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Updated: Dec 10, 2025

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Synthesis and Diversification of Macrocyclic Alkynediyl Sulfide Peptides
Éric Godin1, Sacha Nguyen Thanh1, Javier Guerrero-Morales1
1Département de Chimie, Centre for Green Chemistry and Catalysis, Université de Montréal, Complexe des Sciences, 1375 Avenue Thérèse-Lavoie-Roux, Montréal, Québec, H2V 0B3, Canada.
Abstract:
The synthesis of rare macrocyclic alkynediyl sulfides by a Cu-catalyzed Csp -S cross-coupling is presented. The catalytic protocol (Cu(MeCN)4 PF6 /dtbbpy) promotes macrocyclization of peptides, dipeptides and tripeptides at ambient temperature (14 examples, 23→73 % yields) via thiols and bromoalkynes, and is chemoselective with regards to terminal alkynes. Importantly, the underexplored alkynediyl sulfide functionality incorporates a rigidifying structural element and opens new opportunities for diversification of macrocyclic frameworks through S oxidation, halide addition and azide-alkyne cycloaddition chemistries to integrate sulfones, halides or valuable fluorophores (7 examples, 37→92 % yields).
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