Two-Step Synthesis of Complex Artificial Macrocyclic Compounds

Rudrakshula Madhavachary, Eman M.M. Abdelraheem, Arianna Rossetti, Aleksandra Twarda-Clapa, Bogdan Musielak, Katarzyna Kurpiewska, Justyna Kalinowska-Tłuścik, Tad A. Holak, Alexander Dömling*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

32 Citations (Scopus)


The design and synthesis of head-to-tail linked artificial macrocycles using the Ugi-reaction has been developed. This synthetic approach of just two steps is unprecedented, short, efficient and works over a wide range of medium (8–11) and macrocyclic (≥12) loop sizes. The substrate scope and functional group tolerance is exceptional. Using this approach, we have synthesized 39 novel macrocycles by two or even one single synthetic operation. The properties of our macrocycles are discussed with respect to their potential to bind to biological targets that are not druggable by conventional, drug-like compounds. As an application of these artificial macrocycles we highlight potent p53–MDM2 antagonism.

Original languageEnglish
Pages (from-to)10725-10729
Number of pages5
JournalAngewandte Chemie - International Edition
Issue number36
Early online date10 Jul 2017
Publication statusPublished - 23 Aug 2017


  • drug discovery
  • macrocycles
  • protein–protein interactions
  • synthetic methods
  • Ugi reaction


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