立体中心
胺化
化学
生物催化
硝基苯
选择性
组合化学
立体化学
对映体
对映选择合成
手性(物理)
有机化学
催化作用
反应机理
Nambu–Jona Lasinio模型
手征对称破缺
物理
量子力学
夸克
作者
Runze Mao,Shilong Gao,Zi-Yang Qin,Torben Rogge,Sophia P. Wu,Zi‐Qi Li,Anuvab Das,K. N. Houk,Frances H. Arnold
标识
DOI:10.26434/chemrxiv-2023-8d2tc
摘要
Intermolecular functionalization of tertiary C–H bonds to construct fully substituted stereogenic carbon centers represents a formidable challenge: without the assistance of directing groups, the state-of-the-art catalysts struggle to introduce chirality to racemic tertiary sp3-carbon centers. Direct asymmetric functionalization of such centers is a worthy reactivity and selectivity goal for modern biocatalysis. Here we present an engineered nitrene transferase (P411-TEA-5274), derived from a bacterial cytochrome P450, that is capable of aminating tertiary C–H bonds to provide chiral α-tertiary primary amines with high efficiency (up to 2300 total turnovers) and selectivity (up to >99% enantiomeric excess (e.e.)). The construction of fully substituted stereocenters with methyl and ethyl groups underscores the enzyme’s remarkable selectivity. A comprehensive substrate scope study demonstrates the biocatalyst’s compatibility with diverse functional groups and tertiary C–H bonds. Mechanistic studies, incorporating both experimental and computational data, elucidate how active-site residues distinguish between the enantiomers and enable the enzyme to perform this transformation with excellent enantioselectivity.
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