Preparation and use of cysteine orthoesters for solid-supported synthesis of peptides

Zedu Huang; Darren J Derksen; John C Vederas

doi:10.1021/ol100645t

Preparation and use of cysteine orthoesters for solid-supported synthesis of peptides

Org Lett. 2010 May 21;12(10):2282-5. doi: 10.1021/ol100645t.

Authors

Zedu Huang¹, Darren J Derksen, John C Vederas

Affiliation

¹ Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.

PMID: 20405951
DOI: 10.1021/ol100645t

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cysteine / analogs & derivatives
Cysteine / chemical synthesis*
Cysteine / chemistry*
Esters / chemical synthesis*
Esters / chemistry*
Molecular Structure
Peptides / chemical synthesis*
Peptides / chemistry
Stereoisomerism

Substances

Esters
Peptides
Cysteine