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 β-glucosidase from almonds with Ki value of 11.9 μM.

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► The chiral carbon center bearing fluorine atom was constructed stereoselectively via silicon-induced Reformatskii–Claisen rearrangement of allyl bromofluoroacetate.
► Three monofluorinated isofagomine analogues were designed and prepared.
► The biological evaluation showed that compound 3 was a potent inhibitor of β-glucosidase from almonds.