Synthesis of new nitrogen analogues of salacinol and deoxynojirimycin and their evaluation as glycosidase inhibitors

J Org Chem. 2006 Feb 3;71(3):894-902. doi: 10.1021/jo0517388.

Abstract

The synthesis of two enantiomerically pure iminosugars, analogues of 1-L-deoxynojirimycin (l-DNJ) and 1-D-deoxymannojirimycin (DMJ), was achieved using cyclic sulfate substituted isoxazoline derivatives. The piperidine ring was formed via the reduction of an isoxazoline into an amine which underwent a spontaneous intramolecular cyclization by reaction with the cyclic sulfate moiety. The nucleophilic attack of these two trisubstituted piperidines and morpholine on L- and D-erythritol-1,3-cyclic sulfates gave six new nitrogen analogues of salacinol. The inhibitory properties of the synthesized salacinol analogues were evaluated on several commercial glycosidases.

MeSH terms

  • 1-Deoxynojirimycin / chemical synthesis
  • 1-Deoxynojirimycin / chemistry*
  • Alkylation
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glycoside Hydrolases / antagonists & inhibitors*
  • Glycoside Hydrolases / metabolism
  • Hydroxylation
  • Molecular Structure
  • Morpholines / chemistry
  • Nitrogen / chemistry*
  • Sugar Alcohols / chemical synthesis
  • Sugar Alcohols / chemistry*
  • Sulfates / chemical synthesis
  • Sulfates / chemistry*

Substances

  • Enzyme Inhibitors
  • Morpholines
  • Sugar Alcohols
  • Sulfates
  • salacinol
  • 1-Deoxynojirimycin
  • morpholine
  • Glycoside Hydrolases
  • Nitrogen