Synthesis and glycosidase inhibitory activity of aminocyclitols with a C6- or a C7-ring

The synthesis of carbasugars and various aminocyclitols, related to voglibose and acarbose used in the treatment of non-insulino-dependant diabetes, is described from C2-symmetrical bis-epoxides derived from d-mannitol. The methodology involves two key steps: a domino alkylation–cyclization with 2-lithio-1,3-dithiane derivatives, and reduction or reductive amination with a primary amine. These compounds have been evaluated as inhibitors of several glycosidases, and this study indicates notably that the l-ido or d-manno 1-aminocycloheptane-3,4,5,6-tetrol are inhibitors of α-d-glucosidase with Ki in the micromolar range.