Total synthesis and glycosidase inhibition of broussonetine I and J(2)

J Org Chem. 2013 Aug 16;78(16):7896-902. doi: 10.1021/jo4010553. Epub 2013 Jul 29.

Abstract

The first total synthesis of both broussonetine I and J2 together with their enantiomers have been accomplished via the same synthetic route through 18 and 16 steps in excellent overall yields (18% and 19%, respectively), starting from R-glyceraldehyde. Broussonetine I was found to be a potent inhibitor of β-glucosidase (IC50 = 2.9 μM), while ent-broussonetine I and ent-broussonetine J2 were found to be potent inhibitors of α-glucosidase (IC50 = 0.33 and 0.53 μM, respectively).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspergillus niger / enzymology
  • Cattle
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glycoside Hydrolases / antagonists & inhibitors*
  • Glycoside Hydrolases / metabolism
  • Helix, Snails / enzymology
  • Imino Sugars / chemical synthesis
  • Imino Sugars / chemistry
  • Imino Sugars / pharmacology*
  • Molecular Conformation
  • Plants / enzymology
  • Rats
  • Saccharomyces cerevisiae / enzymology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Imino Sugars
  • broussonetine I
  • broussonetine J
  • Glycoside Hydrolases