The spirocyclopropyl moiety as a methyl surrogate in the structure of l-fucosidase and l-rhamnosidase inhibitors

Bioorg Med Chem. 2009 Dec 1;17(23):8020-6. doi: 10.1016/j.bmc.2009.10.010. Epub 2009 Oct 12.

Abstract

Nitrogen-in-the-ring analogues of l-fucose and l-rhamnose were prepared, which feature a spirocyclopropyl moiety in place of the methyl group of the natural sugar. The synthetic route involved a titanium-mediated aminocyclopropanation of a glycononitrile as the key step. Four new spirocyclopropyl iminosugar analogues were generated, which displayed some activity towards l-fucosidase and l-rhamnosidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclopropanes / chemical synthesis*
  • Cyclopropanes / chemistry
  • Cyclopropanes / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Fucose / analogs & derivatives*
  • Fucose / chemical synthesis
  • Fucose / chemistry
  • Fucose / pharmacology
  • Glycoside Hydrolases / antagonists & inhibitors
  • Glycoside Hydrolases / metabolism
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Optical Rotation
  • Rhamnose / analogs & derivatives*
  • Rhamnose / chemical synthesis
  • Rhamnose / chemistry
  • Rhamnose / pharmacology
  • Spectrometry, Mass, Electrospray Ionization
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology
  • alpha-L-Fucosidase / antagonists & inhibitors
  • alpha-L-Fucosidase / metabolism

Substances

  • Cyclopropanes
  • Enzyme Inhibitors
  • Spiro Compounds
  • Fucose
  • Glycoside Hydrolases
  • alpha-L-rhamnosidase
  • alpha-L-Fucosidase
  • Rhamnose