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

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

Stefan Velikogne  1 , Willem B Breukelaar  1 , Florian Hamm  1 , Ronald A Glabonjat  2 , Wolfgang Kroutil  1   3   4
Affiliations

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

Stefan Velikogne et al. ACS Catal. .

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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Reductive Transformation of Activated Oximes by ERs
Scheme 2
Scheme 2. Proposed Reaction Pathway from 1a to Pyrazine 2a through ER-Catalyzed Oxime Reduction and Spontaneous Oxidation
Scheme 3
Scheme 3. Cascade Reaction to Give d-Threonine Ethyl Ester 4 for the Indirect Proof of Intermediate 3
Scheme 4
Scheme 4. Chemoenzymatic Synthesis of Liguzinediol (6)
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