Method and compositions

Abstract

A method of preparing a compound of formula (III): wherein x is from 1 to 6, y is from 1 to 12, z is from 0 to 10, each M and each M′ is independently a mycolic acid residue including a β-hydroxy acid moiety and each S is a monosaccharide unit; the method comprising reacting one or more mycolic acids with one or more saccharide units wherein the hydroxyl group of each β-hydroxy acid moiety is protected prior to reaction with the one or more saccharide units.

1 . A method of preparing a compound of formula (III):
   (M) x -(S) y -(M′) z   (III)
   wherein x is from 1 to 6, y is from 1 to 12, z is from 0 to 10, each M and each M′ is independently a mycolic acid residue including a β-hydroxy acid moiety and each S is a monosaccharide unit; the method comprising reacting one or more mycolic acids with one or more saccharide units wherein the hydroxyl group of each β-hydroxy acid moiety is protected prior to reaction with the one or more saccharide units.   
     
     
         2 . A method according to  claim 1  wherein the hydroxyl group of each β-hydroxy acid moiety is protected as a silyl ether. 
     
     
         3 . A method according to  claim 1  which comprises reacting one or more mycolic acids with a disaccharide species wherein the non-reacting hydroxyl groups of the disaccharide species are protected. 
     
     
         4 . A method according to  claim 1  comprising the steps of:
 (i) protecting the hydroxyl group of the b-hydroxy acid moiety of a mycolic acid; 
 (ii) reacting the protected acid produced in step (i) with a saccharide species; 
 (iii) optionally reacting the product obtained in step (ii) with a further mycolic acid group in which the b-hydroxy acid moiety is protected; and 
 (iv) deprotecting the b-hydroxy acid moiety of the mycolic acid(s). 
 
     
     
         5 . A compound of formula (III) prepared by the method of  claim 1 . 
     
     
         6 . A compositon comprising at least 90 wt % of a single compound of formula (III):
   (M) x -(S) y -(M′) z   (III)
   wherein x is from 1 to 6, y is from 1 to 12, z is from 0 to 10, each M and each M′ is independently a mycolic acid residue including a β-hydroxy acid moiety and each S is a monosaccharide unit.   
     
     
         7 . A composition according to  claim 6  wherein x is 1, y is 2 and z is 0 or 1. 
     
     
         8 . A composition according to  claim 7  which comprises a trehalose unit. 
     
     
         9 . A composition according to  claim 6  wherein each M and M′ is independently selected from a mycolic acid residue of formula (IV): 
       
         
           
           
               
               
           
         
         wherein R is an unsubstituted alkyl chain having 16 to 30 carbon atoms; R 1  is an alkyl chain having from 12 to 24 carbon atoms; each of R 2 , R 3  and R 4  is an alkylene moiety having from 6 to 20 carbon atoms; and each of X, Y and Z is independently selected from the units shown in figure (V): 
       
       
         
           
           
               
               
           
         
       
     
     
         10 . A composition according to  claim 9  wherein Y is CH 2 , R 2  and R 3  have a combined total of from 10 to 20 carbon atoms and X includes a cyclopropyl unit. 
     
     
         11 . A composition comprising a compound of formula (III):
   (M) x -(S) y -(M′) z   (III)
   wherein x is from 1 to 6, y is from 1 to 12, z is from 0 to 10, each M and each M′ is independently a mycolic acid residue including a β-hydroxy acid moiety and each S is a monosaccharide unit; and a pharmaceutically acceptable carrier.   
     
     
         12 . A compound of formula (III):
   (M) x -(S) y -(M′) z   (III)
   wherein x is from 1 to 6, y is from 1 to 12, z is from 0 to 10, each M and each M′ is independently a mycolic acid residue including a β-hydroxy acid moiety and each S is a monosaccharide unit for use in therapy.   
     
     
         13 . A compound of formula (III):
   (M) x -(S) y -(M′) z   (III)
   wherein x is from 1 to 6, y is from 1 to 12, z is from 0 to 10, each M and each M′ is independently a mycolic acid residue including a β-hydroxy acid moiety and each S is a monosaccharide unit for use as an adjuvant in vaccination.   
     
     
         14 . The use of a compound of formula (III):
   (M) x -(S) y -(M′) z   (III)
   wherein x is from 1 to 6, y is from 1 to 12, z is from 0 to 10, each M and each M′ is independently a mycolic acid residue including a β-hydroxy acid moiety and each S is a monosaccharide unit; in a method of detecting a pathogen.