Intramolecular aglycon delivery and its application to stereoselective synthesis of glycans

Abstract

1,2-cis Glycosidic linkages are prevalent in natural glycans. Although key factors that control stereoselectivity of glycosylation have been largely understood, stereoselective synthesis of 1,2-cis glycosides is potentially problematic. To achieve exclusive formation of desired isomer, approaches based on intramolecular aglycon delivery TAD are of special promise. In the last two decades, various mixed acetal linkages and a number of glycosyl donor moieties have been making much progress to develop novel TAD strategies, mainly based on formation of the acetal linkages. The methodology toward the strereoselective 1,2-cis glycosylation using naphthylmethyl NAP ether-mediated LAD has been developed. Namely, 2-0-NAP protected donor was cleanly converted to the mixed acetal upon oxidative activation with DDQ. Subsequent activation of thioglycosidic linkage initiated the rearrangement of an aglycon from mixed acetal moiety to give a desired 1,2-cis glycoside. Stereospecific constructions of various 1,2-cis linkages, which are not only β-mannopyranoside but also other linkages such as β-L-rhamno-, α-glucopyrano- and β- arabinofurano-sides, were achieved through NAP-LAD. This methodology was successfully applied to the synthesis of various fragments of natural glycans.