Schizostatin, a Novel Squalene Synthase Inhibitor Produced by the Mushroom, Schizophyllum commune

II. Structure Elucidation and Total Synthesis

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 stereo selective coupling reaction of an allylic bromide with a barium reagent. The Z-isomer 16 was also prepared using the stereo selective syn-addition of an organocopper reagent to acetylenedicarboxylate.