Synthesis of 3-substituted isofagomine analogues using an unusual syn hydrogenation reaction

Abstract

Isofagomine (3,4-dihydroxy-5-(hydroxymethyl)piperidine, 1) and analogues are found to be strong inhibitors of glycosidases, and are therefore of potential interest in treatment of various disorders. Starting from cheap and readily available materials we have developed a new diastereoselective synthesis of 3,4,5-trisubstituted piperidines of the isofagomine type. (±)-3-Amino-3-deoxyisofagomine (2) and a series of 11 closely related structures were synthesized via three key intermediates 5–7 in relatively few and high yielding steps. The biological activity of compounds 2, 8–18 was investigated towards several enzymes, and new inhibitors of glycosidases were found.