Asymmetric Synthesis of Optically Pure Pharmacologically Relevant Amines Employing ω-Transaminases

Authors

  • Dominik Koszelewski,

    1. Department of Chemistry, Organic and Bioorganic Chemistry, University of Graz, Heinrichstrasse 28, A-8010 Graz, Austria, Fax: (+43)-316-380-9840
    2. Research Centre Applied Biocatalysis, Graz, Austria
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  • Iván Lavandera,

    1. Department of Chemistry, Organic and Bioorganic Chemistry, University of Graz, Heinrichstrasse 28, A-8010 Graz, Austria, Fax: (+43)-316-380-9840
    2. Research Centre Applied Biocatalysis, Graz, Austria
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  • Dorina Clay,

    1. Department of Chemistry, Organic and Bioorganic Chemistry, University of Graz, Heinrichstrasse 28, A-8010 Graz, Austria, Fax: (+43)-316-380-9840
    2. Research Centre Applied Biocatalysis, Graz, Austria
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  • David Rozzell,

    1. Codexis, Inc., Redwood City, California, USA
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  • Wolfgang Kroutil

    1. Department of Chemistry, Organic and Bioorganic Chemistry, University of Graz, Heinrichstrasse 28, A-8010 Graz, Austria, Fax: (+43)-316-380-9840
    2. Research Centre Applied Biocatalysis, Graz, Austria
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Abstract

Various ω-transaminases were tested for the synthesis of enantiomerically pure amines from the corresponding ketones employing D- or L-alanine as amino donor and lactate dehydrogenase to remove the side-product pyruvate to shift the unfavourable reaction equilibrium to the product side. Both enantiomers, (R)- and (S)-amines, could be prepared with up to 99% ee and >99% conversions within 24 h at 50 mM substrate concentration. The activity and stereoselectivity of the amination reaction depended on the ω-transaminase and substrate employed; furthermore the co-solvent significantly influenced both the stereoselectivity and activity of the transaminases. Best results were obtained by employing ATA-117 to obtain the (R)-enantiomer and ATA-113 or ATA-103 to access the (S)-enantiomer with 15% v v−1 DMSO.

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