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

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

doi:10.1021/acscatal.0c03755

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.

Highlights

The repertoire of chemical reactions gets constantly expanded,[1] including the spectrum of biocatalytic transformations by, for example, (i) exploiting light[2] or (ii) evolving enzymes for new reactions.[3]
Other reports indicated that whole-cell organisms such as Baker’s yeast or anaerobic organisms may enable the reduction of oximes to afford the corresponding hydroxylamines and/or amines or even pyrazines,[11] but the involved enzymes have never been identified
We report the reduction of an oxime to an amine by a specific enzyme, namely, ERs

Summary

■ INTRODUCTION

The repertoire of chemical reactions gets constantly expanded,[1] including the spectrum of biocatalytic transformations by, for example, (i) exploiting light[2] or (ii) evolving enzymes for new reactions.[3]. The oxime functionality can be chemically transformed via various established reactions[4] such as rearrangements[5] or chemical reductions, the latter leading to amines,[6] imines,[7] aziridines,[8] or hydroxylamines.[9] Biocatalytic transformations of oximes have been reported to give carbonyl compounds or alcohols only using baker’s yeast, alcohol dehydrogenases, or ene-reductases (ERs).[10] In these cases, the oxime was most likely transformed enzymatically to the corresponding imine, which was subsequently hydrolyzed spontaneously to the carbonyl compound. Other reports indicated that whole-cell organisms such as Baker’s yeast or anaerobic organisms may enable the reduction of oximes to afford the corresponding hydroxylamines and/or amines or even pyrazines,[11] but the involved enzymes have never been identified. We report the first enzymatic reduction of an oxime to an amine using ERs

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES