An alternative high yielding and highly stereoselective method for preparing an α-Neu5NAc-(2,6)-d-GalN3 building block suitable for further glycosylation

This paper deals with new approaches to α-Neu5NAc-(2,6)-d-GalN3 building blocks, suitable as glycosylation donors. The major improvement, by comparison with the results of the literature, lies in the glycosylation step of a new d-galactosamine acceptor (tert-butyldimethylsilyl 3-O-acetyl-2-azido-2-deoxy-β-d-galactopyranoside) with O-methyl-S-[methyl(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-non-2-ulopyranosyl)onate] dithiocarbonate as the N-acetylneuraminic acid donor. The reaction affords the expected disaccharide in high yield (85%) and a complete α-Neu5NAc stereoselectivity. A subsequent oxidation step, eliminating the glycal by-product allows an easier purification. Afterwards, the tert-butyldimethylsilyl disaccharide can be transformed into a donor, after cleavage of the anomeric group in smooth conditions.