Synthesis of fragments of salmonella typhi capsular polysaccharide

We will report on the synthesis of oligomers of Salmonella enterica serovar Typhi (often called S. Typhi) capsular polysaccharide (CPS). S. Typhi is a motile Gram-negative bacterium, whose CPS (often referred to as Vi antigen) is an anionic polymer composed of α-(1-4)-linked N-acetyl galactosaminuronic acid repeating units predominantly O-acetylated at position 3. We developed a strategy based on versatile intermediates enabling chain elongation either by iterative single monomer attachment or by faster and more flexible approach using disaccharide donors. All these intermediates were obtained from commercially available D-galactosamine hydrochloride. Glycosylation reactions were carried out using N-phenyl-trifluoroacetimidates as glycosyl donors, yielding stereoselectively the desired α product. Late stage C-6 oxidation was done by a Dess-Martin/Pinnick oxidation. Finally, a suitable linker was installed at C-1 of the reducing end in order to facilitate the subsequent conjugation to protein carrier and/or multivalent scaffolds.