Mechanism of Chemical Glycosylation: Focus on the Mode of Activation and Departure of Anomeric Leaving Groups

Abstract

Many glycosyl donors used in chemical glycosylation are too stable to undergo spontaneous glycosylation. Hence, the first key step of practically every glycosylation reaction is the activation of the leaving group that usually takes place via its interaction with a promoter/activator or, more rarely, a catalyst. The focus of this review is the first key step of glycosylation with the emphasis on the modes by which the leaving groups are activated and departed. Studies wherein the exact nature of the activation process has been reliably elucidated are still scarce. Therefore, this review particularly details the mechanistic studies wherein the mode of activation was proven either by characterizing the activated intermediates or by isolation of the departed leaving group–activator adducts.

Keywords:

• Glycosylation
• Leaving group
• Activation
• Oligosaccharides
• Reaction mechanism

ACKNOWLEDGMENTS

The authors thank the National Science Foundation (Award CHE-1058112) and National Institute of General Medical Studies (Award GM077170) for providing generous support for their efforts to study the reaction mechanism and applying this knowledge to the development of new methods and strategies for expeditious oligosaccharide synthesis.