Biosynthesis of α-Substituted β-Ketoesters via the Tandem Knoevenagel Condensation–Reduction Reaction Using a Single EnzymeClick to copy article linkArticle link copied!
- Xiaolong LiuXiaolong LiuSchool of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, ChinaMore by Xiaolong Liu
- Xiangjie LiXiangjie LiSchool of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, ChinaMore by Xiangjie Li
- Zhelun WangZhelun WangSchool of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, ChinaMore by Zhelun Wang
- Jinlong ZhouJinlong ZhouSchool of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, ChinaMore by Jinlong Zhou
- Xinjiong Fan*Xinjiong Fan*Email: [email protected]School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, ChinaSchool of Basic Medical Sciences, Anhui Medical University, 81 Meishan Rd., Hefei, Anhui 230032, People’s Republic of ChinaMore by Xinjiong Fan
- Yao Fu*Yao Fu*Email: [email protected]School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, ChinaHefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Urban Pollutant Conversion, Anhui Province Key Laboratory of Biomass Clean Energy, iChEM, University of Science and Technology of China, Hefei, Anhui 230026, ChinaMore by Yao Fu
Abstract
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.
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