Synthesis of an Aminooxy Derivative of the Tetrasaccharide Repeating Unit of Streptococcus dysgalactiae 2023 Polysaccharide for a PS A1 Conjugate Vaccine.

Abstract

A highly efficient and stereocontrolled synthesis of an aminooxy derivative of the tetrasaccharide repeating unit of a rhamnose-rich polysaccharide isolated from the cell envelop of bovine mastitis Streptococcus dysgalactiae 2023 is reported for the first time. The synthesis was accomplished utilizing a stereoselective and convergent [2 + 2] glycosylation strategy inclusive of a disaccharide Schmidt donor and an inclusive rhamnose disaccharide acceptor. The synthetic aminooxy tetrasaccharide was conjugated to T-cell stimulating immunogen PS A1 from Bacteroides fragilis ATCC 25285/NCTC 9343 via a physiologically stable oxime linkage to furnish the first semisynthetic bacterial-based immunogen construct targeting S. dysgalactiae 2023. The synthetic tetrasaccharide was assembled in 19 steps with a ∼5.0% overall yield.