PRACTICAL SYNTHESIS OF CHIRAL SYNTHONS FOR THE PREPARATION OF HMG-COAREDUCTASE INHIBITORS

A practical procedure for the enantioselective preparation of opticall y pure (R)- and (S)-monomethyl esters of 3-[(tert-butyldimethylsilyl)o xy]pentanedioic acid has been developed by diastereoselective ring-ope ning of 3-[(tert-butyldimethylsilyl)oxy]pentanedioic anhydride 5 by be nzyl (R)- and (S)-mandelate, respectively. These half-esters afforded chiral Wittig reagent 2 and Horner-Wadsworth-Emmons (HWE) reagent 1 ef ficiently which have been proved to be useful in the synthesis of HMG- CoA reductase inhibitors. The method is applied to the synthesis of th e (R)-3-methylglutaric acid, monomethyl ester.