Iterative One-Pot alpha-Glycosylation Strategy: Application to Oligosaccharide Synthesis

Abstract

Based on the combined use of dimethylformamide (DMF) modulation and neighboring group participation, three iterative one-pot a-glycosylation methods, i.e., one-pot (a,a)-, one-pot (beta,a)-, and one-pot (a,beta)-glycosylations, were developed. These methods are applicable to a range of thioglycosyl donors, confer stereocontrol in a-/beta-glycosidic bond formation, and thus provide for rapid access to oligosaccharides with various permutations of anomeric configurations. The utility of these one-pot glycosylation methods is demonstrated in the synthesis of eight non-natural and natural oligosaccharide targets, including the core 1 serine conjugate, core 8 serine conjugate, the D-Gal-a(1?3)-D-Glc-a(1?3)-L-Rha trisaccharide unit of the cell wall component in Streptococcus pneumoniae, and the D-Glc-a(1?2)-D-Glc-a(1?3)-D-Glc trisaccharide terminus of the N-linked glycan precursor. Confirmation of the anomeric configurations of these oligosaccharides is evidenced by 1H, 13C, 13C-non-proton decoupling, and heteronuclear correlation 2D NMR experiments. Global deprotection of selected oligosaccharide targets is illustrated.