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Updated: Aug 6, 2026

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Sandwich-SuFEx Cyclization Enables One-Pot Synthesis of Multicyclic Peptides with Tunable Topologies
Tianxiong Mi1, Lijun Fan1, Erwin G Abucayon2
1Discovery Chemistry, Merck & Co., Inc., Rahway, New Jersey07065, United States.
Abstract:
Sandwich-SuFEx (sulfur(VI) fluoride exchange) cyclization is introduced as a rapid, aqueous cross-linking reaction complementary to CuAAC and thioether formation. Di- or triarmed aryl sulfonyl fluorides selectively capture peptide phenols to afford terphenyl-bridged macrocycles spanning 5- to 12-mers, tolerating diverse side chains and linker designs. One-pot reactions combining sandwich-SuFEx with thioether formation assemble bi-, tri-, and tetracyclic peptides with tunable topologies in <1 h, expanding the toolbox for aqueous multicycle assembly.
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