Expanding the Promiscuity of a Copper‐Dependent Oxidase for Enantioselective Cross‐Coupling of Indoles

Author:

Guo Huan1,Sun Ningning1,Guo Juan1,Zhou Tai‐Ping1,Tang Langyu1,Zhang Wentao1,Deng Yaming1,Liao Rong‐Zhen1,Wu Yuzhou1,Wu Guojiao1,Zhong Fangrui1ORCID

Affiliation:

1. Hubei Engineering Research Center for Biomaterials and Medical Protective Materials Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica School of Chemistry and Chemical Engineering Huazhong University of Science and Technology (HUST) Luoyu Road 1037 Wuhan 430074 China

Abstract

AbstractHerein, we disclose the highly enantioselective oxidative cross‐coupling of 3‐hydroxyindole esters with various nucleophilic partners as catalyzed by copper efflux oxidase. The biocatalytic transformation delivers functionalized 2,2‐disubstituted indolin‐3‐ones with excellent optical purity (90–99 % ee), which exhibited anticancer activity against MCF‐7 cell lines, as shown by preliminary biological evaluation. Mechanistic studies and molecular docking results suggest the formation of a phenoxyl radical and enantiocontrol facilitated by a suited enzyme chiral pocket. This study is significant with regard to expanding the catalytic repertoire of natural multicopper oxidases as well as enlarging the synthetic toolbox for sustainable asymmetric oxidative coupling.

Funder

National Key Research and Development Program of China

Publisher

Wiley

Subject

General Medicine

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