Synthesis of a spacer-containing nonasaccharide fragment of Streptococcus pneumoniae 19F capsular polysaccharide

Abstract

The nonasaccharide 1, representing three repeating units of the capsular polysaccharide from Streptococcus pneumoniae 19F, has been synthesized. The synthetic strategy is to first synthesize, by an AB + C route, trisaccharide derivative 14, having O-benzyl groups as persistent, and 1-O-allyl and 4″-O-acetyl groups as temporary, protecting groups. Then, specific replacement of the 1-O-allyl group with an α-H-phosphonate monoester gives trisaccharide 17, which is coupled to a spacer. The obtained derivative 18 is then extended from the 4″ end in a stepwise fashion to give compound 20, using trisaccharide 17 and solution-phase H-phosphonate chemistry. Finally, removal of the persistent O-protecting groups gives the nonasaccharide 1.