C=C-Ene-Reductases Reduce the C=N Bond of Oximes

Stefan Velikogne; Willem B Breukelaar; Florian Hamm; Ronald A Glabonjat; Wolfgang Kroutil

doi:10.1021/acscatal.0c03755

C=C-Ene-Reductases Reduce the C=N Bond of Oximes

ACS Catal. 2020 Nov 20;10(22):13377-13382. doi: 10.1021/acscatal.0c03755. Epub 2020 Nov 3.

Authors

Stefan Velikogne¹, Willem B Breukelaar¹, Florian Hamm¹, Ronald A Glabonjat², Wolfgang Kroutil^{1

3

4}

Affiliations

¹ Institute of Chemistry, University of Graz, NAWI Graz, Heinrichstrasse 28, 8010 Graz, Austria.
² Institute of Chemistry, University of Graz, NAWI Graz, Universitätsplatz 1, 8010 Graz, Austria.
³ Field of Excellence BioHealth, University of Graz, 8010 Graz, Austria.
⁴ BioTechMed Graz, 8010 Graz, Austria.

Abstract

Although enzymes have been found for many reactions, there are still transformations for which no enzyme is known. For instance, not a single defined enzyme has been described for the reduction of the C=N bond of an oxime, only whole organisms. Such an enzymatic reduction of an oxime may give access to (chiral) amines. By serendipity, we found that the oxime moiety adjacent to a ketone as well as an ester group can be reduced by ene-reductases (ERs) to an intermediate amino group. ERs are well-known enzymes for the reduction of activated alkenes, as of α,β-unsaturated ketones. For the specific substrate used here, the amine intermediate spontaneously reacts further to tetrasubstituted pyrazines. This reduction reaction represents an unexpected promiscuous activity of ERs expanding the toolkit of transformations using enzymes.