Stereoselective reduction of β,δ-diketo esters. A novel strategy for the synthesis of artificial HMG-CoA reductase inhibitors

Article abstract of DOI:10.1246/bcsj.68.350

Condensation of N-methoxy-N-methyl amides with the dianions of acetoacetates gives in good yields β,δ-diketo esters, which are reduced with Et₂BOMe-NaBH₄ in tetrahydrofuran-methanol highly selectively to give syn-β,δ-dihydroxy esters in one step. Similarly, the β,δ-diketo esters of the Taber's chiral alcohol or its enantiomer respectively are reduced to give syn-β,δ-dihydroxy esters of moderate enantiomeric excess. Higher diastereo- and enantioselectivity were achieved by reduction of the β,δ-diketo esters of the Taber's chiral alcohol or its enantiomer successively with diisobutylalane and with Et₂BOMe-NaBH₄. The resulting syn-diol esters were hydrolyzed and lactonized to give various types of β-hydroxy-δ-lactones commonly found in artificial HMG-CoA reductase inhibitors.