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Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine
Published on: June 13, 2022
Diversity-Oriented Synthesis of Cyclic Azapeptides by A3 -Macrocyclization Provides High-Affinity CD36-Modulating
Jinqiang Zhang1,2, Mukandila Mulumba3, Huy Ong3
1Département de Chimie, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, Québec, H3C 3J7, Canada.
Abstract:
Macrocyclization has enabled the use of peptides in drug discovery creating a need for methods to synthesize diverse peptide macrocycles. Azapeptides have advanced to clinically used drugs, however, few cyclic azapeptides have been studied. A multiple component "A3 -macrocyclization" strategy is described for the preparation of diverse cyclic azapeptides and is demonstrated by the synthesis of 15 growth hormone releasing hormone-6 (GHRP-6) analogs. Certain cyclic aza-GHRP-6 analogs exhibited unprecedented affinity for the CD36 receptor, and capacity to modulate Toll-like receptor agonist-induced overproduction of nitric oxide, and reduce pro-inflammatory cytokine and chemokine production in macrophages.
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