Key Laboratory of Cluster Science of Ministry of Education, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, 100081, Beijing, P. R. China.
Chem Asian J. 2022 Sep 1;17(17):e202200438. doi: 10.1002/asia.202200438. Epub 2022 Jul 13.
Selective halogenation is important in synthetic chemistry. BesD, a new member of the non-heme Fe(II)/α-ketoglutarate (αKG)-dependent halogenase family, can activate the sp C-H bond and halogenate lysine, in particular without a carrier protein. Using the density functional calculations, a chlorination mechanism in BesD has been proposed, mainly including the formation of Cl-Fe(IV)=O through the αKG decarboxylation, the isomerization of Cl-Fe(IV)=O, the substrate hydrogen abstraction by Fe(IV)=O, and the rebound of chloro to the substrate carbon radical. The hydrogen abstraction is rate-limiting. The isomerization of Cl-Fe(IV)=O is essential for the hydrogen abstraction and the chiral selectivity. The BesD-catalyzed bromination and azidation of lysine adopt the same mechanism as the chlorination. The hardly-changed overall barriers indicate that the introduced ligands (X) do not affect the reaction rate significantly, implying that the X-introduced reactions catalyzed by BesD may be extended to other X anions.
选择性卤化在合成化学中很重要。BesD 是新型非血红素 Fe(II)/α-酮戊二酸（αKG）依赖性卤化酶家族的成员，能够激活 sp³C-H 键并卤化赖氨酸，特别是在没有载体蛋白的情况下。通过密度泛函计算，提出了 BesD 中的氯化机制，主要包括通过 αKG 脱羧形成 Cl-Fe(IV)=O、Cl-Fe(IV)=O 的异构化、Fe(IV)=O 对底物的氢提取以及氯原子返回到底物碳自由基。氢提取是限速步骤。Cl-Fe(IV)=O 的异构化对于氢提取和手性选择性很重要。BesD 催化的赖氨酸的溴化和氮化采用与氯化相同的机制。变化不大的总势垒表明，引入的配体（X）不会显著影响反应速率，这意味着 BesD 催化的引入 X 的反应可能会扩展到其他 X 阴离子。
