西湖大学叶宇轩团队揭示了烯还原酶对不对称羰基脱饱和的反催化活性。相关研究成果发表在2024年11月26日出版的《自然—化学》。

羰基脱饱和是有机合成中广泛应用的一种基本反应。虽然已经开发了许多方法来扩大这一重要转变的范围，但其中大多数方法都需要多步骤协议，或者使用高负载金属或强氧化条件。此外，能够实现去饱和过程精确立体化学控制的方法极为罕见。

该文中，研究人员报告了一种生物催化平台，通过重组“烯”还原酶有效地介导脱氢，即其天然活性的反向过程，使环己酮不对称脱饱和，从而产生具有远程季立体中心的各种环己烯酮。

这种基于“烯”还原酶的去饱和系统在温和条件下运行，以空气作为末端氧化剂，耐受氧化敏感或金属不相容的官能团，更重要的是，与小分子催化剂相比，它表现出无与伦比的立体选择性。机理研究表明，反应是通过α-脱质子化进行的，然后是决定速率的β-氢化物转移。

附：英文原文

Title: Unmasking the reverse catalytic activity of ‘ene’-reductases for asymmetric carbonyl desaturation

Author: Wang, Hui, Gao, Bin, Cheng, Heli, Cao, Shixuan, Ma, Xinyi, Chen, Yinjuan, Ye, Yuxuan

Issue&Volume: 2024-11-26

Abstract: Carbonyl desaturation is a fundamental reaction widely practised in organic synthesis. While numerous methods have been developed to expand the scope of this important transformation, most of them necessitate multi-step protocols or suffer from the use of high loadings of metal or strong oxidizing conditions. Moreover, approaches that can achieve precise stereochemical control of the desaturation process are extremely rare. Here we report a biocatalytic platform for desymmetrizing desaturation of cyclohexanones to generate diverse cyclohexenones bearing a remote quaternary stereogenic centre, by reengineering ‘ene’-reductases to efficiently mediate dehydrogenation, the reverse process of their native activity. This ‘ene’-reductase-based desaturation system operates under mild conditions with air as the terminal oxidant, tolerates oxidation-sensitive or metal-incompatible functional groups and, more importantly, exhibits unparalleled stereoselectivity compared with those achieved with small-molecule catalysts. Mechanistic investigations suggest that the reaction proceeded through α-deprotonation followed by a rate-determining β-hydride transfer.

DOI: 10.1038/s41557-024-01671-1

Source: https://www.nature.com/articles/s41557-024-01671-1