Issue 2, 2015

Bidirectional macrocyclization of peptides by double multicomponent reactions

Abstract

Increasing the diversity of peptide cyclization methods is an effective way of accessing new types of macrocyclic chemotypes featuring a wide variety of ring sizes and topologies. Multicomponent reactions (MCRs) are processes capable of generating great levels of molecular diversity and complexity at low synthetic cost. In an attempt to further exploit MCRs in the field of cyclopeptides, we describe a bidirectional multicomponent approach for the synthesis of N-alkylated macrocyclic peptides of varied sequences and cross-linking positions. The process relies on the execution of two Ugi reactions between peptide diacids and diisocyanides. Varying the amino component enabled the installation of exocyclic elements of diversity, while skeletal diversity was created through different side chain and backbone cyclizations. This procedure shows prospects for the rapid scanning of the chemical space of macrocyclic peptides for applications in chemical biology and drug discovery.

Graphical abstract: Bidirectional macrocyclization of peptides by double multicomponent reactions

Supplementary files

Article information

Article type
Paper
Submitted
09 Sep 2014
Accepted
09 Oct 2014
First published
14 Oct 2014

Org. Biomol. Chem., 2015,13, 438-446

Author version available

Bidirectional macrocyclization of peptides by double multicomponent reactions

M. G. Ricardo, F. E. Morales, H. Garay, O. Reyes, D. Vasilev, L. A. Wessjohann and D. G. Rivera, Org. Biomol. Chem., 2015, 13, 438 DOI: 10.1039/C4OB01915F

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