Novel Synthesis of Mevinolin-Related Compounds. Large-Scale Preparation of HMG-CoA Reductase Inhibitor L-679,336

Article abstract of DOI:10.1021/jo00011a022

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.