Method for 2-sulfation of glycosides

Abstract

Method for selective 2-sulfation of glycosides.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows: 
     
         1 . A method for sulfating a glycoside at the 2-position, comprising:
 (a) treating a glycoside having hydroxyl groups at positions 2 and 4 in a cis relationship with a tin reagent to provide a glycoside 2,4-stannylene acetal; and   (b) treating the 2,4-stannylene acetal with a sulfating agent to provide a 2-sulfated glycoside.   
     
     
         2 . The method of  claim 1 , wherein the 2-sulfated glycoside is sulfated at the 2-position with a selectivity is greater than 90%. 
     
     
         3 . The method of  claim 1 , wherein the 2-sulfated glycoside is sulfated at the 2-position with a selectivity is greater than 95%. 
     
     
         4 . The method of  claim 1 , wherein the glycoside is an iduronate glycoside. 
     
     
         5 . The method of  claim 1 , wherein the glycoside is an α-L-iduronate glycoside. 
     
     
         6 . The method of  claim 1 , wherein the tin reagent is a dialkyltin (VI) oxide. 
     
     
         7 . The method of  claim 1 , wherein the tin reagent is dibutyltin (IV) oxide. 
     
     
         8 . The method of  claim 1 , wherein the sulfating agent is sulfur trioxide. 
     
     
         9 . The method of  claim 1 , wherein the sulfating agent is a sulfur trioxide complex selected from the group consisting of sulfur trioxide trimethylamine complex, sulfur trioxide pyridine complex, and sulfur trioxide N,N-dimethylformamide complex. 
     
     
         10 . The method of  claim 1 , wherein the glycoside has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         11 . The method of  claim 1 , wherein 2-sulfated glycoside has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The method of  claim 11  further comprising saponifying the 2-sulfated glycoside methyl ester to provide a 2-sulfated glycoside having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         13 . The method of  claim 1 , wherein the glycoside has the formula: 
       
         
           
           
               
               
           
         
         wherein the glycoside forms a parent ion when subjected to electrospray ionization-tandem mass spectrometry, 
         M is a moiety that cleaves from the parent ion to provide a fragment ion on collision-induced dissociation, 
         L covalently links M to the glycoside moiety, and 
         R is a C1-C6 alkyl group. 
       
     
     
         14 . The method of  claim 1 , wherein 2-sulfated glycoside has the formula: 
       
         
           
           
               
               
           
         
         wherein the sulfated glycoside forms a parent ion when subjected to electrospray ionization-tandem mass spectrometry, 
         M is a moiety that cleaves from the parent ion to provide a fragment ion on collision-induced dissociation, 
         L covalently links M to the glycoside moiety, 
         R is a C1-C6 alkyl group, and 
         X is hydrogen, an ammonium ion, or a metal ion. 
       
     
     
         15 . The method of  claim 14  further comprising saponifying the 2-sulfated glycoside ester to provide a 2-sulfated glycoside having the formula: 
       
         
           
           
               
               
           
         
         wherein the sulfated glycoside forms a parent ion when subjected to electrospray ionization-tandem mass spectrometry, 
         M is a moiety that cleaves from the parent ion to provide a fragment ion on collision-induced dissociation, 
         L covalently links M to the iduronate glycoside moiety, and 
         X is hydrogen, an ammonium ion, or a metal ion. 
       
     
     
         16 . The method of  claim 14 , wherein M is a butyloxycarbonyl [C 4 H 9 OC(═O)—]. 
     
     
         17 . The method of  claim 14 , wherein L is —NH—(CH 2 ) n —NHC(═O)CH 2 —, where n is 1-8. 
     
     
         18 . The method of  claim 14 , wherein the ammonium ion is trimethylammonium. 
     
     
         19 . The method of  claim 14 , wherein the metal ion is a sodium ion.