通过[1.1.1]丙烷的多组分双官能化反应，实现 BCP 烷基伯胺的通用和模块化方法。
A General and Modular Approach to BCP Alkylamines via Multicomponent Difunctionalization of [1.1.1]Propellane.
机构信息
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
Medicinal Chemistry Department, Neuroscience Discovery Research, AbbVie Deutschland GmbH & Co. KG, 67061 Ludwigshafen, Germany.
出版信息
J Am Chem Soc. 2023 Mar 8;145(9):5363-5369. doi: 10.1021/jacs.2c13298. Epub 2023 Feb 21.
Over the past decade, bicyclo[1.1.1]pentane (BCP) motifs have come to the fore as valuable pharmaceutical bioisosteres of -disubstituted benzenes. However, the limited approaches and requisite multistep syntheses of useful BCP building blocks are hampering early discovery research in medicinal chemistry. Herein we report the development of a modular strategy for the divergent preparation of functionalized BCP alkylamines. In this process, a general method to introduce fluoroalkyl groups to BCP scaffolds using readily available and easy-to-handle fluoroalkyl sulfinate salts was also developed. Moreover, this strategy can also be extended to S-centered radicals for incorporation of sulfones and thioethers into the BCP core. Overall, this multicomponent strategy enables rapid construction of BCP-type bioisosteres for applications in drug discovery.
在过去的十年中，双环[1.1.1]戊烷（BCP）结构作为 - 二取代苯的有价值的药物生物等排体已经崭露头角。然而，有用的 BCP 构建块的有限方法和必要的多步合成阻碍了药物化学的早期发现研究。在此，我们报告了一种用于制备功能化 BCP 烷基胺的发散性模块化策略的开发。在这个过程中，还开发了一种使用易得且易于处理的氟烷基亚磺酸盐将氟烷基基团引入 BCP 支架的通用方法。此外，该策略还可以扩展到 S 中心自由基，以将砜和硫醚引入 BCP 核中。总的来说，这种多组分策略能够快速构建 BCP 型生物等排体，用于药物发现。
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