Methods for producing stereoisomerically enriched carbohydrate-based surfactants

Patent metadata

Field	Value
Publication number	US-2022017556-A1
Application number	US-202117489477-A
Country	US
Kind code	A1
Filing date	Sep 29, 2021
Priority date	Nov 16, 2012
Publication date	Jan 20, 2022
Grant date	—

Abstract

The present disclosure discusses methods for producing stereoisomerically enriched carbohydrate-based surfactants. In particular, methods of the invention include producing stereoisomerically enriched hydrophobic portion of the carbohydrate-based surfactants.

First claim

What is claimed is:

1 . A stereoselective method for producing a protected carbohydrate-based surfactant of the formula:

said method comprising: contacting an enantiomerically enriched alcohol compound of the formula:

with a protected carbohydrate under conditions sufficient to form a covalent bond between said carbohydrate and said compound of Formula A to produce said protected carbohydrate-based surfactant of Formula I, wherein
a carbohydrate of said protected carbohydrate is selected from the group consisting of a monosaccharide, a disaccharide, a trisaccharide and a derivative thereof,
Y 1 is selected from the group consisting of hydrogen, ethylenyl, ethynyl, halide, —SH, —NH 2 , and —CO 2 R s ;
R z1 is hydrogen, alkyl, benzyl, or a carboxylic acid protecting group;
R s is hydrogen or alkyl;
x 1 is an integer from 5 to 30; and
* is a chiral center.

2 . The stereoselective method according to claim 1 , wherein said enantiomerically enriched alcohol compound of Formula A is produced by an enzymatic kinetic resolution, wherein said enzymatic kinetic resolution comprises contacting a compound of the formula:

with an esterase in the presence of an ester compound of the formula R a O—C(═O)—R x under conditions sufficient to produce a mixture of an enantiomerically enriched alcohol compound of the formula:

and an enantiomerically enriched ester compound of the formula:

wherein
R a is methyl,
R x is alkyl, typically methyl or ethyl, and
x 1 , Y 1 , and R z1 are those defined in claim 1 ,

and wherein
when compound of Formula A-2 a has a same stereochemistry as compound of Formula A then separating said compound of Formula A-2 a from said mixture to obtain said enantiomerically enriched alcohol compound of Formula A; and
when said compound of Formula A-2 b has a same stereochemistry as compound of Formula A, then:
(i) separating compound of Formula A-2 b from said mixture;
(ii) producing said enantiomerically enriched alcohol compound of Formula A by hydrolyzing an ester group of said compound of Formula A-2 b .

3 . The stereoselective method according to claim 2 , wherein said enzymatic kinetic resolution produces at least 90% ee enriched compound of Formula A.

4 . The stereoselective method according to claim 2 , wherein said esterase comprises a triacylglycerol acyl hydrolase-EC 3.1.1.3 (lipase).

5 . The stereoselective method according to claim 1 further comprising the steps of deprotecting said protected carbohydrate to produce a surfactant carbohydrate of the formula:

wherein Y 1 , x 1 , and * are those defined in claim 1 .

6 . The stereoselective method according to claim 1 further comprising the steps of:
(i) when R z1 of said compound of Formula I is alkyl, benzyl, or a carboxylic acid protecting group, then hydrolyzing R z1 of said compound of Formula I under conditions sufficient to produce an enantiomerically enriched carboxylic acid compound of the formula:

(ii) reacting said enantiomerically enriched carboxylic acid of Formula I-B with a lipid of the formula:

under conditions sufficient to produce a di-lipid carbohydrate of the formula:

wherein
Y 1 , x 1 , and * are those defined in claim 1 ;
Y 2 is selected from the group consisting of hydrogen, ethylenyl, ethynyl, halide, —SH, —NH 2 , and —CO 2 R s2 ;
R z2 is hydrogen, alkyl, benzyl, or a carboxylic acid protecting group;
R s2 is hydrogen or alkyl; and
x 2 is an integer from 5 to 30.

7 . The stereoselective method according to claim 6 further comprising the steps of deprotecting said protected di-lipid carbohydrate of Formula II to produce an enantiomerically enriched surfactant di-lipid carbohydrate of the formula:

wherein
Y 1 is selected from the group consisting of hydrogen, ethylenyl, ethynyl, halide, —SH, —NH 2 , and —CO 2 H;
x 1 is an integer from 5 to 30;
* is a chiral center;
Y 2 is selected from the group consisting of hydrogen, ethylenyl, ethynyl, halide, —SH, —NH 2 , and —CO 2 H; and
x 2 is an integer from 5 to 30.

8 . The stereoselective method according to claim 6 , wherein said enantiomerically enriched alcohol compound of Formula B is produced by an enzymatic kinetic resolution, wherein said enzymatic kinetic resolution comprises contacting a compound of the formula:

with an esterase in the presence of an ester compound of the formula R a O—C(═O)—R x under conditions sufficient to produce a mixture of an enantiomerically enriched alcohol compound of the formula:

and an enantiomerically enriched ester compound of the formula:

wherein
R a is methyl,
R x is alkyl, typically methyl or ethyl, and
x 2 , Y 2 , and R z2 are those defined in claim 6 ,

and wherein
when compound of Formula B-2 a has a same stereochemistry as compound of Formula B then separating said compound of Formula B-2 a from said mixture to obtain said enantiomerically enriched alcohol compound of Formula B; and
when said compound of Formula B-2 b has a same stereochemistry as compound of Formula B, then:
(i) separating compound of Formula B-2 b from said mixture;
(ii) producing compound of Formula B by hydrolyzing an ester group of said compound of Formula B-2 b .

9 . The stereoselective method according to claim 8 , wherein said enzymatic kinetic resolution produces at least 90% ee of compound of Formula B.

Assignees

• Univ Arizona

Inventors

• Pemberton Jeanne E
• Roberts Tyler

Classifications

• C07H15/04

  attached to an oxygen atom of the saccharide radical · CPC title

• C07H15/06

  being a hydroxyalkyl group esterified by a fatty acid · CPC title

• C07H1/00 Primary

  Processes for the preparation of sugar derivatives · CPC title

• C07F3/003

  without C-Metal linkages · CPC title

• C07F9/94

  Bismuth compounds · CPC title