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

Angew Chem Int Ed Engl. 2023 Jan 26;62(5):e202214759. doi: 10.1002/anie.202214759. Epub 2022 Dec 22.

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 N-heterocyclic compounds. Scalable biocatalytic oxygenations (27 preparative examples, ca. 100 mg scale) have been developed across a wide range of substrates, including alkyl pyridines, bicyclic N-heterocycles and indoles. H2 O2 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.

Keywords: Biocatalysis; Cytochromes P450; Oxygenation; Peroxygenase; Unspecific Peroxygenase (UPO).

MeSH terms

  • Biocatalysis
  • Catalysis
  • Mixed Function Oxygenases* / metabolism

Substances

  • peroxygenase
  • Mixed Function Oxygenases