Solid-Phase Parallel Synthesis of Functionalised Medium-to-Large Cyclic Peptidomimetics through Three-Component Coupling Driven by Aziridine Aldehyde Dimers

• Published in: Chemistry : a European journal Vol. 21; no. 25; pp. 9249 - 9255
• Main Authors: Treder, Adam P., Hickey, Jennifer L., Tremblay, Marie-Claude J., Zaretsky, Serge, Scully, Conor C. G., Mancuso, John, Doucet, Annie, Yudin, Andrei K., Marsault, Eric
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 15.06.2015; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Aldehydes; Chemistry; Chemistry, Multidisciplinary; Dimers; drug discovery; Joining; macrocycles; Peptides; Physical Sciences; Science & Technology; small ring systems; solid-phase synthesis; Synthesis; MULTICOMPONENT REACTIONS; drug discovery; MACROCYCLIC PEPTIDES; macrocycles; small ring systems; PIPERAZINONES; LIBRARY; peptides; solid-phase synthesis; STRATEGIES
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201500068

The first solid‐phase parallel synthesis of macrocyclic peptides using three‐component coupling driven by aziridine aldehyde dimers is described. The method supports the synthesis of 9‐ to 18‐membered aziridine‐containing macrocycles, which are then functionalized by nucleophilic opening of the aziridine ring. This constitutes a robust approach for the rapid parallel synthesis of macrocyclic peptides. Solid‐phase macrocycles: The first solid‐phase parallel synthesis of macrocyclic peptides using three‐component coupling driven by aziridine aldehyde dimers is described. The method supports the synthesis of 9‐ to 18‐membered aziridine‐containing macrocycles, which are then functionalised by nucleophilic opening of the aziridine ring (see scheme). This constitutes a robust approach for the rapid parallel synthesis of macrocyclic peptides.