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Updated: Aug 22, 2025

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Single Atom Ring Contraction of Peptide Macrocycles Using Cornforth Rearrangement
Sungjoon Huh1, George J Saunders1, Andrei K Yudin1
1Davenport Research Laboratories, University of Toronto, 80 St. George St, Toronto, Ontario, M5S 3H6, Canada.
Abstract:
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.
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