SYNTHESIS OF AZASUGARS AS POTENT INHIBITORS OF GLYCOSIDASES

A series of enantiomerically pure azasugars (2,5-dideoxy-2,5-imino-D-m annitol, 1-deoxynojirimycin, 1-deoxymannojirimycin, and related compou nds) was synthesized from D-mannitol via aminoheterocyclization of C-2 -symmetric bis-epoxides and subsequently followed by ring isomerizatio n in few cases. These compounds have been evaluated as inhibitors of s everal glycosidases (alpha- and beta-D-glucosidases, alpha-D-mannosida se and alpha-L-fucosidase). Inhibition studies indicate notably that t he polyhydroxylated azepanes are inhibitors of glycosidases, with K-i in the micromolar range. (C) 1997 Elsevier Science Ltd.