Photoenzymatic enantioselective synthesis of fluorinated amides with remote stereocenter
Abstract Fluorinated compounds are scarce in nature, albeit they are in high demand in pharmaceuticals, agrochemicals, and materials. Fluorinated amides serve as prevalent structural motifs in pharmaceuticals and bioactive molecules. However, enantioselective synthesis of fluorinated amides remains...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60807-0 |
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| author | Chaoqun Huang Xuerui Jin Zhenyu Liu Can Cui Yang Zhang Binju Wang Chun Zhang Jianqiang Feng Dawen Niu Yunzi Luo |
| author_facet | Chaoqun Huang Xuerui Jin Zhenyu Liu Can Cui Yang Zhang Binju Wang Chun Zhang Jianqiang Feng Dawen Niu Yunzi Luo |
| author_sort | Chaoqun Huang |
| collection | DOAJ |
| description | Abstract Fluorinated compounds are scarce in nature, albeit they are in high demand in pharmaceuticals, agrochemicals, and materials. Fluorinated amides serve as prevalent structural motifs in pharmaceuticals and bioactive molecules. However, enantioselective synthesis of fluorinated amides remains challenging. Herein, we develop a visible-light-driven ene-reductase system that effectively generates carbon-centered radicals from fluorine-containing brominated amides. The system further enables their enantioselective hydroalkylation with alkenes, achieving high stereocontrol. Diversified α-fluorinated amides with high yield (up to 91%) and distal chirality (γ-to F, up to 97% enantiomeric excess) are produced by optimizing the reaction system and performing enzyme engineering. This work advances photoenzymatic strategies for the integration of fluorinated chemical inputs and creates an opportunity for the asymmetric synthesis of valuable fluorinated compounds. |
| format | Article |
| id | doaj-art-a3a3f5930b6941b9a8b17a69f115d8d7 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a3a3f5930b6941b9a8b17a69f115d8d72025-08-20T04:01:36ZengNature PortfolioNature Communications2041-17232025-07-0116111110.1038/s41467-025-60807-0Photoenzymatic enantioselective synthesis of fluorinated amides with remote stereocenterChaoqun Huang0Xuerui Jin1Zhenyu Liu2Can Cui3Yang Zhang4Binju Wang5Chun Zhang6Jianqiang Feng7Dawen Niu8Yunzi Luo9Frontiers Science Center for Synthetic Biology (Ministry of Education), School of Synthetic Biology and Biomanufacturing, Tianjin UniversityFrontiers Science Center for Synthetic Biology (Ministry of Education), School of Synthetic Biology and Biomanufacturing, Tianjin UniversityFrontiers Science Center for Synthetic Biology (Ministry of Education), School of Synthetic Biology and Biomanufacturing, Tianjin UniversityFrontiers Science Center for Synthetic Biology (Ministry of Education), School of Synthetic Biology and Biomanufacturing, Tianjin UniversityDepartment of Emergency, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital and School of Chemical Engineering, Sichuan UniversityState Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen UniversityState Key Laboratory of Synthetic Biology, Tianjin UniversityInstitute of Molecular Engineering Plus, College of Chemistry, Fuzhou UniversityDepartment of Emergency, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital and School of Chemical Engineering, Sichuan UniversityFrontiers Science Center for Synthetic Biology (Ministry of Education), School of Synthetic Biology and Biomanufacturing, Tianjin UniversityAbstract Fluorinated compounds are scarce in nature, albeit they are in high demand in pharmaceuticals, agrochemicals, and materials. Fluorinated amides serve as prevalent structural motifs in pharmaceuticals and bioactive molecules. However, enantioselective synthesis of fluorinated amides remains challenging. Herein, we develop a visible-light-driven ene-reductase system that effectively generates carbon-centered radicals from fluorine-containing brominated amides. The system further enables their enantioselective hydroalkylation with alkenes, achieving high stereocontrol. Diversified α-fluorinated amides with high yield (up to 91%) and distal chirality (γ-to F, up to 97% enantiomeric excess) are produced by optimizing the reaction system and performing enzyme engineering. This work advances photoenzymatic strategies for the integration of fluorinated chemical inputs and creates an opportunity for the asymmetric synthesis of valuable fluorinated compounds.https://doi.org/10.1038/s41467-025-60807-0 |
| spellingShingle | Chaoqun Huang Xuerui Jin Zhenyu Liu Can Cui Yang Zhang Binju Wang Chun Zhang Jianqiang Feng Dawen Niu Yunzi Luo Photoenzymatic enantioselective synthesis of fluorinated amides with remote stereocenter Nature Communications |
| title | Photoenzymatic enantioselective synthesis of fluorinated amides with remote stereocenter |
| title_full | Photoenzymatic enantioselective synthesis of fluorinated amides with remote stereocenter |
| title_fullStr | Photoenzymatic enantioselective synthesis of fluorinated amides with remote stereocenter |
| title_full_unstemmed | Photoenzymatic enantioselective synthesis of fluorinated amides with remote stereocenter |
| title_short | Photoenzymatic enantioselective synthesis of fluorinated amides with remote stereocenter |
| title_sort | photoenzymatic enantioselective synthesis of fluorinated amides with remote stereocenter |
| url | https://doi.org/10.1038/s41467-025-60807-0 |
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