电化学C-O和C-N结合利用交替极性流动用于复合库的流动
Jennifer Morvan1, Koen P L Kuijpers2, Dayne Fanfair2
1Global Discovery Chemistry, Janssen Research and Development, Turnhoutseweg 30, 2340, Beerse, Belgium.
Angewandte Chemie (International ed. in English)
|October 9, 2024
概括
我们开发了一个自动流电化学平台,用于合成C-X (X=NH,OH) 化化合物库. 这种方法为药物化学提供了强大而可扩展的方法,使得能够快速探索结构-活性关系.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 电化学 电化学 电化学
背景情况:
- 化乙烯的化和氨化是药物化学中用于结构-活性关系 (SAR) 研究的关键反应.
- 电化学方法在功能组耐受性和核范围方面比传统的合成方法具有优势.
- 现有的电化学方法缺乏对图书馆合成的强大和可扩展的工作流.
研究的目的:
- 开发一个基于流量的自动化电化学平台,用于合成C-X (X=NH,OH) 化化合物库.
- 使用实验设计 (DoE) 优化反应条件,以获得广泛的基质范围和高产量.
- 建立一个可复制和可扩展的方法来生成多样化的化学库.
主要方法:
- 自动合成平台利用流电化学进行C-X arylation.
- 综合实验设计 (DoE) 用于协议优化.
- 潜在静态交替极性策略,以防止电极被动化.
- 利用商业上可用的设备来创建图书馆.
主要成果:
- 在30多种烯化物支架,多种氨基和酒精 (包括酸中的氨酸) 中获得了高产量.
- 通过自动化反应序列成功生成了anilines和aryl ethers的库.
- 在没有支持电解质的情况下,在空气中证明了反应可行性.
- 确保在连续运行的高可重复性.
结论:
- 开发的平台提供了一种强大而自动化的方法,用于合成核独立的C-X化化合物库.
- 流电化学为药物发现中的快速库存生成提供了可扩展和强大的解决方案.
- 使用潜在静态交替极性提高了电化学合成在流中的效率和适用性.
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