摘要：XuzhongShen1,XiaheChen2,YihangXiao1, Jesse B. Brown3, JamesG. Zhang1,XinyuanJi1,JinyanRui1, Marc Garcia-Borràs4,5,Yi Rao3*,Yunfang

转自：康龙化成

Enantioconvergent Benzylic C(sp3)‒N Coupling with a Copper-substituted Nonheme Enzyme

Xuzhong Shen1, Xiahe Chen2, Yihang Xiao1, Jesse B. Brown3, James G. Zhang1, Xinyuan Ji1, Jinyan Rui1, Marc Garcia-Borràs4,5, Yi Rao3*, Yunfang Yang2*, Xiongyi Huang1*

1 Department of Chemistry, Johns Hopkins University, Baltimore, MD, USA.

2 College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang, China.

3 Department of Chemistry and Biochemistry, Utah State University, Logan, UT, USA.

4 Institut de QuímicaComputacionaliCatàlisi(IQCC), Universitat de Girona, Catalonia, Spain.

5 Departament de Química, Universitat de Girona, Catalonia, Spain.

—Science, 2025, DOI: 10.1126/science.adt5986

Recommended by Yuquan Liu_PT

KEY WORDS:Biocatalysis,C-N coupling,Cucatalysis,photo chemistry, asymmetric synthesis (反应类型), c(sp3)-N (成键类型), NHPI ester (原料), amines (产物)

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 aphotoredox catalyst, we identified a copper-substituted phenylalanine hydroxylase that facilitates enantioconvergent decarboxylative amination between N-hydroxyphthalimideesters and anilines. Directed evolution remodeled the active site, resulting in high enantioselectivities for most substrates. On the basis ofmolecular modeling and mechanistic studies, they proposed 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.

Substrate scope (selected examples)

Plausible reaction mechanism and fluorescence quenching of rhodamine B (5.0 μM final concentration) by AH− (ascorbate) in the presence of CvPAH-aminase (1.0 μMfinal concentration)

Prof. Xiongyi Huang and Yunfang Yanget al have developed s a biocatalytic strategy for decarboxylative C‒N bond formation. This work also establishes PAHs as a powerful platform for enantioselective radical C‒N bond formation. They envisioned that interfacing various radical generation mechanisms with this metalloenzymatic platform will enable diverse biocatalytic amination reactions unprecedented in biology.

来源：新浪财经