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Updated: Jun 13, 2026

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Preparation and use of cysteine orthoesters for solid-supported synthesis of peptides
Zedu Huang1, Darren J Derksen, John C Vederas
1Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
Abstract:
Synthesis of a chiral cysteine derivative 2 with the carboxyl protected by an acid-labile 4-methyl-2,6,7-trioxabicyclo[2.2.2]octyl (OBO) orthoester is reported. A disulfide anchoring strategy is used to link the sulfur of this OBO cysteine derivative onto modified trityl polystyrene resin for synthesis of peptides having C-terminal cysteine (Cys) residues. Fmoc-based solid phase peptide synthesis affords model tripeptides without significant epimerization. The approach is used to make the orally active analgesic crotalphine and its Cys1 diastereomer.
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