SCHIZOSTATIN, A NOVEL SQUALENE SYNTHASE INHIBITOR PRODUCED BY THE MUSHROOM, SCHIZOPHYLLUM-COMMUNE .2. 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 spectro scopic methods: the compound is shown to be a diterpenoid which has a trans-dicarboxylic acid moiety. Total synthesis of schizostatin (1) wa s achieved by the highly regio- and stereoselective coupling reaction of an allylic bromide with a barium reagent. The 2-isomer 16 was also prepared using the stereoselective syn-addition of an organocopper rea gent to acetylenedicarboxylate.