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

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.