STEREOSELECTIVE REDUCTION OF BETA,DELTA-DIKETO ESTERS - A NOVEL STRATEGY FOR THE SYNTHESIS OF ARTIFICIAL HMG-COA REDUCTASE INHIBITORS

Condensation of N-methoxy-N-methyl amides with the dianions of acetoacetates gives in good yields beta,delta-diketo esters, which are reduced with Et(2)BOMe-NaBH4 in tetrahydrofuran-methanol highly selectively to give syn-beta,delta-dihydroxy esters in one step. Similarly, the beta,delta-diketo esters of the Taber's chiral alcohol or its enantiomer respectively are reduced to give syn,S-dihydroxy esters of moderate enantiomeric excess. Higher diastereo- and enantioselectivity were achieved by reduction of the beta,delta-diketo esters of the Taber's chiral alcohol or its enantiomer successively with diisobutylalane and with Et(2)BOMe-NaBH4. The resulting syn-diol esters were hydrolyzed and lactonized to give various types of beta-hydroxy-delta-lactones commonly found in artificial HMG-CoA reductase inhibitors.