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 polysaccharide, a branched heptasaccharide α-Neu p5Ac-(2→3)-β-d-Gal p-(1→4)-β-d-GlcN pAc-(1→3)-{[β-d-Gal p-(1→6)]-β-d-Gal p}-(1→4)-β-d-Glc p-(1→3)-β-d-Glc p-(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 α-Neu5Ac-(2→3)-β-d-Gal-(1→4)-β-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 α-Neu5Ac-(2→3)-β-d-Gal as consecutive glycosyl donors.