The Reactivity of α-Fluoroketones with PLP Dependent Enzymes: Transaminases as Hydrodefluorinases

Marina Garcia-Ramos; Anibal Cuetos; Wolfgang Kroutil; Gideon James Grogan; Iván Lavandera

doi:10.1002/cctc.202100901

The Reactivity of α-Fluoroketones with PLP Dependent Enzymes: Transaminases as Hydrodefluorinases

Marina Garcia-Ramos, Anibal Cuetos, Wolfgang Kroutil, Gideon James Grogan, Iván Lavandera

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

A chemical method for the treatment of harmful halogenated compounds that has recently become of interest is the reductive dehalogenation of carbon–halogen bonds. In the case of a fluorine atom, this process is called hydrodefluorination. While many transition metal-based approaches now exist to reductively defluorinate aromatic fluoroarenes, the cleavage of C–F bonds in aliphatic compounds is not so well-developed. Here we propose a biocatalytic approach exploiting a promiscuous activity exhibited by transaminases (TAs). Hence, a series of α-fluoroketones have been defluorinated with excellent conversions using Chromobacterium violaceum and Arthrobacter sp. TAs under mild conditions and in aqueous medium, using a stoichiometric amount of an amine (e.g. 2-propylamine) as reagent and formally releasing its oxidized form (e.g. acetone), with ammonia and hydrogen fluoride as by-products. It is also demonstrated that this process can be performed in a regio- or stereoselective fashion.

Original language	English
Pages (from-to)	3967-3972
Journal	ChemCatChem
Volume	13
Issue number	18
Early online date	6 Aug 2021
DOIs	https://doi.org/10.1002/cctc.202100901
Publication status	Published - 17 Sept 2022

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cctc.202100901
© 2021 The Authors. ChemCatChem published by Wiley-VCH GmbH.
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Cite this

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title = "The Reactivity of α-Fluoroketones with PLP Dependent Enzymes: Transaminases as Hydrodefluorinases",

abstract = "A chemical method for the treatment of harmful halogenated compounds that has recently become of interest is the reductive dehalogenation of carbon–halogen bonds. In the case of a fluorine atom, this process is called hydrodefluorination. While many transition metal-based approaches now exist to reductively defluorinate aromatic fluoroarenes, the cleavage of C–F bonds in aliphatic compounds is not so well-developed. Here we propose a biocatalytic approach exploiting a promiscuous activity exhibited by transaminases (TAs). Hence, a series of α-fluoroketones have been defluorinated with excellent conversions using Chromobacterium violaceum and Arthrobacter sp. TAs under mild conditions and in aqueous medium, using a stoichiometric amount of an amine (e.g. 2-propylamine) as reagent and formally releasing its oxidized form (e.g. acetone), with ammonia and hydrogen fluoride as by-products. It is also demonstrated that this process can be performed in a regio- or stereoselective fashion.",

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T1 - The Reactivity of α-Fluoroketones with PLP Dependent Enzymes: Transaminases as Hydrodefluorinases

AU - Garcia-Ramos, Marina

AU - Cuetos, Anibal

AU - Kroutil, Wolfgang

AU - Grogan, Gideon James

AU - Lavandera, Iván

PY - 2022/9/17

Y1 - 2022/9/17

N2 - A chemical method for the treatment of harmful halogenated compounds that has recently become of interest is the reductive dehalogenation of carbon–halogen bonds. In the case of a fluorine atom, this process is called hydrodefluorination. While many transition metal-based approaches now exist to reductively defluorinate aromatic fluoroarenes, the cleavage of C–F bonds in aliphatic compounds is not so well-developed. Here we propose a biocatalytic approach exploiting a promiscuous activity exhibited by transaminases (TAs). Hence, a series of α-fluoroketones have been defluorinated with excellent conversions using Chromobacterium violaceum and Arthrobacter sp. TAs under mild conditions and in aqueous medium, using a stoichiometric amount of an amine (e.g. 2-propylamine) as reagent and formally releasing its oxidized form (e.g. acetone), with ammonia and hydrogen fluoride as by-products. It is also demonstrated that this process can be performed in a regio- or stereoselective fashion.

AB - A chemical method for the treatment of harmful halogenated compounds that has recently become of interest is the reductive dehalogenation of carbon–halogen bonds. In the case of a fluorine atom, this process is called hydrodefluorination. While many transition metal-based approaches now exist to reductively defluorinate aromatic fluoroarenes, the cleavage of C–F bonds in aliphatic compounds is not so well-developed. Here we propose a biocatalytic approach exploiting a promiscuous activity exhibited by transaminases (TAs). Hence, a series of α-fluoroketones have been defluorinated with excellent conversions using Chromobacterium violaceum and Arthrobacter sp. TAs under mild conditions and in aqueous medium, using a stoichiometric amount of an amine (e.g. 2-propylamine) as reagent and formally releasing its oxidized form (e.g. acetone), with ammonia and hydrogen fluoride as by-products. It is also demonstrated that this process can be performed in a regio- or stereoselective fashion.

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