Single Atom Ring Contraction of Peptide Macrocycles Using Cornforth Rearrangement

Autor: Sungjoon Huh, George J. Saunders, Andrei K. Yudin
Rok vydání: 2022
Předmět:
Zdroj: Angewandte Chemie International Edition. 62
ISSN: 1521-3773
1433-7851
DOI: 10.1002/anie.202214729
Popis: Site-selective transformations of densely functionalized scaffolds have been a topic of intense interest in chemical synthesis. Herein we have repurposed the rarely used Cornforth rearrangement as a tool to effect a single-atom ring contraction in cyclic peptide backbones. Investigations into the kinetics of the rearrangement were carried out to understand the impact of electronic factors, ring size, and linker type on the reaction efficiency. Conformational analysis was undertaken and showed how subtle differences in the peptide backbone result in substrate-dependent reaction profiles. This methodology can now be used to perform conformation-activity studies. The chemistry also offers an opportunity to install building blocks that are not compatible with traditional C-to-N iterative synthesis of macrocycle precursors.
Databáze: OpenAIRE
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