Convergent Synthesis of Oligosaccharide Fragments Corresponding to the Cell Wall O-Polysaccharide of Salmonella enterica O53

Abstract

Conventional glycoconjugate vaccines are prepared with polysaccharides isolated from bacterial fermentation, an approach with some significant drawbacks such as handling of live bacterial strains, the presence of biological impurities, and inter-batch variations in oligosaccharide epitope structure. However, it has been shown in many cases that a synthetic fragment of appropriate structure conjugated to a protein can be an effective vaccine that circumvents the shortcomings of using full-length oligosaccharides. The development of synthetic strategies to prepare glycoconjugate derivatives against pathogenic bacterial strains is therefore of great interest. Oligosaccharide fragments corresponding to the repeat unit of the cell wall O-antigen of Salmonella enterica strain O53 were synthesized in good yield. Sequential and block glycosylation strategies were used for the synthesis of the target compounds. A number of recently developed reaction conditions were used in the synthetic strategy. A one-pot reaction scheme was also developed for the multiple glycosylation steps. The stereoselective outcomes of all glycosylation reactions were very good.