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Published on: February 16, 2018
Directed Evolution of Nonheme Iron Enzymes for Enantioselective Aminative Difunctionalization of Alkenes
Fei Liu1,2, Si-Yi Li1,2, Zi-Shan Fan1,2
1Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Department of Biopharmaceutics, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Abstract:
The direct aminative difunctionalization of alkenes offers a powerful strategy for synthesizing valuable amine-containing compounds. However, achieving this transformation enantioselectively remains a significant challenge in both synthetic chemistry and biocatalysis. In this study, we engineered a nonheme iron enzyme, quercetin 2,3-dioxygenase from Bacillus subtilis (BsQueD), to catalyze three distinct alkene aminofunctionalization reactions with high efficiency and enantiocontrol. Through directed evolution, we developed an optimized BsQueD variant capable of producing a wide array of chiral 2-azidoamines, 2-aminothiazolines, and 2-aminooxazolines with up to 72% yield and 99:1 enantiomeric ratio (e.r.). Mechanistic investigations suggest a stepwise radical addition pathway. This work broadens the scope of biocatalytic alkene difunctionalization, providing a sustainable and efficient route for synthesizing diverse chiral primary amines.
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