Saupe Jörn, Kunz Oliver, Haustedt Lars Ole, Jakupovic Sven, Mang Christian
AnalytiCon Discovery GmbH, Hermannswerder Haus 17, 14473, Potsdam, Germany.
Chemistry. 2017 Sep 4;23(49):11784-11791. doi: 10.1002/chem.201703209. Epub 2017 Aug 7.
Macrocycles are a structural class bearing great promise for future challenges in medicinal chemistry. Nevertheless, there are few flexible approaches for the rapid generation of structurally diverse macrocyclic compound collections. Here, an efficient method for the generation of novel macrocyclic peptide-based scaffolds is reported. The process, named here as "MacroEvoLution", is based on a cyclization screening approach that gives reliable access to novel macrocyclic architectures. Classification of building blocks into specific pools ensures that scaffolds with orthogonally addressable functionalities are generated, which can easily be used for the generation of structurally diverse compound libraries. The method grants rapid access to novel scaffolds with scalable synthesis (multi gram scale) and the introduction of further diversity at a late stage. Despite being developed for peptidic systems, the approach can easily be extended for the synthesis of systems with a decreased peptidic character.
大环化合物是一类在药物化学未来面临的挑战中极具潜力的结构类型。然而，用于快速生成结构多样的大环化合物库的灵活方法却很少。在此，报道了一种生成新型大环肽基支架的有效方法。该过程在此命名为“大环进化”，基于一种环化筛选方法，可可靠地获得新型大环结构。将构建模块分类到特定库中可确保生成具有可正交寻址功能的支架，这些支架可轻松用于生成结构多样的化合物库。该方法可通过可扩展合成（多克规模）快速获得新型支架，并在后期引入更多样性。尽管该方法是为肽类系统开发的，但可轻松扩展用于合成肽性特征降低的系统。
