Organic and Inorganic Chemistry Department, University of Oviedo, Avenida Julián Clavería 8, 33006, Oviedo, Spain.
Current address: Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060, Wien, Austria.
Angew Chem Int Ed Engl. 2024 Sep 23;63(39):e202410283. doi: 10.1002/anie.202410283. Epub 2024 Aug 20.
The direct synthesis of alkenes from alkynes usually requires the use of transition-metal catalysts. Unfortunately, efficient biocatalytic alternatives for this transformation have yet to be discovered. Herein, the selective bioreduction of electron-deficient alkynes to alkenes catalysed by ene-reductases (EREDs) is described. Alkynes bearing ketone, aldehyde, ester, and nitrile moieties have been effectively reduced with excellent conversions and stereoselectivities, observing clear trends for the E/Z ratios depending on the nature of the electron-withdrawing group. In the case of cyanoalkynes, (Z)-alkenes were obtained as the major product, and the reaction scope was expanded to a wide variety of aromatic substrates (up to >99 % conversion, and Z/E stereoselectivities of up to >99/1). Other alkynes containing aldehyde, ketone, or ester functionalities also proved to be excellent substrates, and interestingly gave the corresponding (E)-alkenes. Preparative biotransformations were performed on a 0.4 mmol scale, producing the desired (Z)-cyanoalkenes with good to excellent isolated yields (63-97 %). This novel reactivity has been rationalised through molecular docking by predicting the binding poses of key molecules in the ERED-pu-0006 active site.
炔烃直接合成为烯烃通常需要使用过渡金属催化剂。然而，这种转化的高效生物催化替代方法尚未被发现。本文描述了烯还原酶（ERED）催化的缺电子炔烃的选择性生物还原为烯烃。带有酮、醛、酯和腈部分的炔烃已被有效地还原，转化率和立体选择性都很高，观察到 E/Z 比取决于吸电子基团的性质的明显趋势。在氰基炔烃的情况下，主要得到（Z）-烯烃，并且反应范围扩展到各种芳香族底物（高达>99%的转化率和高达>99/1 的 Z/E 立体选择性）。其他含有醛、酮或酯官能团的炔烃也被证明是很好的底物，并且有趣的是得到了相应的（E）-烯烃。在 0.4 mmol 规模上进行了制备性生物转化，以良好至优异的分离收率（63-97%）得到所需的（Z）-氰基烯烃。通过预测 ERED-pu-0006 活性位点中关键分子的结合构象，通过分子对接对这种新的反应性进行了合理化。
