In the past decade, biocatalysis has come to the forefront of synthetic chemistry, demonstrating mild, green, and highly enantio- and chemoselective syntheses of chiral compounds. To date, however, there is no general method for the enzymatic reduction of α,β-unsaturated carboxylic acids to synthesize α-substituted chiral acids. Due to the acid moeity being poorly electron negative, they are not active enough to undergo reduction by enonate reductases (ERED). Herein this presentation, we identify a highly promiscuous ERED that reduces α,β-unsaturated acids to generate chiral α-substituted acids in up to &gt;99% ee. ERED 36 accepted a wide range of aromatic and aliphatic acrylic acids as well as unsaturated cyclic carboxylic acids. Protein modelling studies provided mechanistic insight into the enzyme’s ability to reduce unsaturated acids. A deeper understanding of this enzyme will enable future design of enzyme’s to reduce even more challenging and deactivated substrates enantioselectively.

Enantioselective synthesis of α-propanoic acids via enzymatic reduction of acrylic acids

ACS Fall 2020 Virtual Meeting

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