6,6'-Diesters of trehalose and process for the synthesis thereof

Claim 2

A compound selected from the group consisting of I. Compounds having the following structural formula ##STR9## wherein Y and W are monovalent radicals selected from the group consisting of -O-trityl, -O-H, -O-mesyl, -O-tosyl, desoxy bromo, desoxy iodo, and -O-acyl radicals containing 10-100 carbon atoms, and Bz in each instance is a monovalent benzyl radical; II. 6,6'-di-O-[p-(hexadecyloxy-phenyl)-4-butyryl]-trehalose; and III. 6,6'-di-O-[3,4-di-(hexadecyloxy-phenyl)-γ-butyryl]-trehalose.

Claim 3

A compound in accordance with claim 1 wherein the said compound is 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-trityl trehalose.

Claim 4

A compound in accordance with claim 1 wherein the said compound is 2,3,4,2',3',4'-hexa-O-benzyl trehalose.

Claim 5

A compound in accordance with claim 1 wherein the said compound is 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-mesyl trehalose.

Claim 6

A compound in accordance with claim 1 wherein the said compound is 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-tosyl trehalose.

Claim 7

A compound in accordance with claim 1 wherein the said compound is 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-didesoxy-dibromo trehalose.

Claim 8

A compound in accordance with claim 1 wherein the said compound is 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-didesoxy-di-iodo trehalose.

Claim 9

A compound in accordance with claim 1 wherein the said compound is 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-[p-(hexadecyloxy-phenyl)-4-butyryl]-trehalose.

Claim 10

A compound in accordance with claim 1 wherein the said compound is 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-corynomycolyl trehalose.

Claim 11

A compound in accordance with claim 1 wherein the said compound is 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-mycolyl trehalose.

Claim 12

A compound in accordance with claim 1 wherein the said compound is 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-[3,4-di-(hexadecyloxy-phenyl)-.gamma.-butyryl]trehalose.

Claim 13

A compound in accordance with claim 1 wherein the said compound is 6,6'-di-O-[p-(hexadecyloxy-phenyl)-4-butyryl]-trehalose.

Claim 14

A compound in accordance with claim 1 wherein the said compound is 6,6'-di-O-[3,4-di-(hexadecyloxy-phenyl)-γ-butyryl]-trehalose.

Claim 15

A compound in accordance with claim 1 wherein the said compound is 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose and the said acyl groups contain 10-100 carbon atoms.

Claim 16

A compound in accordance with claim 14 wherein the acyl groups are derived from mycolic acid.

Claim 17

A compound in accordance with claim 14 wherein the acyl groups are derived from corynomycolic acid.

Claim 18

A compound in accordance with claim 14 wherein the acyl groups are derived from p-hexadecyloxy-phenyl-4-butyric acid.

Claim 19

A compound in accordance with claim 14 wherein the acyl groups are derived from 3,4-di-(hexadecyloxy-phenyl)-γ-butyric acid.

Claim 20

A compound in accordance with claim 14 wherein the acyl groups are derived from a hydroxy carboxylic acid selected from the group consisting of threo-alpha-organobranched-beta-hydroxy carboxylic acid and erythro-alpha-organobranched-beta-hydroxy carboxylic acid.

Claim 21

A compound in accordance with claim 19 wherein the said alpha-organobranch of the carboxylic acid contains 10-28 carbon atoms and the remainder of the carboxylic acid molecule contains 12-30 carbon atoms.

Claim 22

A process for preparing 6,6'-diacyl esters of trehalose comprising dehexabenzylating 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose by hydrogenolysis with gaseous elemental hydrogen under pressure, the acyl groups containing 10-100 carbon atoms, the reactants in the said hydrogenolysis consisting essentially of the said 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose and elemental hydrogen, the said 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose being reacted with elemental hydrogen in the said hydrogenolysis to thereby remove all of the six benzyl radicals thereof and replace them with hydrogen and thereby produce a reaction mixture containing the corresponding 6,6'-diacyl ester of trehalose as the desired product and toluene as the by-product, and thereafter isolating the desired 6,6'-diacyl ester of trehalose thus produced from the reaction mixture.

Claim 23

A process for preparing 6,6'-diacyl esters of trehalose comprising dehexabenzylating 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose by hydrogenolysis with gaseous elemental hydrogen under pressure, the acyl groups containing 10-100 carbon atoms, the reactants in the said hydrogenolysis consisting essentially of the said 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose and elemental hydrogen, the said 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose being reacted with elemental hydrogen in the said hydrogenolysis to thereby remove all of the six benzyl radicals thereof and replace them with hydrogen and thereby produce a reaction mixture containing the corresponding 6,6'-diacyl ester of trehalose as the desired product and toluene as the by-product, and thereafter isolating the desired 6,6'-diacyl ester of trehalose thus produced from the reaction mixture.

Claim 24

The process of claim 21 wherein the said acyl groups are derived from carboxylic acids selected from the group consisting of mycolic acid, corynomycolic acid, p-hexadecyloxy-phenyl-4-butyric acid and 3,4-di-hexadecyloxy-phenyl-γ-butyric acid.

Claim 25

The process of claim 21 wherein the said acyl groups are derived from mycolic acid.

Claim 26

The process of claim 21 wherein the said acyl groups are derived from corynomycolic acid.

Claim 27

The process of claim 22 wherein the acyl groups are derived from a hydroxy carboxylic acid selected from the group consisting of threo-alpha-organobranched-beta-hydroxy carboxylic acid and erythroalpha-organobranched-beta-hydroxy carboxylic acid.

Claim 28

The process of claim 25 wherein the said alpha-organobranch of the carboxylic acid contains 10-28 carbon atoms and the remainder of the carboxylic acid molecule contains 12-30 carbon atoms.

Claim 29

A process for preparing the compound 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose comprising acylating 2,3,4,2',3',4'-hexa-O-benzyl trehalose in each of the 6 and 6' positions with an acylating agent selected from the group consisting of carboxylic acid halides and carboxylic acid anhydrides containing 10-100 carbon atoms to thereby produce 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose containing impurities, and separating the 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose thus produced from the impurities by chromatography to produce purified 2,3,4,2'3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose.

Claim 30

A process for preparing the compound 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose comprising acylating 2,3,4,2',3',4'-hexa-O-benzyl trehalose in each of the 6 and 6' positions with an acylating agent selected from the group consisting of carboxylic acid halides and carboxylic acid anhydrides containing 10-100 carbon atoms to thereby produce 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose containing impurities, and separating the 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose thus produced from the impurities by chromatography to produce purified 2,3,4,2'3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose.

Claim 31

The process of claim 27 wherein the said 2,3,4,2',3',4'-hexa-O-benzyl trehalose is prepared by hydrolyzing 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-trityl trehalose in an acidic aqueous medium to remove the trityl groups from the 6 and 6' positions without disturbing the benzyl groups in the 2,3,4,2',3',4'-positions to thereby produce 2,3,4,2',3',4'-hexa-O-benzyl trehalose containing impurities, and thereafter the 2,3,4,2',3',4'-hexa-O-benzyl trehalose thus produced is separated from impurities by chromatography.

Claim 32

The process of claim 28 wherein the said 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-trityl trehalose is prepared by benzylating 6,6'-di-O-trityl trehalose in the 2,3,4,2',3',4'-positions by reacting with benzyl halide in organic solvent solution, the said 2,3,4,2',3',4'-hexa-O-benzyl trehalose being reacted in the presence of a stoichiometric excess of benzyl halide and a base to thereby produce 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-trityl trehalose.

Claim 33

A process for preparing the compound 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose comprising acylating a compound selected from the group consisting of the 6,6'-di-O-mesyl, di-O-tosyl, didesoxy dibromo and di-iodo derivatives of 2,3,4,2',3',4'-hexa-O-benzyl trehalose in each of the 6 and 6'-positions by reacting with a salt of a carboxylic acid containing 10-100 carbon atoms, the said compound being reacted in organic solvent solution in the presence of a stoichiometric excess of the said carboxylic acid salt to thereby produce 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose containing impurities, and separating the 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose thus produced from the impurities by chromatography to produce purified 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose.

Claim 34

A process for preparing the compound 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose comprising acylating a compound selected from the group consisting of the 6,6'-di-O-mesyl, di-O-tosyl, didesoxy dibromo and di-iodo derivatives of 2,3,4,2',3',4'-hexa-O-benzyl trehalose in each of the 6 and 6'-positions by reacting with a salt of a carboxylic acid containing 10-100 carbon atoms, the said compound being reacted in organic solvent solution in the presence of a stoichiometric excess of the said carboxylic acid salt to thereby produce 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose containing impurities, and separating the 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose thus produced from the impurities by chromatography to produce purified 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-acyl trehalose.

Claim 35

The process of claim 30 wherein the said 6,6'-di-O-mesyl, di-O-tosyl, didesoxy dibromo and di-iodo derivatives of 2,3,4,2',3',4'-hexa-O-benzyl trehalose are prepared by reacting 2,3,4,2',3',4'-hexa-O-benzyl trehalose in the 6 and 6' positions with mesyl halide, tosyl halide, phosphorus bromides and phosphorus iodide, respectively.

Claim 36

The process of claim 31 wherein the said 2,3,4,2',3',4'-hexa-O-benzyl trehalose is prepared by hydrolyzing 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-trityl trehalose in an acidic aqueous medium to remove the trityl groups from the 6 and 6' positions without disturbing the benzyl groups in the 2,3,4,2',3',4'-positions to thereby produce 2,3,4,2',3',4'-hexa-O-benzyl trehalose containing impurities, and thereafter the 2,3,4,2',3',4'-hexa-O-benzyl trehalose thus produced is separated from impurities by chromatography.

Claim 37

The process of claim 32 wherein the said 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-trityl trehalose is prepared by benzylating 6,6'-di-O-trityl trehalose in the 2,3,4,2',3',4'-positions by reacting with benzyl halide in organic solvent solution, the said 6,6'-di-O-trityl trehalose being reacted in the presence of a stoichiometric excess of benzyl halide and a base at elevated temperature and for a period of time to thereby produce 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-trityl trehalose.

Claim 38

A process for preparing the compound 2,3,4,2',3',4'-hexa-O-benzyl trehalose comprising hydrolyzing 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-trityl trehalose in an acid aqueous medium to remove the trityl groups from the 6 and 6' positions without disturbing the benzyl groups in the 2,3,4,2',3',4'-positions to thereby produce 2,3,4,2',3',4'-hexa-O-benzyl trehalose containing impurities, the aqueous medium being acidified with an acid which does not permanently enter into the hydrolysis reaction and the reactants in the said hydrolysis consisting essentially of the said 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-trityl trehalose and the acidic aqueous medium, and separating the 2,3,4,2',3',4'-hexa-O-benzyl trehalose thus produced from impurities by chromatography.

Claim 39

A process for preparing the compound 2,3,4,2',3',4'-hexa-O-benzyl trehalose comprising hydrolyzing 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-trityl trehalose in an acid aqueous medium to remove the trityl groups from the 6 and 6' positions without disturbing the benzyl groups in the 2,3,4,2',3',4'-positions to thereby produce 2,3,4,2',3',4'-hexa-O-benzyl trehalose containing impurities, the aqueous medium being acidified with an acid which does not permanently enter into the hydrolysis reaction and the reactants in the said hydrolysis consisting essentially of the said 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-trityl trehalose and the acidic aqueous medium, and separating the 2,3,4,2',3',4'-hexa-O-benzyl trehalose thus produced from impurities by chromatography.

Claim 40

The process of claim 34 wherein the said 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-trityl trehalose is prepared by benzylating 6,6'-di-O-trityl trehalose in the 2,3,4,2',3',4'-positions by reacting with benzyl halide in organic solvent solution, the said 6,6'-di-O-trityl trehalose being reacted in the presence of a stoichiometric excess of benzyl halide and a base at elevated temperature and for a period of time to thereby produce 2,3,4,2',3',4'-hexa-O-benzyl-6,6'-di-O-trityl trehalose.