实现电化学,脱碳化C2 -C3交叉合,用于并行药物化学
Jennifer Morvan1, Bingqing Tang1, Pavel Ryabchuk1
1Global Discovery Chemistry, Janssen Research and Development, Turnhoutseweg 30, Beerse, 2340 Belgium.
European journal of medicinal chemistry
|April 12, 2025
概括
我们开发了一种自动化,无净化电化学方法,可以将碳酸和化结合起来. 这促进了用于药物发现的C(sp2) -C(sp3) 键形成,使得快速的库合成成为可能.
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:
- 碳氧酸是药物化学中的多功能构建块.
- 对于C(sp2) -C(sp3) 键形成的脱碳氧化交叉合是具有挑战性的.
- 使用氧化还原活性 (RAE) 的现有方法可以产生对催化有害的副产品.
研究的目的:
- 开发一种自动化,无净化协议来激活碳酸酸.
- 为了实现高效的电化学脱碳化交叉合.
- 促进复合库的合成,包括PROTACs.
主要方法:
- 作为N-hydroxyphthalimide (NHPI) 埃斯特的炭酸的激活.
- 高通量,自动化电化学脱碳化交叉合.
- 没有净化的协议设计.
主要成果:
- 在温和的电化学条件下成功合亚利法性碳酸和烯化物.
- 在准备复合库和PROTAC中证明了适用性.
- 克服了以前基于RAE的方法的局限性.
结论:
- 开发的自动化协议简化了C ((sp2) -C ((sp3) 债券形成.
- 这种方法扩大了随时可用的碳酸在药物发现中的实用性.
- 该协议有可能影响未来制药研究中的交叉合策略.
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