Synthesis of PSI Oligosaccharide for the Development of Total Synthetic Vaccine against Clostridium difficile

Clostridium difficile causes serious nosocomial diarrhea in humans. In particular, C. difficile ribotype 027 strain, which is more virulent in nature, is associated with higher mortality rates. To prevent disease caused by C. difficile, capsular polysaccharides such as PSI, PSII, and PSIII from the outermost protective layer of C. difficile bacterium are good targets in the development of vaccine against C. difficile. In this study, we report for the first time an efficient synthesis of phosphorylated PSI oligosaccharide and its derivatives in various lengths. We have also developed a one-pot strategy for the synthesis of a pentasaccharide repeating unit and used this approach to successfully synthesize the protected pentasaccharides in the gram scale.