AbstractHere, we report a general approach to the synthesis of the difluoroalkyl bicycloalkanes (CF2‐BCAs), as structural surrogates of aryl ketones and ethers. The chemistry is driven by a dihydrobenzoacridine photocatalyst, that engages in a catalytic electron‐donor acceptor (EDA) complex, or directly reduces the fluorinated substrate. These two convergent manifolds lead to the generation of the R‐CF2 radical, that reacts with the [1.1.1]‐ or [3.1.1.]‐propellane. The method is extremely general, and extendable to complex bioactive molecules (30 examples, up to 87 % yield). The structural features of the CF2‐BCP hybrid bioisostere were investigated by single crystal X‐ray. Finally, we synthesised a CF2‐BCP analogue of a Leukotriene A4 hydrolase inhibitor, replacing the original aryl ether motif. In silico docking studies indicated that this new analogue maintains the same arrangement within the enzyme pocket, profiling the use of the CF2‐BCA hybrid bioisostere in medicinal chemistry settings.

中文翻译：

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二氟烷基双环烷烃 (CF2-BCA) 混合生物等排体的通用有机光氧化还原策略**

摘要在这里，我们报告了合成二氟烷基双环烷烃（CF2‐BCAs），作为芳基酮和醚的结构替代物。该化学反应由二氢苯并吖啶光催化剂驱动，该催化剂参与催化电子供体受体（EDA）复合物，或直接还原氟化底物。这两个收敛流形导致 R-CF 的生成2自由基，与[1.1.1]-或[3.1.1.]-丙烷反应。该方法极其通用，可扩展到复杂的生物活性分子（30 个示例，产率高达 87%）。CF的结构特点2‐通过单晶 X 射线研究 BCP 杂化生物等排体。最后我们合成了一个CF2‐白三烯 A 的 BCP 类似物4水解酶抑制剂，取代原来的芳基醚基序。计算机对接研究表明，这种新的类似物在酶袋内保持相同的排列，分析了 CF 的使用2‐药物化学环境中的 BCA 混合生物电子等排体。