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科学家实现光酶对映选择性分子间自由基氢烷基化
2020-06-11 16:08

美国伊利诺伊大学香槟分校Huimin Zhao团队实现了光酶对映选择性分子间自由基氢烷基化。该项研究成果于2020年6月8日在线发表在《自然》杂志上。

研究人员发现了一种新的、自然可见光诱导的烯还原酶催化的末端烯烃与α-卤代羰基化合物的分子间自由基加氢烷基化反应。该方法为具有γ-立体中心的各种羰基化合物提供了一种有效的方法,其具有优异的收率和对映选择性(高达99%的收率,99%的对映体过量),否则很难通过化学催化获得。
 
机理研究表明,在酶活性位点的底物/烯-还原酶复合物的形成触发了对映选择性光诱导的自由基反应。这项工作通过将光催化和酶催化相结合,进一步扩展了生物催化、合成上有价值的不对称转化反应活性。
 
据悉,越来越多不对称合成酶被发现,但它们的应用通常受到天然酶中已有反应的限制。最近,对光催化的兴趣促使人们从已知的酶中发现新的反应性。但是,到目前为止,光诱导的酶催化尚未用于两个分子的交叉偶联。例如,酶尚未能够实现烯烃与α-卤代羰基化合物的分子间偶联(通过可见光引起的自由基加氢烷基化)。目前主要的难点是酶固有的不良光反应性,以及远程前手性自由基中间体的立体化学控制。
 
附:英文原文

Title: Photoenzymatic enantioselective intermolecular radical hydroalkylation

Author: Xiaoqiang Huang, Binju Wang, Yajie Wang, Guangde Jiang, Jianqiang Feng, Huimin Zhao

Issue&Volume: 2020-06-08

Abstract: Enzymes are increasingly explored for asymmetric synthesis1–3, but their applications are generally limited by the reactions available to naturally occurring enzymes. Recently, interest in photocatalysis4 has spurred the discovery of new reactivity from known enzymes5. However, so far photo-induced enzymatic catalysis6 has not been used for cross-coupling of two molecules. For example, intermolecular coupling of alkenes with α-halo carbonyl compounds through a visible-light-induced radical hydroalkylation, which could provide access to important γ-chiral carbonyl compounds, has not yet been achieved by enzymes. The major challenges are the inherent poor photoreactivity of enzymes and the difficulty in stereochemical control of the remote prochiral radical intermediate7. Here we show a new-to-nature, visible-light-induced ene-reductase catalysed intermolecular radical hydroalkylation of terminal alkenes with readily available α-halo carbonyl compounds. This method provides an efficient approach to various carbonyl compounds bearing a γ-stereocentre with excellent yields and enantioselectivities (up to 99% yield, 99% enantiomeric excess), which otherwise are difficult to access by chemocatalysis. Mechanistic studies suggest that the substrates/ene-reductase complex formation at the enzyme active site triggers the enantioselective photo-induced radical reaction. Our work further expands the reactivity repertoire of biocatalytic, synthetically-useful asymmetric transformations by the merger of photocatalysis and enzyme catalysis.

DOI: 10.1038/s41586-020-2406-6

Source: https://www.nature.com/articles/s41586-020-2406-6

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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