通过高度对映选择性[1,2]-史蒂文斯重排反应，生物催化的氮丙啶的一碳环扩环反应生成氮杂环丁烷。
Biocatalytic One-Carbon Ring Expansion of Aziridines to Azetidines via a Highly Enantioselective [1,2]-Stevens Rearrangement.
机构信息
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
出版信息
J Am Chem Soc. 2022 Mar 23;144(11):4739-4745. doi: 10.1021/jacs.2c00251. Epub 2022 Mar 8.
Abstract
We report enantioselective one-carbon ring expansion of aziridines to make azetidines as a new-to-nature activity of engineered "carbene transferase" enzymes. A laboratory-evolved variant of cytochrome P450, P411-AzetS, not only exerts unparalleled stereocontrol (99:1 er) over a [1,2]-Stevens rearrangement but also overrides the inherent reactivity of aziridinium ylides, cheletropic extrusion of olefins, to perform a [1,2]-Stevens rearrangement. By controlling the fate of the highly reactive aziridinium ylide intermediates, these evolvable biocatalysts promote a transformation which cannot currently be performed using other catalyst classes.
摘要
我们报告了氮丙啶的对映选择性一碳环扩张，以将氮杂环丁烷转化为氮杂环丁烷，这是工程化“碳烯转移酶”酶的一种新的天然活性。细胞色素 P450 的实验室进化变体 P411-AzetS，不仅对[1,2]-史蒂文斯重排具有无与伦比的立体控制（99:1er），而且还可以克服氮丙啶叶立德的固有反应性，即烯烃的cheletropic 挤出，以进行[1,2]-史蒂文斯重排。通过控制高反应性氮丙啶叶立德中间体的命运，这些可进化的生物催化剂促进了一种目前无法使用其他催化剂类别进行的转化。
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