温和な条件下優れた活性を示し, 高い立体・位置・官能基選択性で反応が進行, かつ, 化学触媒に比べ製造速度が格段に速い酵素を一層活用することを目標に, 化学－酵素複合合成を検討した。具体的成果として, 位置選択性を活用し, フェノール性生物活性物質アルテピリンC, セリノン, アストリンギンを合成した。反応媒体として水を使わず, 酸・塩基の影響を受けにくいエステル交換は光学分割にも有用であり, (R)-3-ヒドロキシ-N-メチルピペリジンを, ラセミ体の速度論的光学分割により調製した。さらに, 遠隔不斉認識能を明らかにし, キラル誘導分析試薬であるMNBカルボン酸メチルエステルの両鏡像体も合成した。
Complementary and synergistic utilization of enzyme-catalyzed reactions and chemical transformation was studied, toward the efficient synthesis of complex target molecules involving valuable natural and unnatural products. The achievements are shown below. Lipase-catalyzed transesterification proceeded with specific site-selectivity contrasting to chemical transformations, and the syntheses of selinone and astringin, artepillin C became successful. It was revealed that the transesterification under non-aqueous conditions was advantageous for the substrates which are labile to water and/or prone to protonation under aqueous conditions. The preparation of highly enantiomerically pure (R)-3-hydroxy-N-methylpiperidine by the lipase-catalyzed kinetic resolution of corresponding racemate was established. The synthesis of enantiomers of NMB carboxylic acid was also successful, by discriminating he stereochemistry of remote chiral center in a primary acetate, as the key step.
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