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 (alpha- and beta-D-glucosidases, alpha-D-mannosidase and alpha-L-fucosidase). Inhibition studies indicate notably that the polyhydroxylated azepanes are inhibitors of glycosidases, with K-i in the micromolar range. (C) 1997 Elsevier Science Ltd.