Studies towards a conjugate vaccine for anthrax:: Synthesis of the tetrasaccharide side chain of the Bacillus anthracis exosporium

The first synthesis of beta-L-glycoside 17 of the tetrasaccharide beta-Ant-(1 -> 3)-alpha-L-Rhap-(1 -> 3)-alpha-L-Rhap-(1 -> 2)-L-Rhap is described (Schemes 1 - 3). Its spacer can be functionalized to make it amenable to conjugation to proteins by different conjugation methods. The synthesis was performed in a stepwise manner starting from the aglycon-bearing terminal saccharide with thioglycosides as glycosyl donors. To attach the upstream terminal anthrose residue, the assembled linker-equipped trisaccharide was glycosylated with ethyl 4-azido-3-O-benzyl-2-O-(bromoacetyl)-4,6-dideoxy-1-thio-beta-D-glucopyranoside (11). Further functionalization of the tetrasaccharide thus obtained, followed by deprotection gave the target substance 17. Synthesis of substructures of 17 equipped with the same spacer, namely beta-L-Rhap-1-O-(CH2)(5)COOMe (21), alpha-L-Rhap-(1 -> 2)-beta-L-Rhap-1-O-(CH2)(5)COOMe (22), and alpha-L-Rhap-(1 -> 3)-alpha-L-Rhap-(1 -> - 2)-beta-L-Rhap-1-O-(CH2)(5)COOMe (23), is also described (Scheme 4).