Issue 10, 2015

Mechanistic investigation of aziridine aldehyde-driven peptide macrocyclization: the imidoanhydride pathway

Abstract

Aziridine aldehyde dimers, peptides, and isocyanides participate in a multicomponent reaction to yield peptide macrocycles. We have investigated the selectivity and kinetics of this process and performed a detailed analysis of its chemoselectivity. While the reactants encompass all of the elements of the traditional Ugi four-component condensation, there is a significant deviation from the previously proposed mechanism. Our results provide evidence for an imidoanhydride pathway in peptide macrocyclization and lend justification for the diastereoselectivity and high effective molarity observed in the reaction.

Graphical abstract: Mechanistic investigation of aziridine aldehyde-driven peptide macrocyclization: the imidoanhydride pathway

Supplementary files

Article information

Article type
Edge Article
Submitted
01 Jun 2015
Accepted
07 Jul 2015
First published
07 Jul 2015
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2015,6, 5446-5455

Mechanistic investigation of aziridine aldehyde-driven peptide macrocyclization: the imidoanhydride pathway

S. Zaretsky, J. L. Hickey, J. Tan, D. Pichugin, M. A. St. Denis, S. Ler, B. K. W. Chung, C. C. G. Scully and A. K. Yudin, Chem. Sci., 2015, 6, 5446 DOI: 10.1039/C5SC01958C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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