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 4a, 4b and 4c, 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 α-D-xylopentodialdose followed by hydrogenolysis to afford the triol 5. Selective amidation of the α- and β -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 β-glycosidases with IC₅₀ values in the micro molar range. Compound 4c showed excellent potency against glycosidases and human salivary amylase.