Jörn Saupe; Oliver Kunz; Lars Ole Haustedt; Sven Jakupovic; Christian Mang
Chem. Eur. J., 2017, 23, 11784-11791
https://doi.org/10.1002/chem.201703209

Abstract

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. We have developed an efficient method for the generation of novel macrocyclic peptidebased scaffolds. The process, which we called MacroEvoLution, is based on a cyclization screening approach which 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 on 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