We 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.
Keywords: Acyl Migration; Bacterial Oligosaccharides; Glycosylation; Helical Structure; Stereoselectivity.
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