title: Preparation and use of cysteine orthoesters for solid-supported synthesis of peptides.
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.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
authors.forename: Zedu
authors.initials: Z
authors.lastname: Huang
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Derksen
authors.forename: John C
authors.initials: JC
authors.lastname: Vederas
mesh_terms: D003545:Cysteine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry*; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D004952:Esters; D010455:Peptides; D003545:Cysteine