Synthetic Study of PI-88 Analogue Based on O-Glycosidation Technique of 1-exo-Methylenesugars

Abstract

We have recently reported that the acid-catalyzed O-glycosidation of 1-exo-methylenesugars afforded 1-C-methyl-α-glycosides in a highly α-stereoselective manner. Applying this method to the oligosaccharide-synthesis, we envisioned the synthesis of 1-C-methyl-substituted analogue of PI-88, which is a potent heparanase inhibitor. After a survey of several catalysts, it was found that methanesulfonic acid promoted the reaction without the cleavage of acid sensitive MPM ether existing in the sugar unit. Therefore, we succeeded in the synthesis of O-protected pentasaccharide by the sequence of O-glycosidation/MPM-deprotection processes.