Expanding the Scope of Alcohol Dehydrogenases towards Bulkier Substrates: Stereo- and Enantiopreference for α,α-Dihalogenated Ketones

Authors

  • Kinga Kędziora,

    1. Department of Organic and Inorganic Chemistry, Instituto Universitario de Biotecnología de Asturias, University of Oviedo, Avenida Julián Clavería s/n, 33006 Oviedo (Spain)
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  • Dr. Fabricio R. Bisogno,

    1. Department of Organic and Inorganic Chemistry, Instituto Universitario de Biotecnología de Asturias, University of Oviedo, Avenida Julián Clavería s/n, 33006 Oviedo (Spain)
    2. INFIQC-CONICET, Dpto. de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, CP 5000, Córdoba (Argentina)
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  • Dr. Iván Lavandera,

    1. Department of Organic and Inorganic Chemistry, Instituto Universitario de Biotecnología de Asturias, University of Oviedo, Avenida Julián Clavería s/n, 33006 Oviedo (Spain)
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  • Dr. Vicente Gotor-Fernández,

    1. Department of Organic and Inorganic Chemistry, Instituto Universitario de Biotecnología de Asturias, University of Oviedo, Avenida Julián Clavería s/n, 33006 Oviedo (Spain)
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  • Dr. Jose Montejo-Bernardo,

    1. Departamento de Química Física y Analítica, Universidad de Oviedo, Avenida Julián Clavería s/n, Oviedo 33006 (Spain)
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  • Prof. Santiago García-Granda,

    1. Departamento de Química Física y Analítica, Universidad de Oviedo, Avenida Julián Clavería s/n, Oviedo 33006 (Spain)
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  • Prof. Wolfgang Kroutil,

    1. Department of Chemistry, Organic and Bioorganic Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz (Austria)
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  • Prof. Vicente Gotor

    Corresponding author
    1. Department of Organic and Inorganic Chemistry, Instituto Universitario de Biotecnología de Asturias, University of Oviedo, Avenida Julián Clavería s/n, 33006 Oviedo (Spain)
    • Department of Organic and Inorganic Chemistry, Instituto Universitario de Biotecnología de Asturias, University of Oviedo, Avenida Julián Clavería s/n, 33006 Oviedo (Spain)

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Abstract

Alcohol dehydrogenases (ADHs) were identified as suitable enzymes for the reduction of the corresponding α,α-dihalogenated ketones, obtaining optically pure β,β-dichloro- or β,β-dibromohydrins with excellent conversions and enantiomeric excess. Among the different biocatalysts tested, ADHs from Rhodococcus ruber (ADH-A), Ralstonia sp. (RasADH), Lactobacillus brevis (LBADH), and PR2ADH proved to be the most efficient ones in terms of activity and stereoselectivity. In a further study, two racemic α-substituted ketones, namely α-bromo- α-chloro- and α-chloro-α-fluoroacetophenone were investigated to obtain one of the four possible diastereoisomers through a dynamic kinetic process. In the case of the brominated derivative, only the (1R)-enantiomer was obtained by using ADH-A, although with moderate diastereomeric excess (>99 % ee, 63 % de), whereas the fluorinated ketone exhibited a lower stereoselectivity (up to 45 % de).

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