Schizostatin, a novel squalene synthase inhibitor produced by the mushroom, Schizophyllum commune. II. Structure elucidation and total synthesis

J Antibiot (Tokyo). 1996 Jul;49(7):624-30. doi: 10.7164/antibiotics.49.624.

Abstract

Schizostatin (1) has been isolated as a potent and selective inhibitor of squalene synthase. Its structure has been determined using spectroscopic methods: the compound is shown to be a diterpenoid which has a trans-dicarboxylic acid moiety. Total synthesis of schizostatin (1) was achieved by the highly regio- and stereoselective coupling reaction of an allylic bromide with a barium reagent. The Z-isomer 16 was also prepared using the stereoselective syn-addition of an organocopper reagent to acetylenedicarboxylate.

MeSH terms

  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Farnesyl-Diphosphate Farnesyltransferase / antagonists & inhibitors*
  • Fatty Acids / chemical synthesis
  • Fatty Acids / chemistry*
  • Fumarates / chemical synthesis
  • Fumarates / chemistry*
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Schizophyllum / metabolism
  • Spectrometry, Mass, Fast Atom Bombardment

Substances

  • Enzyme Inhibitors
  • Fatty Acids
  • Fumarates
  • schizostatin
  • Farnesyl-Diphosphate Farnesyltransferase