Biosynthesis of α-Substituted β-Ketoesters via the Tandem Knoevenagel Condensation–Reduction Reaction Using a Single Enzyme,ACS Sustainable Chemistry & Engineering

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Biosynthesis of α-Substituted β-Ketoesters via the Tandem Knoevenagel Condensation–Reduction Reaction Using a Single Enzyme
ACS Sustainable Chemistry & Engineering ( IF 7.1 ) Pub Date : 2020-05-15 , DOI: 10.1021/acssuschemeng.0c00938
Xiaolong Liu ₁ , Xiangjie Li ₁ , Zhelun Wang ₁ , Jinlong Zhou ₁ , Xinjiong Fan _{1,

2} , Yao Fu _{1,

3}

Affiliation

Saturated α-substituted β-ketoesters are important building blocks in the synthesis of pharmaceuticals and agrochemicals. Herein, we report a one-pot biosynthesis of α-substituted β-ketoesters via Knoevenagel condensation and reduction of the obtained unsaturated alkenes in situ, catalyzed by a single ene-reductase (NerA). A series of inexpensive and readily available aldehydes and 1,3-diketones were condensed and reduced by NerA in aqueous solutions at room temperature. We also noted that low loadings (3 mg/mL) of NerA were sufficient to facilitate the cascade process; both E and Z isomeric intermediates could be reduced effectively, and the overall yield was improved up to 95%. Meanwhile, the method could be applied to a gram preparative-scale synthesis of pharmaceutical intermediates. This process conformed to the concepts of green chemistry and showed advantages for the synthesis of high value saturated α-substituted β-ketoesters.

中文翻译：

通过单酶串联Knoevenagel缩合-还原反应生物合成α-取代的β-酮酸酯

饱和的α-取代的β-酮酸酯是药物和农用化学品合成中的重要组成部分。在这里，我们报道了通过单烯键还原酶（NerA）催化的Knoevenagel缩合和原位还原获得的不饱和烯烃一锅法合成α-取代的β-酮酸酯。在室温下，NerA在水溶液中将一系列廉价且易于获得的醛和1,3-二酮缩合并还原。我们还注意到，NerA的低负载量（3 mg / mL）足以促进级联过程。既Ë和ž异构中间体可以有效减少，总收率提高到95％。同时，该方法可应用于克制备规模的医药中间体的合成。该方法符合绿色化学的概念，并显示出合成高价值的饱和α-取代的β-酮酸酯的优势。

更新日期：2020-05-15

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