup.1H NMR (400 MHz, CDCl.sub.3) δ (ppm) 5.41-5.37 (m, 2H), 4.96 (dd, J=8.3 Hz, J=8.1 Hz, 1H), 4.27 (J=12.0 Hz, J=7.2 Hz, 1H), 4.11 (m, 1H), 4.05 (dd, J=11.6 Hz, J=7.0 Hz, 1H), 3.55-3.51 (m, 3H), 2.25 (t, J=6.2 Hz, 2H), 1.65 (dt, J=6.4 Hz, J=6.0 Hz, 2H), 1.40-1.31 (m, 30H), 0.90 (t, J=6.4 Hz, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) δ (ppm) 171.2, 73.0, 72.2, 72.0, 68.4, 34.0, 32.1, 30.4, 30.3, 30.2, 30.1, 30.0, 29.8, 29.6, 29.5, 29.4, 29.2, 28.4, 28.1, 23.1, 14.4.

[0061] Step #2 Triflation of HTO Mono and Dipalmitates

[0062] Reaction scheme can be seen in FIG. 9

[0063] Experimental (furnished with dipalmitates): An oven-dried 100 mL round bottomed flask was charged with 2.00 g of a HTO-dipalmitate mixture (3.34 mmol), 5 mL of anhydrous pyridine and 50 mL of anhydrous methylene chloride. The homogeneous solution was cooled to ˜0° C. in an ice bath. While stirring, 1.40 mL of triflic anhydride (8.35 mmol) was added dropwise over 5 minutes. Once added, the ice bath was removed and sulfonation reaction continued overnight. After this time, excess triflic anhydride was quenched by adding 2 mL of water, and the mixture charged directly to a pre-fabricated silica gel column, where flash chromatography with a gradient hexanes/ethyl acetate eluent furnished 2.22 g of a light yellow oil, representing the triflated analogs of HTO-dipalmitates (77%), .sup.1H NMR (400 MHz, CDCl.sub.3) δ (ppm) 5.25 (m, 1H), 4.92 (m, 2H), 4.36 (dd, J=11.8 Hz, J=7.0 Hz, 1H), 4.20 (dd, J=12.2 Hz, J=6.8 Hz, 1H), 4.08 (dd, J=12.0 Hz, J=6.9 Hz, 1H), 3.91 (dd, J=12.1 Hz, J=7.0 Hz, 1H), 2.40 (t, J=6.2 Hz, 2H), 2.32 (t, J=6.4 Hz, 2H), 1.68-1.66 (m, 4H), 1.71 (m, 4H), 1.40-1.32 (m, 52H), 0.93-0.91 (m, 6H); .sup.13C NMR (100 MHz, CDCl.sub.3) δ (ppm) 171.4, 171.2, 120.1, 119.8, 87.0, 72.2, 71.4, 66.7, 35.3, 34.8, 32.2-28.1 (multiple signals, overlapped), 25.9, 25.0, 24.4, 24.0, 22.1, 14.3, 14.2.

[0064] Step #3 AEEA-Derivitized HTO Mono and Dipalmitates

[0065] Reaction scheme can be seen in FIG. 10

[0066] Experimental (example with HTO dipalmitate ditriflates): A 250 mL round bottomed flask equipped with a PTFE magnetic stir bar was charged with 2.00 g of a HTO dipalmitate tritriflate mixture (2.24 mmol), 701 mg of 2-((2-aminoethyl)amino)ethan-1-ol (AEEA, 6.73 mmol) and 100 mL of absolute ethanol. A reflux condenser was affixed to the flask and, while vigorously stirring, the mixture was held at reflux for 4 h. After this time, the orange solution was charged to a pre-fabricated column dry-packed with neutral alumina. Flash chromatography isocratic with ethanol furnished 1.28 g of the title compound as a viscous pale yellow oil (72%), .sup.1H NMR (400 MHz, CD.sub.3OD) δ (ppm) 5.22 (t, J=6.8 Hz, 1H), 4.52 (dd, J=12.1 Hz, J=7.0 Hz, 1H), 4.08 (dd, J=12.2 Hz, J=7.1 Hz, 1H), 3.60 (t, J=6.6 Hz, 4H), 2.72-2.66 (m, 10H), 2.48 (m, 2H), 2.38 (t, J=6.0 Hz, 2H), 1.72 (dt, J=8.2 Hz, J=4.6 Hz, 2H), 1.69 (dt, J=7.9 Hz, J=4.8 Hz, 2H), 1.58 (t, J=7.2 Hz, 2H), 1.40-1.31 (m, 50H), 0.93 (t, J=7.2 Hz, 3H), 0.90 (t, J=7.0 Hz, 3H); .sup.13C NMR (100 MHz, CD.sub.3OD) δ (ppm) 172.1, 171.8, 72.1, 66.7, 62.5, 62.3, 59.4, 55.1, 52.7, 52.5, 51.0, 50.8, 50.5, 50.4, 47.3, 35.1, 34.9, 32.0-27.9 (multiple signals, overlapped), 27.1, 26.9, 26.1, 25.8, 23.3, 23.1, 14.3, 14.2.

Example #2

Preparation and Isolation of HTO-Oleate Amphiphiles

[0067] Step #1 Synthesis and Isolation of HTO Mono, Di, Tri and Tetraoleates

[0068] Reaction scheme can be seen in FIG. 11

[0069] Experimental: A 100 mL round bottomed flask equipped with a PTFE magnetic stir bar was charged with 2.00 g of HTO (13.33 mmol), 12.03 g oleoyl chloride (39.95 mmol, 3 eq), 10 mL of pyridine and 50 mL of chloroform. A reflux condenser was attached to the flask, and while vigorously stirring, the mixture was brought to reflux which persisted overnight. After this time, excess pyridine and chloroform were removed via rotary evaporation, affording 12.77 g of a yellow syrup, which was taken up in a minimal amount of methylene chloride and charged to a pre-fabricated silica get column saturated with 100% hexanes. Flash chromatography with a gradient hexanes->hexanes/ethyl acetate->ethyl acetate->ethyl acetate/methanol furnished four distinct fractions comprised of the following, with weights after drying: a) 0.71 g colorless loose oil, hexanetetrol tetraoleates (eluted 6:1 hexanes/ethyl acetate, TLC-cerium molybdate visualization, R.sub.f=0.57 with 6:1 hexanes/ethyl acetate), .sup.1H NMR (400 MHz, CDCl.sub.3) δ (ppm) 5.42-5.38 (m, 8H), 5.24-5.22 (m, 4H), 4.49-4.47 (m, 4H), 4.25-4.23 (m, 4H), 2.40-2.36 (m, 8H), 2.25-2.20 (m, 16H), 1.71-1.68 (m, 8H), 1.56 (t, J=6.2 Hz, 2H), 1.53 (t, J=6.4 Hz, 2H), 1.35-1.26 (m, 80H), 0.93-0.90 (m, 12H); .sup.13C NMR (100 MHz, CDCl.sub.3) δ (ppm) 172.2, 172.1, 172.0, 132.1, 132.0, 131.8, 131.7, 131.5, 131.3, 72.1, 71.9, 67.3, 66.9, 34.1-28.5 (multiple signals, overlapped), 26.1, 25.9, 25.6, 25.5, 25.3, 23.1, 22.9, 22.8, 22.6, 14.5, 14.3; b) 2.13 g clear loose oil, hexanetetrol trioleates (eluted 1:1 hexanes/ethyl acetate, TLC-cerium molybdate visualization, R.sub.f=0.44-0.48 with 1:1 hexanes/ethyl acetate), .sup.1H NMR (400 MHz, CDCl.sub.3) δ (ppm) 5.42-5.39 (m, 6H), 5.30 (d, J=6.8 Hz, 1H), 5.05 (m, 1H), 4.46 (dd, J=12.4 Hz, J=7.2 Hz, 1H), 4.38 (dd, J=12.2 Hz, J=7.0 Hz, 1H), 4.15-4.11 (m, 3H), 2.40-2.37 (m, 6H), 2.24-2.21 (m, 12H), 1.73-1.70 (m, 6H), 1.54 (t, J=6.6 Hz, 1H), 1.51 (t, J=6.0 Hz, 1H), 1.36-1.28 (m, 66H), 0.92-0.90 (m, 9H); .sup.13C NMR (100 MHz, CDCl.sub.3) δ (ppm) 172.0, 171.8. 171.7, 132.2, 132.0, 131.9, 131.8, 131.7, 72.3, 72.0, 71.8, 67.2, 34.1-28.5 (multiple signals, overlapped), 27.9, 26.1, 23.3, 23.1, 22.9, 14.5, 14.3, 14.2; c) 4.38 g colorless, viscous oil hexanetetrol dioleates (eluted 11:1 ethyl acetate/methanol, TLC-cerium molybdate visualization, R.sub.f=0.40-0.43 with 11:1 ethyl acetate/methanol), .sup.1H NMR (400 MHz, CDCl.sub.3) δ (ppm) 5.44 (dd, J=10.2 Hz, J=4.2 Hz, 1H), 5.40 (dd, J=10.1 Hz, J=4.0 Hz, 1H), 5.36 (dd, J=10.0 Hz, J=4.4 Hz, 1H), 5.35 (dd, J=10.2 Hz, J=4.3 Hz, 1H), 5.32 (d, J=6.5 Hz, 1H), 4.94 (dd, J=12.2 Hz, J=7.0 Hz, 1H), 4.71 (m, 1H), 4.42 (dd, J=12.3 Hz, J=7.0 Hz, 1H), 4.11-4.08 (m, 2H), 3.77 (dd, J=12.0, J=4.0 Hz, 1H), 3.71 (dd, J=11.8, J=4.3 Hz, 1H), 2.41 (t, J=6.6 Hz, 2H), 2.36 (t, J=6.4 Hz, 2H), 2.22-2.18 (m, 8H), 1.72-1.69 (m, 4H), 1.52 (t, J=6.2 Hz, 1H), 1.42 (dt, J=6.8 Hz, J=4.4 Hz, 2H), 1.34-1.29 (m, 40H), 0.92 (t, J=6.2 Hz, 3H), 0.88 (t, J=6.4 Hz, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) δ (ppm) 172.0, 171.8, 132.3, 132.3, 132.0, 131.9, 74.0, 71.9, 71.7, 67.4, 34.0, 33.6, 32.9-28.7 (multiple signals, overlapped), 26.0, 25.8, 23.1, 22.5, 22.0, 14.5, 14.1; d) 2.81 g clear, viscous oil hexanetetrol monooelates (eluted 1:1 ethyl acetate/methanol, TLC-cerium molybdate visualization, R.sub.f=0.30-0.33 with 1:1 ethyl acetate/methanol). .sup.1H NMR (400 MHz, CDCl.sub.3) δ (ppm) 5.43 (dd, J=10.1 Hz, J=4.4 Hz, 1H), 5.41 (dd, J=10.3 Hz, J=4.2 Hz, 1H), 5.31 (d, J=6.8 Hz, 1H), 5.25 (d, J=6.6 Hz, 1H), 4.91 (d, J=6.2 Hz, 1H), 4.40 (dd, J=12.0 Hz, J=7.2 Hz, 1H) 4.09-4.07 (m, 2H) 3.55-3.49 (m, 3H), 2.41 (t, J=6.4 Hz, 2H), 2.20-2.18 (m, 4H), 1.71 (dt, J=7.2 Hz, J=7.0 Hz, 2H), 1.43 (m, 4H), 1.32-1.28 (m, 20H), 0.93 (t, J=6.4 Hz, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) δ (ppm) 172.1, 132.0, 131.8, 73.6, 72.0, 67.3, 33.7, 32.1, 31.9, 31.8, 31.6, 31.4, 31.3, 31.1, 29.0, 28.5, 28.4, 28.2, 26.2, 23.2, 14.4.

[0070] Step #2 Triflation of HTO Mono and Dioleates

[0071] Reaction scheme can be seen in FIG. 12

[0072] Experimental (example with HTO monooleates): An oven-dried 100 mL round bottomed flask was charged with 2.00 g of a HTO-monooleate mixture (4.82 mmol), 5 mL of anhydrous pyridine and 50 mL of anhydrous methylene chloride. The homogeneous solution was cooled to ˜0° C. in an ice bath. While stirring, 3.25 mL of triflic anhydride (19.3 mmol) was added dropwise over 5 minutes. Once added, the ice bath was removed and sulfonation reaction continued overnight. After this time, excess triflic anhydride was quenched by adding 2 mL of water, and the mixture charged directly to a pre-fabricated silica gel column, where flash chromatography with a gradient hexanes/ethyl acetate eluent furnished 3.13 g of a light yellow oil, representing the triflated analogs of HTO-monooleates (80%). .sup.1H NMR (400 MHz, CDCl.sub.3) δ (ppm) 5.47 (dd, J=10.3 Hz, J=4.0 Hz, 1H), 5.41 (dd, J=10.5 Hz, J=4.4 Hz, 1H), 5.38 (m, 1H), 4.91 (m, 1H), 4.40 (dd, J=12.2 Hz, J=6.1 Hz, 1H), 4.21 (dd, J=12.0 Hz, J=6.4 Hz, 1H), 4.16 (dd, J=12.1 Hz, J=6.6 Hz, 1H), 3.92 (dd, J=11.9 Hz, J=6.4 Hz, 1H), 2.40 (t, J=6.5 Hz, 2H), 2.19-2.16 (m, 4H), 1.70 (dt, J=7.2 Hz, J=7.0 Hz, 2H), 1.45 (m, 4H), 1.32-1.28 (m, 20H), 0.92 (t, J=6.2 Hz, 3H) ; .sup.13C NMR (100 MHz, CDCl.sub.3) δ (ppm) 171.9, 130.9, 130.7, 120.1, 119.9, 119.7, 88.0, 87.4, 71.7, 68.1, 34.6, 32.4, 31.5, 31,4, 31.2, 30.9, 30.7, 30.5, 30.3, 29.0, 28.8, 26.1, 25.5, 25.2, 23.5, 14.6.

[0073] Step #3 AEE Derivitized HTO Mono and Dioleates

[0074] Reaction scheme can be seen in FIG. 13

[0075] Experimental (with HTO monoleate, triitriflate): A 250 mL round bottomed flask equipped with a PTFE magnetic stir bar was charged with 2.00 g of a HTO monooleate, tritriflate mixture (2.47 mmol), 1.03 g of 2-((2-aminoethyl)amino)ethan-1-ol (AEEA, 9.87 mmol) and 100 mL of absolute ethanol. A reflux condenser was affixed to the flask and, while vigorously stirring, the mixture was held at reflux for 4 h. After this time, the orange solution was charged to a pre-fabricated column dry-packed with neutral alumina. Flash chromatography isocratic with ethanol furnished 1.24 g of the title compound as a viscous, clear oil (74%). .sup.1H NMR (400 MHz, CD.sub.3OD) δ (ppm) 5.44 (dd, J=10.2 Hz, J=4.4 Hz, 1H), 5.41 (dd, J=10.0 Hz, J=4.6 Hz, 1H), 4.41 (dd, J=12.2 Hz, J=6.8 Hz, 1H), 3.92 (dd, J=12.0 Hz, J=6.5 Hz, 1H), 3.60 (t, J=6.2 Hz, 2H), 3.56 (t, J=6.0 Hz, 2H), 3.54 (t, J=6.0 Hz, 2H), 3.16 (dt, J=7.2 Hz, J=7.0 Hz, 1H), 2.74-2.66 (m, 14H), 2.55-2.51 (m, 4H), 2.40 (t, J=6.2 Hz), 2.20-2.18 (m, 4H), 1.71 (dt, J=7.4 Hz, J=7.2 Hz, 2H), 1.36-1.28 (m, 24H), 0.92 (t, J=6.9 Hz, 3H) ; .sup.13C NMR (100 MHz, CD.sub.3OD) δ (ppm) 172.1, 131.1, 130.9, 69.6, 62.9, 62.5, 62.3, 60.9, 59.1, 54.8, 53.0, 52.9, 52.8, 50.5, 50.3, 50.1, 49.9, 48.0, 47.6, 35.1, 32.6, 32.0, 31.8, 31.0, 30.8, 30.6, 30.0, 29.6, 28.9, 28.7, 27.3, 25.9, 23.5, 14.0.