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

摘要

Based on the combined use of dimethyl-formamide (DMF) modulation and neighboring group participation, three iterative one-pot α-glyco-sylation methods, i.e., one-pot (α,α)-, one-pot (β,α)-, and one-pot (α,β)-glycosylations, were developed. These methods are applicable to a range of thiogly-cosyl donors, confer stereocontrol in α-/β-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-α(1→3)-D-Glc-α(1→3)-L-Rha trisaccharide unit of the cell wall component in Streptococcus pneumoniae, and the d-Glc-α(1→2)-D-Glc-α(1→3)-d-G1c trisaccharide terminus of the N-linked glycan precursor. Confirmation of the anomeric configurations of these oligosaccharides is evidenced by ~1H, ~(13)C, ~(13)C-non-proton decoupling, and heteronuclear correlation 2D NMR experiments. Global deprotection of selected oligosaccharide targets is illustrated.