A sterically directed site- and stereoselective O-glycosylation of of tert-butyl gensitate has been developed. The excellent site-selectivity originates from the large steric hindrance of tert-butyl group. This glycosylation protocol, in conjunction with subsequent convenient deprotections, provides an efficient access to plant-derived natural bioactive gentisic acid 5-O-glycosides, which are otherwise difficult to prepare.

Abstract

Gentisic acid 5-O-glycosides are a large family of plant-derived natural products that show a wide spectrum of bioactivities. However, their chemical synthesis is highly challenging, due to the site-selectivity issue that is quite difficult to tackle. Previous synthetic routes are very rare and suffer from inefficiency arising from tedious protection and deprotection manipulations. Herein, we report a sterically directed site- and stereoselective O-glycosylation of tert-butyl gensitate. The large steric hindrance of tert-butyl group plays an extremely important role in delivering excellent site- and stereoselectivities. This glycosylation protocol, followed by convenient and mild deprotections, allows for easy access to natural and bioactive gentisic acid 5-O-glycosides.