近日，浙江工业大学杨云芳团队研究了对映收敛苯基C(sp3)N与铜取代的非血红素酶偶联。相关论文于2025年8月14日发表在《科学》杂志上。

近十年来，铜催化自由基C(sp³)N偶联已成为合成催化领域的研究热点。然而，通过酶的主题化来实现这种反应的多样性仍然是很困难的。

研究组介绍了一种光生物催化自由基苯基C(sp³)N偶联修饰铜取代非血红素酶。使用罗丹明B作为光氧化还原催化剂，研究组确定了铜取代的苯丙氨酸羟化酶，促进N-羟基邻苯二胺酯和苯胺之间的对映收敛脱羧胺化。定向进化重塑了活性位点，导致对大多数底物具有高对映选择性。在分子模型和机理研究的基础上，研究组提出该酶可容纳与苯胺自由基反应的铜-苯胺配合物。该研究将非天然生物催化过渡金属催化的范围扩展到铜催化的自由基偶联。

附：英文原文

Title: Enantioconvergent benzylic C(sp3)N coupling with a copper-substituted nonheme enzyme

Author: Xuzhong Shen, Xiahe Chen, Yihang Xiao, Jesse B. Brown, James G. Zhang, Xinyuan Ji, Jinyan Rui, Marc Garcia-Borràs, Yi Rao, Yunfang Yang, Xiongyi Huang

Issue&Volume: 2025-08-14

Abstract: Copper-catalyzed radical C(sp3)N coupling has become a major focus in synthetic catalysis over the past decade. However, achieving this reaction manifold by using enzymes has remained elusive. In this study, we introduce a photobiocatalytic approach for radical benzylic C(sp3)N coupling using a copper-substituted nonheme enzyme. Using rhodamine B as a photoredox catalyst, we identified a copper-substituted phenylalanine hydroxylase that facilitates enantioconvergent decarboxylative amination between N-hydroxyphthalimide esters and anilines. Directed evolution remodeled the active site, resulting in high enantioselectivities for most substrates. On the basis of molecular modeling and mechanistic studies, we propose that the enzyme accommodates a copper-anilide complex that reacts with a benzylic radical. This study expands the scope of non-natural biocatalytic transition metal catalysis to copper-catalyzed radical coupling.

DOI: adt5986

Source: https://www.science.org/doi/10.1126/science.adt5986