One-pot Chemoenzymatic Synthesis of Chiral 1,3-Diols Using an Enantioselective Aldol Reaction with Chiral Zn2+ Complex Catalysts and Enzymatic Reduction Using Oxidoreductases with Cofactor Regeneration

Authors

  • Shotaro Sonoike,

    1. Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510 (Japan), Fax: (+81) 4-7121-3670
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  • Toshinari Itakura,

    1. Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510 (Japan), Fax: (+81) 4-7121-3670
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  • Dr. Masanori Kitamura,

    1. Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510 (Japan), Fax: (+81) 4-7121-3670
    2. Center for Technologies against Cancer, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510 (Japan)
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  • Prof. Shin Aoki

    Corresponding author
    1. Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510 (Japan), Fax: (+81) 4-7121-3670
    2. Center for Technologies against Cancer, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510 (Japan)
    • Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510 (Japan), Fax: (+81) 4-7121-3670

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Abstract

We previously reported on enantioselective aldol reactions of acetone and some aldehydes catalyzed by chiral Zn2+ complexes of L-prolyl-pendant [12]aneN4 (L-ZnL1) and L-valyl-pendant [12]aneN4 (L-ZnL2) in aqueous solution. Here, we report on the one-pot chemoenzymatic synthesis of chiral 1,3-diols in an aqueous solvent system at room temperature by a combination of enantioselective aldol reactions catalyzed by Zn2+ complexes of L- and D-phenylalanyl-pendant [12]aneN4 (L-ZnL3 and D-ZnL3) and the successive enantioselective reduction of the aldol products using oxidoreductases with the regeneration of the NADH (reduced form of nicotinamine adenine dinucleotide) cofactor. The findings indicate that all four stereoisomers of 1,3-diols can be produced by appropriate selection of a chiral Zn2+-complex and an oxidoreductase commercially available from the “Chiralscreen OH” kit.

Abstract

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