Synthesis and glycosidase inhibition potency of all-trans substituted 1-C-perfluoroalkyl iminosugars

Abstract

Synthetic analogues of the naturally occurring iminosugar homoDMDP, which feature a perfluoroalkyl group at the pseudo-anomeric position, have been synthesized from the corresponding sugar-derived cyclic aldonitrone. The new fluorinated iminosugars as well as homoDMDP and its 6-deoxy counterpart were evaluated for their inhibitory activity against a panel of glycosidases. While the replacement of the (1′,2′)-dihydroxyethyl substituent of homoDMDP with –C4F9 proved detrimental for enzyme binding, introduction of a –C3F7 moiety tuned the inhibitory activity spectrum selectively towards α-fucosidase and α-glucosidase from yeast.