Huang Chaoqun, Jin Xuerui, Liu Zhenyu, Cui Can, Zhang Yang, Wang Binju, Zhang Chun, Feng Jianqiang, Niu Dawen, Luo Yunzi
Frontiers Science Center for Synthetic Biology (Ministry of Education), School of Synthetic Biology and Biomanufacturing, Tianjin University, Tianjin, China.
State Key Laboratory of Synthetic Biology, Tianjin University, Tianjin, China.
Nat Commun. 2025 Jul 1;16(1):5753. doi: 10.1038/s41467-025-60807-0.
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.
含氟化合物在自然界中稀缺，尽管它们在制药、农用化学品和材料领域有很高的需求。含氟酰胺是药物和生物活性分子中普遍存在的结构基序。然而，含氟酰胺的对映选择性合成仍然具有挑战性。在此，我们开发了一种可见光驱动的烯还原酶系统，该系统能有效地从含氟溴代酰胺中产生碳中心自由基。该系统还能使它们与烯烃进行对映选择性氢烷基化反应，实现高度的立体控制。通过优化反应体系和进行酶工程改造，可高产率（高达91%）和高远端手性（相对于氟的γ位，对映体过量高达97%）地制备多种α-氟代酰胺。这项工作推动了用于整合含氟化学原料的光酶策略，并为有价值的含氟化合物的不对称合成创造了机会。
