- First systematic chiral syntheses of two pairs of enantiomers with 3,5-dihydroxyheptenoic acid chain, associated with a potent synthetic statin NK-104
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First systematic chiral syntheses of two pairs of enantiomers with 3,5-dihydroxyheptenoic acid chain, associated with a potent synthetic statin NK-104 are reported. A pair of syn diol isomers (NK-104 and its enantiomer) was obtained efficiently by diastereomeric resolution. The synthesis of a pair of anti diol isomers (3-epimer and 5-epimer) was accomplished effectively by the asymmetric aldol reaction followed by anti stereoselective reduction as key steps. Their purity determinations were effected by chiral HPLC analysis.
- Suzuki, Mikio,Yanagawa, Yoshinobu,Iwasaki, Hiroshi,Kanda, Hiroyasu,Yanagihara, Kazufumi,Matsumoto, Hiroo,Ohara, Yoshio,Yazaki, Yukari,Sakoda, Ryozo
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p. 2977 - 2982
(2007/10/03)
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- Stereoselective reduction of β,δ-diketo esters. A novel strategy for the synthesis of artificial HMG-CoA reductase inhibitors
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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.
- Hiyama,Reddy,Minami,Hanamoto
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p. 350 - 363
(2007/10/02)
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