The ability to selectively functionalize ubiquitous C-H bonds streamlines the construction of complex molecular architectures from easily available precursors. Here we report enzyme catalysts derived from a cytochrome P450 that use a nitrene transfer mechanism for the enantioselective amination of primary, secondary and tertiary C(sp3)-H bonds. These fully genetically encoded enzymes are produced and function in bacteria, where they can be optimized by directed evolution for a broad spectrum of enantioselective C(sp3)-H amination reactions. These catalysts can aminate a variety of benzylic, allylic and aliphatic C-H bonds in excellent enantioselectivity with access to either antipode of product. Enantioselective amination of primary C(sp3)-H bonds in substrates that bear geminal dimethyl substituents furnished chiral amines that feature a quaternary stereocentre. Moreover, these enzymes enabled the enantioconvergent transformation of racemic substrates that possess a tertiary C(sp3)-H bond to afford products that bear a tetrasubstituted stereocentre, a process that has eluded small-molecule catalysts. Further engineering allowed for the enantioselective construction of methyl-ethyl stereocentres, which is notoriously challenging in asymmetric catalysis.

中文翻译：

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用于伯、仲和叔 C(sp3)-H 键不对称胺化的酶平台。

选择性功能化普遍存在的 CH 键的能力简化了从容易获得的前体构建复杂分子结构的过程。在此，我们报道了源自细胞色素 P450 的酶催化剂，该催化剂使用氮宾转移机制对伯、仲和叔 C(sp3)-H 键进行对映选择性胺化。这些完全基因编码的酶在细菌中产生并发挥作用，可以通过定向进化来优化它们，以实现广泛的对映选择性 C(sp3)-H 胺化反应。这些催化剂可以以优异的对映选择性胺化各种苄基、烯丙基和脂肪族 CH 键，并获得产物的任一对映体。带有偕二甲基取代基的底物中伯 C(sp3)-H 键的对映选择性胺化提供了具有四元立构中心的手性胺。此外，这些酶能够实现具有叔C(sp3)-H键的外消旋底物的对映体转化，以提供带有四取代立构中心的产物，这是小分子催化剂无法实现的过程。进一步的工程允许对映选择性构建甲基乙基立构中心，这在不对称催化中是众所周知的挑战。