Generation of homochiral aziridinium ion intermediates derived from 2,3-epoxy amines: regiospecific nucleophilic trapping with nitrogen nucleophiles. Application in the synthesis of novel morpholinosphingolipid analogues with potential glucosylceramide synthase inhibitory activity

Abstract

The Lewis acid induced rearrangement of 2,3-epoxy amines into the corresponding 2-trimethylsilyloxymethylaziridinium ions is described. Such intermediates have been characterised by ¹H NMR spectroscopy, and react with nitrogen nucleophiles regiospecifically to form 1-substituted 2,3-amino alcohols in good to excellent yields and with full stereochemical control. This methodology has been applied to the synthesis of a potential inhibitor of glucosylceramide synthase, a promising target for cancer chemotherapy.