Preparation and use of cysteine orthoesters for solid-supported synthesis of peptides.
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.
Huang
Zedu
Z
Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
Derksen
Darren J
DJ
Vederas
John C
JC
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
D004952:Esters; D010455:Peptides; D003545:Cysteine