Synthetic Zwitterionic Streptococcus pneumoniae Type 1 Oligosaccharides Carrying Labile O‐Acetyl Esters

Abstract

AbstractWe herein report the first total synthesis of the Streptococcus pneumoniae serotype 1 (Sp1) oligosaccharide, a unique zwitterionic capsular polysaccharide carrying labile O‐acetyl esters. The target oligosaccharides, featuring rare α‐2,4‐diamino‐2,4,6‐trideoxy galactose (AAT) and α‐galacturonic acids, were assembled up to the 9‐mer level, in a highly stereoselective manner using trisaccharide building blocks. The lability of the O‐acetyl esters imposed a careful deprotection scheme to prevent migration and hydrolysis. The migration was investigated in detail at various pD values using NMR spectroscopy, to show that migration and hydrolysis of the C‐3‐O‐acetyl esters readily takes place under neutral conditions. Structural investigation showed the oligomers to adopt a right‐handed helical structure with the acetyl esters exposed on the periphery of the helix in close proximity of the neighboring AAT residues, thereby imposing conformational restrictions on the AATα1‐4GalA(3OAc) glycosidic linkages, supporting the helical shape of the polysaccharide, that has been proposed to be critical for its unique biological activity.