Synthesis of monofluorinated isofagomine analogues and evaluation as glycosidase inhibitors

The straightforward synthesis of monofluorinated isofagomine analogues 1-3 was described. The synthetic strategy featured that the chiral carbon center bearing fluorine atom was constructed stereoselectively via silicon-induced Reformatskii-Claisen rearrangement of allyl bromofluoroacetate. These compounds were tested for inhibition of five glycosidases. The 3S,4R,5R isomer 3 has been found to be a potent inhibitor against beta-glucosidase from almonds with K(i) value of 11.9 mu M. (C) 2011 Elsevier B.V. All rights reserved.