title: Application of Negishi cross-coupling to the synthesis of the cyclic tripeptides OF4949-III and K-13.
abstract: Syntheses of the cyclic tripeptides OF4949-III 1 and K-13 2 are reported, in which the key steps are intermolecular and intramolecular Negishi cross-coupling reactions, respectively. In addition, the synthesis of a protected isomer of K-13 25 is reported. The synthesis of K-13 features a tripeptidic organozinc reagent 11, one of the most highly functionalized such reagents to be described. An O-aryltyrosine derivative 15, prepared by S(N)Ar reaction between Boc-tyrosine and 2-fluorobenzaldehyde, followed by Dakin reaction, iodination, and methylation, is used as a common intermediate for all of the syntheses described. The routes to this class of cyclic tripeptide are among the shortest reported to date and demonstrate the high functional group tolerance of the carbon-zinc bond toward peptide derivatives.
authors.affiliation: Department of Chemistry, The University of Sheffield, Dainton Building, Sheffield S3 7HF, United Kingdom.
authors.forename: Luca
authors.initials: L
authors.lastname: Nolasco
authors.forename: Manuel
authors.initials: M
authors.lastname: Perez Gonzalez
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Caggiano
authors.forename: Richard F W
authors.initials: RF
authors.lastname: Jackson
mesh_terms: D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis*; D010456:Peptides, Cyclic / Q000138:chemical synthesis*
chemical_list: D009842:Oligopeptides; D010456:Peptides, Cyclic