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Updated: Feb 8, 2026

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine
Published on: June 13, 2022
A Mechanistic Model for the Aziridine Aldehyde-Driven Macrocyclization of Peptides
Lee Belding1, Serge Zaretsky2, Andrei K Yudin2
1Department of Chemistry , Brock University , St. Catharines , Ontario L2S 3A1 , Canada.
Abstract:
Aziridine aldehyde-driven macrocyclization of peptides is a powerful tool for the construction of biologically active macrocycles. While this process has been used to generate diverse collections of cyclic molecules, its mechanistic underpinnings have remained unclear. To enable progress in this area we have carried out a mechanistic study, which suggests that the cyclization owes its efficiency to a combination of electrostatic attraction between the termini of a nitrilium ion intermediate and intramolecular hydrogen bonding. Our model adequately explains the experimentally observed trends, including diastereoselectivity, and should facilitate the development of other macrocyclization reactions.
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