Diverse Library of 5a-Substituted Carba-Glucosamines

Abstract

Carba-sugars─carbohydrate mimics in which the ring oxygen is replaced by a methylene group─are carbohydrate analogues of natural or synthetic origin that can have important biological functions. Especially, carba-aminosugars and glycosides containing carba-aminosugars are potent antibiotics. Furthermore, they have been shown to induce the self-cleavage reaction of the glmS riboswitch and thereby inhibit the ability of bacteria to synthesize glucosamine-6-phosphate, which is required to build up the bacterial cell wall. We report the synthesis of a library of 20 carba-glucosamine derivatives with various substituents at the carba-position including amines, alkyl, alkoxy, and aryloxy derivatives, fluorine derivatives, glycosylated derivatives, and a cyclopropane derivative. The compounds were obtained in an efficient way starting from late-stage synthetic intermediates of an earlier-developed synthesis of carba-substituted carba-glucosamines. All carba-glucosamine mimics were tested for their antibacterial properties against Bacillus subtilis, and some of them displayed promising activities in a filter disk assay.