General synthesis and biological evaluation of α-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-α-C-glycosides)

A general synthesis of α-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-α-C-glycosides) by ring-opening reactions of an aziridine with various heteroatomic nucleophiles, including thiol, amine, alcohol, carboxylate and phosphate, is described. The nine-step reaction sequence proceeded in an overall yield of 14–28% from tri-O-benzyl-D-glucal. Biological evaluation of α-1-C-substituted derivatives of fagomine, of the 2-deoxy analog of α-homonojirimycin 19 and its 1,N-anhydro derivative 22 as glycosidase inhibitors is reported. The glycosyl phosphate mimetic 15k was found to display no inhibitory activity towards glycogen phosphorylase b and phosphoglucomutase.

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