Aziridines as a structural motif to conformational restriction of azasugars

Abstract

In order to investigate the hypothesis that the glycosidase inhibitor isofagomine was bound to α-or β-glucosidase in a ^1,4B conformation, a number of bicyclic aziridines that adopt the ^1,4B or B_1,4 conformations were synthesised and investigated. (1R)-2-endo,3-exo-2,3-Dihydroxy-4-endo-4-hydroxymethyl-6-azabicyclo[3.1.0]hexane (5) and its N-methyl and N-benzyl analogues and (1S)-2-exo-3-endo-2,3-dihydroxy-4-endo-4-hydroxymethyl-6-azabicyclo[3.1.0]hexane (6) were synthesised. The aziridines 5 and 6 were found to be weak or not inhibitors of α-glucosidase, β-glucosidase and α-fucosidase.