C‐Branched Imino Sugars: Synthesis and Biological Relevance

Abstract

Only few naturally occurring pyrrolizidine imino sugars possess a geminal‐hydroxyhydroxymethyl group. In search for more potent and selective inhibitors of carbohydrate processing enzymes, organic chemists took inspiration from this uncommon feature. The presence of such a group formally results from either i) a shift of the hydroxymethyl group of the imino sugar toward an adjacent hydroxylated position or ii) the addition of a second hydroxymethyl group on a tertiary alcohol. Five‐, six‐, seven‐membered ring imino sugars and bicyclic imino sugars embedding this structural feature were thus prepared by innovative synthetic strategies. Some of these derivatives are very potent and selective inhibitors of glycosidases. Moreover, several C‐branched imino sugars proved recently to act as corrector of F508del‐CTFR and open the way for the development of derivatives relevant in the context of cystic fibrosis.