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

An efficient strategy for the synthesis of 5-hydroxy substituted isofagomine analogues 4a, 4b and 4c, having both -CH<SUB>2</SUB>OH/CH<SUB>3</SUB> 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 &#945;-D-xylopentodialdose followed by hydrogenolysis to afford the triol 5. Selective amidation of the &#945;- and &#946; -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 &#946;-glycosidases with IC<SUB>50 </SUB>values in the micro molar range. Compound 4c showed excellent potency against glycosidases and human salivary amylase