Highly efficient preparation of tumor antigen-containing glycopeptide building blocks from novel pentenyl glycosides Original Research Article

O-Glycosylated amino acids containing the tumor-associated T(Tf)-antigen (β-d-Gal-(1→3)-α-d-GalNAc) disaccharide unit were conveniently synthesized in seven steps starting from d-galactose via an n-pentenyl glycoside (NPG) building block. Azidonitration of 3,4,6-tri-O-acetyl-d-galactal, followed by nitrate displacement with simultaneous acetate hydrolysis with sodium 4-penten-1-oxide, afforded n-pentenyl 2-deoxy-2-azidogalactoside (3) in near quantitative yield. Subsequent high-yielding transformations resulted in the synthesis of the key glycosyl donor n-pentenyl β-disaccharide 5 that was employed for the stereospecific preparation of glycosyl amino acids via NIS-promoted glycosylations with serine or threonine acceptors. The surprising utility of the reaction of sodium 4-penten-1-oxide with anomeric nitrates encouraged the detailed exploration of the action of a variety of nucleophiles on anomeric nitrates for the synthesis of useful 2-azido glycosyl donors directly from the ‘classic’ Lemieux azidonitration product of protected galactals. This expedient synthesis (28% overall yield from 1 to 7a) that makes use of heretofore rarely exploited pentenyl 2′-azidoglycosides, should be a valuable entry in the armamentarium of routes to biologically relevant glycopeptides in both mono- and multivalent forms.