An Anti-Clostridium difficile Vaccine: Chemical Synthesis of the Pentasaccharide Repeating Unit of Polysaccharide PS-I

Clostridium difficile is a Gram-positive bacterium that is the most common cause of hospital-associated and antimicrobial-associated diarrhea in humans. Monteiro and co-workers have discovered that C. difficile expresses three cell-surface polysaccharides, named PS-I, PS-II and PS-III. Interestingly, PS-I was determined to be present in a ribotype 027 strain, the ribotype responsible for recent deadly outbreaks worldwide. In this work, the total chemical synthesis of the PS-I pentasaccharide with a linker molecule by a linear synthesis strategy from four monosaccharide building blocks is described: α-L-Rhap-(1→3)-β-D-Glcp-(1→4)-α-D-Glcp-(1→2)-α-D-Glcp-(1→O(CH2)5NH