Multistep Oxidase–Lyase Reactions: Synthesis of Optically Active 2-Hydroxyketones by Using Biobased Aliphatic Alcohols

Authors

  • Dr. María Pérez-Sánchez,

    1. Institut für Technische und Makromolekulare Chemie (ITMC), RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany), Fax: (+49) 241-8022177
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  • Christoph R. Müller,

    1. Institut für Technische und Makromolekulare Chemie (ITMC), RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany), Fax: (+49) 241-8022177
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  • Dr. Pablo Domínguez de María

    Corresponding author
    1. Institut für Technische und Makromolekulare Chemie (ITMC), RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany), Fax: (+49) 241-8022177
    • Institut für Technische und Makromolekulare Chemie (ITMC), RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany), Fax: (+49) 241-8022177
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Abstract

Enzymatic multistep reactions are presently an important research field, from which integrated and efficient synthetic protocols can be created, accompanied by a diminished waste formation (avoiding downstream units operations). This article explores the benzaldehyde lyase (BAL) catalyzed crossed carboligation of benzaldehyde with different aliphatic aldehydes to afford optically active α-hydroxyketones. To this end, different biobased aliphatic alcohols were in situ oxidized to aldehydes by oxidase from Hansenula sp. and subsequently carboligated with benzaldehyde by BAL in the same reactor system. For short nonbranched aliphatic alcohols, moderate to high conversions in carboligations (15–99 %) with excellent enantioselectivities (98–99 %, R), were achieved. Both enzymes also exhibited activities at high concentrations of benzaldehyde (up to 200 mM) and with butanol as cosolvent, albeit at the cost of lower conversions, presumably owing to kinetic reasons. After needed optimization of the biocatalyst (e.g., through genetic evolution, whole-cell setup) and the process setup (e.g., stepwise addition of substrates, reaction time), the herein reported concept might provide promising entries in the field of asymmetric synthesis, delivering useful building blocks starting from biobased materials, and in an integrative manner.

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