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

Isofagomine (3,4-dihydroxy-5-(hydroxymethyl)piperidine, 1) and analogues ar e found to be strong inhibitors of glycosidases, and are therefore of poten tial interest in treatment of various disorders. Starting from cheap and re adily available materials we have developed a new diastereoselective synthe sis of 3,4,5-trisubstituted piperidines of the isofagomine type. (+/-)-3-Am ino-3-deoxyisofagomine (2) and a series of 11 closely related structures we re synthesized via three key intermediates 5-7 in relatively few and high y ielding steps. The biological activity of compounds 2, 8-18 was investigate d towards several enzymes, and new inhibitors of glycosidases were found.