Preparative-Scale Biocatalytic Oxygenation of N-Heterocycles with a Lyophilized Peroxygenase Catalyst

Gideon James Grogan; Balazs Pogranyi; Tamara Mielke; Alba Diaz-Rodriguez; Jared Cartwright; William Paul Unsworth

doi:10.1002/anie.202214759

Preparative-Scale Biocatalytic Oxygenation of N-Heterocycles with a Lyophilized Peroxygenase Catalyst

Gideon James Grogan, Balazs Pogranyi, Tamara Mielke, Alba Diaz-Rodriguez, Jared Cartwright, William Paul Unsworth

Chemistry

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

Abstract

A lyophilized preparation of an unspecific peroxygenase
variant from Agrocybe aegerita (rAaeUPO-PaDa-I-H) is a highly
effective catalyst for the oxygenation of a diverse range of Nheterocyclic
compounds. Scalable biocatalytic oxygenations (27
preparative examples, ≈100 mgs scale) have been developed across
a wide range of substrates, including alkyl pyridines, bicyclic Nheterocycles
and indoles. H2O2 is the only stoichiometric oxidant
needed, without auxiliary electron transport proteins, which is key to
the practicality of the method. Reaction outcomes can be altered
depending on whether hydrogen peroxide was delivered by syringe
pump or through in situ generation using an alcohol oxidase from
Pichia pastoris (PpAOX) and methanol as a co-substrate. Good
synthetic yields (up to 84%), regioselectivity and enantioselectivity (up
to 99% ee) were observed in some cases, highlighting the promise of
UPOs as practical, versatile and scalable oxygenation biocatalysts.

Original language	English
Article number	e202214759
Journal	Angewandte Chemie International Edition
Volume	62
Issue number	5
Early online date	1 Dec 2022
DOIs	https://doi.org/10.1002/anie.202214759
Publication status	E-pub ahead of print - 1 Dec 2022

Bibliographical note

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10.1002/anie.202214759Licence: CC BY

Angew Chem Int Ed - 2022 - Pogr nyi - Preparative‐Scale Biocatalytic Oxygenation of N‐Heterocycles with a Lyophilized
© 2022 The Authors.
Final published version, 2.18 MBLicence: CC BY

Cite this

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title = "Preparative-Scale Biocatalytic Oxygenation of N-Heterocycles with a Lyophilized Peroxygenase Catalyst",

abstract = "A lyophilized preparation of an unspecific peroxygenasevariant from Agrocybe aegerita (rAaeUPO-PaDa-I-H) is a highlyeffective catalyst for the oxygenation of a diverse range of Nheterocycliccompounds. Scalable biocatalytic oxygenations (27preparative examples, ≈100 mgs scale) have been developed acrossa wide range of substrates, including alkyl pyridines, bicyclic Nheterocyclesand indoles. H2O2 is the only stoichiometric oxidantneeded, without auxiliary electron transport proteins, which is key tothe practicality of the method. Reaction outcomes can be altereddepending on whether hydrogen peroxide was delivered by syringepump or through in situ generation using an alcohol oxidase fromPichia pastoris (PpAOX) and methanol as a co-substrate. Goodsynthetic yields (up to 84%), regioselectivity and enantioselectivity (upto 99% ee) were observed in some cases, highlighting the promise ofUPOs as practical, versatile and scalable oxygenation biocatalysts.",

author = "Grogan, {Gideon James} and Balazs Pogranyi and Tamara Mielke and Alba Diaz-Rodriguez and Jared Cartwright and Unsworth, {William Paul}",

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T1 - Preparative-Scale Biocatalytic Oxygenation of N-Heterocycles with a Lyophilized Peroxygenase Catalyst

AU - Grogan, Gideon James

AU - Pogranyi, Balazs

AU - Mielke, Tamara

AU - Diaz-Rodriguez, Alba

AU - Cartwright, Jared

AU - Unsworth, William Paul

PY - 2022/12/1

Y1 - 2022/12/1

N2 - A lyophilized preparation of an unspecific peroxygenasevariant from Agrocybe aegerita (rAaeUPO-PaDa-I-H) is a highlyeffective catalyst for the oxygenation of a diverse range of Nheterocycliccompounds. Scalable biocatalytic oxygenations (27preparative examples, ≈100 mgs scale) have been developed acrossa wide range of substrates, including alkyl pyridines, bicyclic Nheterocyclesand indoles. H2O2 is the only stoichiometric oxidantneeded, without auxiliary electron transport proteins, which is key tothe practicality of the method. Reaction outcomes can be altereddepending on whether hydrogen peroxide was delivered by syringepump or through in situ generation using an alcohol oxidase fromPichia pastoris (PpAOX) and methanol as a co-substrate. Goodsynthetic yields (up to 84%), regioselectivity and enantioselectivity (upto 99% ee) were observed in some cases, highlighting the promise ofUPOs as practical, versatile and scalable oxygenation biocatalysts.

AB - A lyophilized preparation of an unspecific peroxygenasevariant from Agrocybe aegerita (rAaeUPO-PaDa-I-H) is a highlyeffective catalyst for the oxygenation of a diverse range of Nheterocycliccompounds. Scalable biocatalytic oxygenations (27preparative examples, ≈100 mgs scale) have been developed acrossa wide range of substrates, including alkyl pyridines, bicyclic Nheterocyclesand indoles. H2O2 is the only stoichiometric oxidantneeded, without auxiliary electron transport proteins, which is key tothe practicality of the method. Reaction outcomes can be altereddepending on whether hydrogen peroxide was delivered by syringepump or through in situ generation using an alcohol oxidase fromPichia pastoris (PpAOX) and methanol as a co-substrate. Goodsynthetic yields (up to 84%), regioselectivity and enantioselectivity (upto 99% ee) were observed in some cases, highlighting the promise ofUPOs as practical, versatile and scalable oxygenation biocatalysts.

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