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Published on: August 12, 2019
Enantioselective Trifluoromethylazidation of Styrenyl Olefins Catalyzed by an Engineered Nonheme Iron Enzyme
Hua He1,2, Jia-Xin Yan1,2, Jian-Xiang Zhu1,2
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:
Organofluorines, particularly those containing trifluoromethyl (CF3) groups, play a critical role in medicinal chemistry. While trifluoromethylation of alkenes provides a powerful synthetic route to construct CF3-containing compounds with broad structural and functional diversity, achieving enantioselective control in these reactions remains a formidable challenge. In this study, we engineered a nonheme iron enzyme, quercetin 2,3-dioxygenase from Bacillus subtilis (BsQueD), for the enantioselective trifluoromethylazidation of alkenes. Through directed evolution, the final variant BsQueD-CF3 exhibited excellent enantioselectivity, with an enantiomeric ratio (e.r.) of up to 98 : 2. Preliminary mechanistic studies suggest the involvement of radical intermediates. This work expands biocatalytic organofluorine chemistry by reprogramming metalloenzymes for innovative trifluoromethylation reactions.
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