Abstract
α,β-Unsaturated esters are versatile building blocks for organic synthesis and of significant importance for industrial applications. A great variety of synthetic methods have been developed, and quite a number of them use aldehydes as precursors. Herein we report a chemo-enzymatic chain elongation approach to access α,β-unsaturated esters by combining an enzymatic carboxylic acid reduction and Wittig reaction. Recently, we have found that Mycobacterium sp. was able to reduce phenylacetic acid (1a) to 2-phenyl-1-ethanol (1c) and two sequences in the Mycobacterium sp. genome had high identity with the carboxylic acid reductase (CAR) gene from Nocardia iowensis. These two putative CAR genes were cloned, overexpressed in E. coli and one of two proteins could reduce 1a. The recombinant CAR was purified and characterized. The enzyme exhibited high activity toward a variety of aromatic and aliphatic carboxylic acids, including ibuprofen. The Mycobacterium CAR catalyzed carboxylic acid reduction to give aldehydes, followed by a Wittig reaction to afford the products α,β-unsaturated esters with extension of two carbon atoms, demonstrating a new chemo-enzymatic method for the synthesis of these important compounds.
Highlights
Abundant component of biomass, the effective methods for the degradation of lignin need to be developed. These carboxylic acids could be reduced to their corresponding aldehydes, which can be used as starting materials for Wittig reaction
We report a new carboxylic acid reductase (CAR) from Mycobacterium sp. (Mycobacterium CAR) and its application in a chemo-enzymatic chain elongation method for the preparation of α,β-unsaturated esters by combining an enzymatic carboxylic acid reduction and Wittig reaction
Nineteen actinomycete strains available in our laboratory were screened for the carboxylic acid reductase activity using phenylacetic acid (1a) as the substrate by gas chromatography (GC) analysis of the products
Summary
Address: National Engineering Laboratory for Industrial Enzymes and Tianjin Engineering Center for Biocatalytic Technology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, P. R. China Keywords: α,β-unsaturated esters; carboxylic acid reductase; chemoenzymatic synthesis; reduction; Wittig reaction
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