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Stereoselective Biocatalytic Synthesis of (S)-2-Hydroxy-2-Methylbutyric Acid via Substrate Engineering by Using “Thio-Disguised” Precursors and Oxynitrilase Catalysis

Authors

  • Martin H. Fechter Dr.,

    1. Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 16, 8010 Graz, Austria, Fax: (+43) 316 873 8740
    2. Research Centre Applied Biocatalysis, Petersgasse 14, 8010 Graz, Austria
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  • Karl Gruber Prof.,

    1. Institute of Chemistry, Karl-Franzens-Universität, Heinrichstrasse 28, 8010 Graz, Austria
    2. Research Centre Applied Biocatalysis, Petersgasse 14, 8010 Graz, Austria
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  • Manuela Avi Dipl.-Ing.,

    1. Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 16, 8010 Graz, Austria, Fax: (+43) 316 873 8740
    2. Research Centre Applied Biocatalysis, Petersgasse 14, 8010 Graz, Austria
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  • Wolfgang Skranc Dr.,

    1. DSM Fine Chemicals Austria, St. Peter-Strasse 25, 4021 Linz, Austria
    2. Research Centre Applied Biocatalysis, Petersgasse 14, 8010 Graz, Austria
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  • Christian Schuster Dr.,

    1. DSM Fine Chemicals Austria, St. Peter-Strasse 25, 4021 Linz, Austria
    2. Research Centre Applied Biocatalysis, Petersgasse 14, 8010 Graz, Austria
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  • Peter Pöchlauer Dr.,

    1. DSM Fine Chemicals Austria, St. Peter-Strasse 25, 4021 Linz, Austria
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  • Kurt O. Klepp Prof.,

    1. Institute of Inorganic Chemistry, University of Linz, Altenbergerstrasse 69, 4040 Linz, Austria
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  • Herfried Griengl Prof.

    1. Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 16, 8010 Graz, Austria, Fax: (+43) 316 873 8740
    2. Research Centre Applied Biocatalysis, Petersgasse 14, 8010 Graz, Austria
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Abstract

3-Tetrahydrothiophenone (4) and 4-phenylthiobutan-2-one (7) were used as masked 2-butanone equivalents to give the corresponding cyanohydrins 5 (79 % yield, 91 % ee) and 8 (95 % yield, 96 % ee) in an enzymatic cyanohydrin reaction applying the hydroxynitrile lyase (HNL) from Hevea brasiliensis. After hydrolysis and desulphurisation the desired intermediate (S)-2-hydroxy-2-methylbutyric acid (10) was obtained with 99 % ee. Interestingly, when applying (R)-selective HNL from Prunus amygdalus again the (S)-cyanohydrin 5 was formed (62 % ee). The absolute configuration of 5 was verified by crystal structure determination of the corresponding hydrolysis derived carboxylate. The fact that both enzymes yield the same enantiomer was analysed and interpreted by molecular modelling calculations.

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