Chemo-Enzymatic Synthesis of Pyrazines and Pyrroles.

Jin Xu,Nicholas J Turner,Anthony P Green

doi:10.1002/anie.201810555

Jin Xu, Nicholas J Turner + Show 1 more

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https://doi.org/10.1002/anie.201810555

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Abstract

Herein we report the biocatalytic synthesis of substituted pyrazines and pyrroles using a transaminase (ATA) to mediate the key amination step of the ketone precursors. Treatment of α‐diketones with ATA‐113 in the presence of a suitable amine donor yielded the corresponding α‐amino ketones which underwent oxidative dimerization to the pyrazines. Selective amination of α‐diketones in the presence of β‐keto esters afforded substituted pyrroles in a biocatalytic equivalent of the classical Knorr pyrrole synthesis. Finally we have shown that pyrroles can be prepared by internal amine transfer catalyzed by a transaminase in which no external amine donor is required.

Highlights

Abstract: we report the biocatalytic synthesis of substituted pyrazines and pyrroles using a transaminase (ATA) to mediate the key amination step of the ketone precursors
We have shown that pyrroles can be prepared by internal amine transfer catalyzed by a transaminase in which no external amine donor is required
We show that ATAs can be employed for the synthesis of N-heteroaromatic compounds, pyrazines and pyrroles, and demonstrate advantages of using biocatalysis over conventional methods for the preparation of these compounds

Summary

Introduction

Abstract: we report the biocatalytic synthesis of substituted pyrazines and pyrroles using a transaminase (ATA) to mediate the key amination step of the ketone precursors. Treatment of a-diketones with ATA-113 in the presence of a suitable amine donor yielded the corresponding a-amino ketones which underwent oxidative dimerization to the pyrazines. Selective amination of a-diketones in the presence of b-keto esters afforded substituted pyrroles in a biocatalytic equivalent of the classical Knorr pyrrole synthesis.

Results

Conclusion