Efficient synthesis of (+)-1,8,8a-tri-epi-swainsonine, (+)-1,2-di-epi-lentiginosine, (+)-9a-epi-homocastanospermine and (−)-9-deoxy-9a-epi-homocastanospermine from a d-glucose-derived aziridine carboxylate, and study of their glycosidase inhibitory activities

Abstract

The utility of a D-glucose-derived aziridine carboxylate was demonstrated for the synthesis of polyhydroxylated quinolizidine and indolizidine alkaloids. The chemoselective reduction of 1 followed by two-carbon homologation by the Wittig reaction afforded γ,δ-aziridino-α,β-unsaturated ester9, which on regioselective nucleophilic aziridine ring opening either by using water as a nucleophile or hydrogenation afforded δ-lactams 11/16—true synthons for the synthesis of four structurally different iminosugars, namely quinolizidine alkaloids5b/5c, swainsonine 6b and lentiginosine 7b analogues. Glycosidase inhibitory activities of these iminosugars were investigated.