Synthesis and evaluation of the glycosidase inhibitory activity of 5-hydroxy substituted isofagomine analogues

Abstract

An efficient strategy for the synthesis of 5-hydroxy substituted isofagomine analogues and , having both -CH2OH/CH3 and -OH functionality at the C-5 position, and evaluation of their inhibitory potency is reported. The synthetic methodology involves the aldol-Cannizzaro reaction of easily available alpha-d-xylopentodialdose followed by hydrogenolysis to afford the triol . Selective amidation of the alpha- and beta-hydroxymethyl group at C-4, deprotection of the 1,2-acetonide group and hydrogenation gave the target molecules, which were found to be potent against beta-glycosidases with IC50 values in the micro molar range. Compound showed excellent potency against glycosidases and human salivary amylase.