Toward a General Glycosylation Strategy: Exploring the Dual Functions of Acyl Group Direction in Various Nucleophilic Environments

A universal glycosylation strategy could significantly simplify glycoside synthesis. One approach to achieving this goal is through acyl group stereodirecting participation for the corresponding 1,2-, 1,3-, 1,4-, or 1,6-trans glycosylation; how-ever, this approach had been challenging for glycosidic bonds that require distal equatorial-acyl group direction. We have developed an approach in weakly nucleophilic environments for selective 1,4-trans glycosylation directed by the equato-rial-4-O-acyl group. Here, we explored this condition in other distal acyl groups and found, besides stereodirecting partic-ipation, acyl groups also mediated hydrogen bonding between acyl groups and alcohols. The latter showed a diverse ef-fect and classified the acyl group direction into axial and equatorial categories. Corresponding glycosylation conditions were distinguished as guidance for acyl group direction from either category. Hence, the acyl group direction may serve as a general glycosylation strategy.