Synthesis of the Aminoglucuronic Acid Glycans from the Capsular Polysaccharide of Staphylococcus aureus type 2

Abstract

The escalating antibiotic resistance of Staphylococcus aureus has made glycoconjugate vaccines targeting its surface polysaccharides a highly promising strategy for preventing staphylococcal infections. However, the development of a type 2-specific S. aureus vaccine has been hindered by the limited accessibility of its unique aminoglucuronic acid glycans. Efficient assembly of complex aminoglucuronic acid glycans with diverse amino modifications was described by employing the photolabile o-nitrobenzyloxycarbonyl (oNBC) and hydrogenolysis-labile trichloroacetyl (TCA) groups as orthogonal amine-protecting groups. A late-stage oxidation step was utilized to simultaneously convert multiple primary hydroxyl groups of the amino-oligosaccharide chains to carboxylate groups. This approach provided access to a series of aminoglucuronic acid antigens of varying lengths and N-functionalization patterns, serving as the basis for the rational development of a glycoconjugate vaccine against S. aureus type 2.