Chemical Synthesis of the Repeating Unit of Type II Group B Streptococcus Capsular Polysaccharide

The first chemical synthesis of the repeating unit of serotype II group B Streptococcus capsular poly-accharide, a branched heptasaccharide alpha-Neup5Ac-(2 -> 3)-beta-D-Galp-(1 -> 4)-beta-D-GlcNpAc-(1 -> 3)-{[beta-D-Galp-(1 -> 6)]-beta-DGalp}-(1 -> 4)-beta-D-Glcp-(1 -> 3)-beta D-Glcp-(1 ->, was achieved by convergent [4+2+1] glycosylation, after probing different synthetic strategies and overcoming a series of difficulties. The title compound was designed to carry a free amino group at its downstream end to enable further regioselective elaboration. This work also revealed that the alpha-Neu5Ac-(2 -> 3)-beta-D-Gal-(1 -> 4)-beta-D-GlcNAc motif, which is common in natural glycans, had a low reactivity as glycosyl donors, so it was rather difficult to directly couple this trisaccharide with sterically hindered acceptors. The motif was efficiently constructed via on-site glycan elongation using properly protected GlcN and alpha-Neu5Ac-(2 -> 3)-beta-D-Gal as consecutive glycosyl donors.