催化不对称的双重赫克/索诺加希拉反应,使人们能够访问多功能合式桥梁环架
Jing Zhong1, Mengxian Li1, Changhui Wu2
1State Key Laboratory of Natural Medicines (SKLNM) and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, PR China.
Nature communications
|December 12, 2025
概括
这项研究引入了一种新的Pd/Cu联合催化反应,用于合成具有高立体控制的复杂桥环化合物. 这些性分子显示出作为cGAS-STING信号通路的抑制剂的潜力.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 催化剂是一种催化剂.
背景情况:
- 桥环支架在制药和天然产品中至关重要.
- 具有多个立体中心的这些紧张结构的enantioselective合成具有挑战性.
研究的目的:
- 开发一种方法,用于基因结合的双循环[3.2.1]octenes和双循环[3.2.1]octanes的酶选择性合成.
- 探索随后的硬性性三环和四环三环的立体特异合成.
- 评估这些化合物在生物应用中的潜力,特别是针对cGAS-STING通路.
主要方法:
- 一种由 (Pd) 和铜 (Cu) 催化的基质依赖的反离子双重Heck/Sonogashira反应.
- 桥环骨的内分子循环化.
- 预先的生物活性测定.
- 机械学研究和密度函数理论 (DFT) 计算.
主要成果:
- 成功合成基连接的 (R,S,S) - 双环[3.2.1]烯和 (S,R,R) - 双环[3.2.1]烯与一个四级和两个相邻的三级立体中心.
- 刚性性三环三和四环四三的立体特异合成.
- 两种合成的性桥环化合物对cGAS-STING信号通路表现出显著的抑制作用.
- DFT计算确定了减小消除作为确定速率的步骤,并阐明了控制基质依赖的反分歧的因素.
结论:
- 开发的Pd/Cu联合催化联反应为复杂的性桥梁环系统提供了有效的途径.
- 合成的化合物是用于进一步化学转换的多功能构建模块.
- 这些已识别的化合物对cGAS-STING等途径的治疗干预具有前景.
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