Synthesis of azasugars as potent inhibitors of glycosidases

A series of enantiomerically pure azasugars (2,5-dideoxy-2,5-imino- d-mannitol, 1-deoxynojirimycin, 1-deoxymannojirimycin, and related compounds) was synthesized from d-mannitol via aminoheterocyclization of C 2-symmetric bis-epoxides and subsequently followed by ring isomerization in few cases. These compounds have been evaluated as inhibitors of several glycosidases (α- and β- d-glucosidases, α- d-mannosidase and α- l-fucosidase). Inhibition studies indicate notably that the polyhydroxylated azepanes are inhibitors of glycosidases, with K 1 in the micromolar range. A series of enantiomerically pure azasugars with a pyrrolidine, piperidine, or an azepane framework was synthesized from d-mannitol. Biological studies indicate, notably, that the polyhydroxylated azepanes are inhibitors of glycosidases with the K i values in the low micromolar range.