Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226 001, India.
J Org Chem. 2012 Feb 3;77(3):1414-21. doi: 10.1021/jo202255v. Epub 2012 Jan 24.
Several diversity-oriented syntheses of N-fused polycyclic heterocycles have been demonstrated but most of them are based on point diversity within the same library and usually involve time-consuming sequential multistep syntheses, which also suffer from low yields and/or poor precursor scopes. We have developed a new strategy for the syntheses of skeletal diverse N-fused polycyclic compounds via an Ugi-type MCR followed by a CuI-catalyzed coupling reaction or tandem Pictet-Spengler reaction. This two-step sequence provides eight distinct skeleton of fused {6-5-5-6}, {5-5-5-6}, {6-5-6-6}, and {5-5-6-6} ring systems that have applications in medicinal chemistry and chemical genetics too.
已经有几种基于导向的方法可以用来合成 N-稠合的多环杂环化合物，但是大多数方法都是基于同一文库内的点多样性，而且通常涉及耗时的顺序多步合成，这也导致了低收率和/或较差的前体范围。我们开发了一种新的策略，通过 Ugi 型 MCR 随后进行 CuI 催化偶联反应或串联 Pictet-Spengler 反应，来合成骨架多样的 N-稠合多环化合物。这个两步序列提供了八种不同骨架的稠合{6-5-5-6}、{5-5-5-6}、{6-5-6-6}和{5-5-6-6}环系，这些环系在药物化学和化学生物学中也有应用。
