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.

Keywords: Glycosidase inhibition; Iminosugar; Perfluoroalkyl chain; homoDMDP.