Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783585127680442368 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7506938 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American
Chemical Society |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT grimmchristopher oxygenfreeregioselectivebiocatalyticdemethylationofmethylphenylethersviamethyltransferemployingveratrolodemethylase AT lazzarottomattia oxygenfreeregioselectivebiocatalyticdemethylationofmethylphenylethersviamethyltransferemployingveratrolodemethylase AT pompeisimona oxygenfreeregioselectivebiocatalyticdemethylationofmethylphenylethersviamethyltransferemployingveratrolodemethylase AT schichlerjohanna oxygenfreeregioselectivebiocatalyticdemethylationofmethylphenylethersviamethyltransferemployingveratrolodemethylase AT richternina oxygenfreeregioselectivebiocatalyticdemethylationofmethylphenylethersviamethyltransferemployingveratrolodemethylase AT farnbergerjudithe oxygenfreeregioselectivebiocatalyticdemethylationofmethylphenylethersviamethyltransferemployingveratrolodemethylase AT fuchsmichael oxygenfreeregioselectivebiocatalyticdemethylationofmethylphenylethersviamethyltransferemployingveratrolodemethylase AT kroutilwolfgang oxygenfreeregioselectivebiocatalyticdemethylationofmethylphenylethersviamethyltransferemployingveratrolodemethylase |