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

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
Article numbere202214759
JournalAngewandte Chemie International Edition
Issue number5
Early online date1 Dec 2022
Publication statusE-pub ahead of print - 1 Dec 2022

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