羟基化
催化作用
氧化磷酸化
化学
衍生化
单加氧酶
手性(物理)
氧化加成
键裂
催化循环
立体化学
组合化学
有机化学
细胞色素P450
酶
生物化学
量子力学
物理
手征对称破缺
高效液相色谱法
Nambu–Jona Lasinio模型
夸克
作者
Qun Huang,Xuan Zhang,Qianqian Chen,Shaixiao Tian,Jian‐bo Wang,Wei Zhang,Yingzhuang Chen,Ming Ma,Bo Chen,Binju Wang,Jian‐bo Wang
标识
DOI:10.1021/acscatal.1c05510
摘要
While the enzymatic oxidative cleavage of C–F bonds at achiral centers catalyzed by P450 monooxygenases has been studied extensively, less is known about the oxidative defluorination mechanism of chiral substrates with fluorine being at chirality centers. Here, we report that the use of ethyl 2-fluoro-2-phenylacetate as a stereochemical probe enabled us to discover two oxidative defluorination paths catalyzed by P450-BM3: α-site hydroxylation and hydroxylation at the remote phenyl group. By means of intermediate identification and capture, chemical mimics, key intermediate derivatization, and deuterium insertion experiments as well as QM theoretical calculations, we succeeded in demonstrating an unusual mechanism in which these two oxidative defluorination routes occur in a P450 monooxygenase. This work presents valuable insights into the oxidative degradation of organofluorines and provides a convenient method for remote C–F bond activation.
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