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Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol-O-demethylase

[Image: see text] The cleavage of aryl methyl ethers is a common reaction in chemistry requiring rather harsh conditions; consequently, it is prone to undesired reactions and lacks regioselectivity. Nevertheless, O-demethylation of aryl methyl ethers is a tool to valorize natural and pharmaceutical...

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Autores principales: Grimm, Christopher, Lazzarotto, Mattia, Pompei, Simona, Schichler, Johanna, Richter, Nina, Farnberger, Judith E., Fuchs, Michael, Kroutil, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506938/
https://www.ncbi.nlm.nih.gov/pubmed/32974079
http://dx.doi.org/10.1021/acscatal.0c02790
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author Grimm, Christopher
Lazzarotto, Mattia
Pompei, Simona
Schichler, Johanna
Richter, Nina
Farnberger, Judith E.
Fuchs, Michael
Kroutil, Wolfgang
author_facet Grimm, Christopher
Lazzarotto, Mattia
Pompei, Simona
Schichler, Johanna
Richter, Nina
Farnberger, Judith E.
Fuchs, Michael
Kroutil, Wolfgang
author_sort Grimm, Christopher
collection PubMed
description [Image: see text] The cleavage of aryl methyl ethers is a common reaction in chemistry requiring rather harsh conditions; consequently, it is prone to undesired reactions and lacks regioselectivity. Nevertheless, O-demethylation of aryl methyl ethers is a tool to valorize natural and pharmaceutical compounds by deprotecting reactive hydroxyl moieties. Various oxidative enzymes are known to catalyze this reaction at the expense of molecular oxygen, which may lead in the case of phenols/catechols to undesired side reactions (e.g., oxidation, polymerization). Here an oxygen-independent demethylation via methyl transfer is presented employing a cobalamin-dependent veratrol-O-demethylase (vdmB). The biocatalytic demethylation transforms a variety of aryl methyl ethers with two functional methoxy moieties either in 1,2-position or in 1,3-position. Biocatalytic reactions enabled, for instance, the regioselective monodemethylation of substituted 3,4-dimethoxy phenol as well as the monodemethylation of 1,3,5-trimethoxybenzene. The methyltransferase vdmB was also successfully applied for the regioselective demethylation of natural compounds such as papaverine and rac-yatein. The approach presented here represents an alternative to chemical and enzymatic demethylation concepts and allows performing regioselective demethylation in the absence of oxygen under mild conditions, representing a valuable extension of the synthetic repertoire to modify pharmaceuticals and diversify natural products.
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spelling pubmed-75069382020-09-22 Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol-O-demethylase Grimm, Christopher Lazzarotto, Mattia Pompei, Simona Schichler, Johanna Richter, Nina Farnberger, Judith E. Fuchs, Michael Kroutil, Wolfgang ACS Catal [Image: see text] The cleavage of aryl methyl ethers is a common reaction in chemistry requiring rather harsh conditions; consequently, it is prone to undesired reactions and lacks regioselectivity. Nevertheless, O-demethylation of aryl methyl ethers is a tool to valorize natural and pharmaceutical compounds by deprotecting reactive hydroxyl moieties. Various oxidative enzymes are known to catalyze this reaction at the expense of molecular oxygen, which may lead in the case of phenols/catechols to undesired side reactions (e.g., oxidation, polymerization). Here an oxygen-independent demethylation via methyl transfer is presented employing a cobalamin-dependent veratrol-O-demethylase (vdmB). The biocatalytic demethylation transforms a variety of aryl methyl ethers with two functional methoxy moieties either in 1,2-position or in 1,3-position. Biocatalytic reactions enabled, for instance, the regioselective monodemethylation of substituted 3,4-dimethoxy phenol as well as the monodemethylation of 1,3,5-trimethoxybenzene. The methyltransferase vdmB was also successfully applied for the regioselective demethylation of natural compounds such as papaverine and rac-yatein. The approach presented here represents an alternative to chemical and enzymatic demethylation concepts and allows performing regioselective demethylation in the absence of oxygen under mild conditions, representing a valuable extension of the synthetic repertoire to modify pharmaceuticals and diversify natural products. American Chemical Society 2020-08-31 2020-09-18 /pmc/articles/PMC7506938/ /pubmed/32974079 http://dx.doi.org/10.1021/acscatal.0c02790 Text en Copyright © 2020 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Grimm, Christopher
Lazzarotto, Mattia
Pompei, Simona
Schichler, Johanna
Richter, Nina
Farnberger, Judith E.
Fuchs, Michael
Kroutil, Wolfgang
Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol-O-demethylase
title Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol-O-demethylase
title_full Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol-O-demethylase
title_fullStr Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol-O-demethylase
title_full_unstemmed Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol-O-demethylase
title_short Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol-O-demethylase
title_sort oxygen-free regioselective biocatalytic demethylation of methyl-phenyl ethers via methyltransfer employing veratrol-o-demethylase
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506938/
https://www.ncbi.nlm.nih.gov/pubmed/32974079
http://dx.doi.org/10.1021/acscatal.0c02790
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