Accelerated O-Glycosylation under Frozen Conditions and Its Application to the Synthesis of Complex Glycans

Abstract

Enormous rate acceleration was observed when O-glycosylation was conducted in p-xylene below its freezing point, as determined by comparative studies under both frozen and unfrozen conditions. The mechanistic implications of stereoselectivity on glycosylation under frozen systems were also investigated. Examination of the effects of various factors, such as solvent, concentration, anomeric configuration and protective groups of the donor, revealed that the stereoselectivity was affected by concentration both in liquid and in frozen conditions. The rate acceleration in frozen solvent was caused by the highly concentrated environments found therein. The substrate concentration under frozen conditions was estimated to be about 50 times higher than that before freezing. This manuscript also summarizes the application of this technique to the synthesis of complex glycans as well as bioactive molecules.