Total asymmetric synthesis of (-)-conduramine B-1 and of its enantiomer. N-Benzyl derivatives of conduramine B-1 are beta-glucosidase inhibitors

Bioorg Med Chem Lett. 2005 Jun 15;15(12):3071-5. doi: 10.1016/j.bmcl.2005.04.023.

Abstract

The 'naked sugars' (+)- and (-)-7-oxabicyclo[2.2.1]hept-5-en-2-one have been converted into (-)-conduramine B-1 ((-)-3) and its enantiomer (+)-3, respectively. They have been condensed with a variety of aldehydes in the presence of NaBH(OAc)(3). The N-substituted derivatives 4 and ent-4 so-obtained have been tested against two alpha-glucosidases, two amyloglucosidases, two beta-glucosidases and one beta-xylosidase for their inhibitory activities. Although (-)-3 and (+)-3 do not inhibit any of these enzymes at 1mM concentration, N-benzylated derivatives of (-)-conduramine B-1 are selective and competitive inhibitors of beta-glucosidases with K(i) in low micromolecular range.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus niger / enzymology
  • Bacteria, Anaerobic / enzymology
  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / pharmacology
  • Cellulases / antagonists & inhibitors*
  • Cyclohexenes
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Glycoside Hydrolase Inhibitors*
  • Hexosamines / chemical synthesis*
  • Hexosamines / chemistry
  • Hexosamines / pharmacology
  • Molecular Structure
  • Prunus / enzymology
  • Saccharomyces cerevisiae / enzymology
  • Stereoisomerism
  • Structure-Activity Relationship
  • Xylosidases / antagonists & inhibitors*

Substances

  • Bridged Bicyclo Compounds
  • Cyclohexenes
  • Enzyme Inhibitors
  • Glycoside Hydrolase Inhibitors
  • Hexosamines
  • valienamine
  • Cellulases
  • Xylosidases
  • exo-1,4-beta-D-xylosidase