Galacturonic acid lactones in the synthesis of all trisaccharide repeating units of the zwitterionic polysaccharide Sp1

Abstract

A modular approach toward the synthesis of all possible trimer repeating units of the type 1 capsular polysaccharide of Streptococcus pneumonia, Sp1, is described. This zwitterionic polysaccharide is built up from trisaccharide repeats, which in turn are composed of two galacturonic acid monomers and a 2,4,6-trideoxy-4-amino-2-acetamido-D-galactose moiety. All monomeric constituents are linked through cis-glycosidic bonds. To overcome the difficulty associated with the efficient stereoselective introduction of the R-galacturonic acid bonds, we have employed galacturonic acid-[3,6]-lactone building blocks. Not only did these building blocks perform well when used as donor galactosides, they were also shown to be reactive acceptor glycosides when equipped with a free hydroxyl function. All three frame-shifted trimer repeats were constructed via highly stereoselective glycosylation reactions, with one exception. The epimeric mixture of trisaccharides, formed in the nonselective glycosylation event, could be readily separated after global deprotection using high performance anion exchange chromatography (HPEAC).© 2011 American Chemical Society.