Granted Patent B2

US 12,391,719 · App. 17/489,477 · Granted Aug 19, 2025

Inventors: Jeanne E. Pemberton (Tucson, AZ); Tyler Roberts (Tucson, AZ)

Assignee: ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIVERSITY OF ARIZONA

C07H15/14C07F3/003C07F9/94C07H1/00C07H15/04C07H15/06

Abstract

Claims (55)

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, and a trisaccharide;

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 s 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.

Assignments (2)

Continuity (5)

References Cited (35)