Synthesis of a single repeat unit of type VIII Group B Streptococcus capsular polysaccharide

We have synthesized a single repeat unit of type VIII Group B Streptococcus capsular polysaccharide, the structure of which is {L-Rhap(beta 1-->4)-D-Glcp(beta 1-->4) [Neu5Ac(alpha 2-->3)]-D-Galp(beta 1-->4}(n). The synthesis presented three significant synthetic challenges namely: the L-Rhap(beta 1-->4)-D-Glcp bond, the Neu5Ac(alpha 2-->3)-D-Galp bond and 3,4-D-Galp branching. The L-Rhap bond was constructed in 60% yield (alpha:beta l:1.2) using 4-O-acetyl-2, 3-di-O-benzoyl-alpha-L-rhamnopyranosyl bromide 6 as donor, silver silicate as promotor and 6-O-benzyl-2,3-di-O-benzoyl-1-thio-beta-D-glucopyranoside as acceptor to yield disaccharide 18. The Neu5Ac(alpha 2-->3) linkage was synthesized in 66% yield using methyl [phenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-nonulopyranosid]onate as donor and triol 2-(trimethylsilyl) ethyl 6-O-benzyl-beta-D-galactopyranoside as acceptor to give disaccharide 21. The 3,4-D-Galp branching was achieved by regioselective glycosylation of disaccharide diol 21 by disaccharide 18 in 28% yield to give protected tetrasaccharide 22. Tetrasaccharide 22 was deprotected to give as its 2-(trimethylsilyl)ethyl glycoside the title compound 1a. In addition the 2-(trimethylsilyl)ethyl group was cleaved and the tetrasaccharide coupled by glycosylation (via tetrasaccharide trichloroacetimidate) to a linker suitable for conjugation.