NOVEL SYNTHESIS OF MEVINOLIN-RELATED COMPOUNDS - LARGE-SCALE PREPARATION OF HMG-COA REDUCTASE INHIBITOR L-679,336

A novel synthetic route to a mevinolin-related HMG-CoA reductase inhibitor L-679,336 is described. The key features of the synthesis are a diastereoselective osmium tetraoxide catalyzed dihydroxylation reaction and a highly selective, phosphorus-mediated, pinacol-type rearrangement to give ketone 6. In situ multinuclear NMR experiments were used to gain a detailed understanding of the pinacol step. The above route was used for multikilogram preparation of the title compound. Also described are Lewis acid catalyzed rearrangement reactions of epoxide intermediates 4 and 5, as well as the intramolecular hydrosilylation reaction of deacylated olefinic substrates 17 and 18.