title: Constrained Cyclopeptides: Biaryl Formation through Pd-Catalyzed C-H Activation in Peptides-Structural Control of the Cyclization vs. Cyclodimerization Outcome.
abstract: A series of short tryptophan-phenylalanine peptides containing an iodo substituent on the phenyl ring was subjected to Pd-catalyzed CH activation reactions to give the corresponding aryl-indole coupled products. Two types of adducts were generated: cyclomonomer and cyclodimeric peptides; no evidence of oligo- or polymerization products was detected. Contrary to standard peptide macrocyclizations, the factors controlling the fate of the reaction are the number of amino acids between the aromatic residues and the regiochemistry of the parent iodo derivative, independent of both the concentration and the cyclization mode. The method is general and allows access to novel biaryl peptidic topologies, which have been fully characterized.
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10-12, 08028, Barcelona, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Mendive-Tapia
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10-12, 08028, Barcelona, Spain.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bertran
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10-12, 08028, Barcelona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: García
authors.affiliation: CIBER-BBN, Networking Centre in Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac 10-12, 08028, Barcelona, Spain.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Acosta
authors.affiliation: CIBER-BBN, Networking Centre in Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac 10-12, 08028, Barcelona, Spain.|Department of Organic Chemistry, University of Barcelona, Martí i Franqués 1-11, 08028, Barcelona, Spain.|School of Chemistry, University of KwaZulu-Natal, 4001-, Durban, South Africa.
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.affiliation: CIBER-BBN, Networking Centre in Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac 10-12, 08028, Barcelona, Spain. rlavilla@pcb.ub.es.|Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona Science Park, Baldiri Reixac 10-12, 08028, Barcelona, Spain. rlavilla@pcb.ub.es.
authors.forename: Rodolfo
authors.identifier: http://orcid.org/0000-0001-9159-6089
authors.initials: R
authors.lastname: Lavilla
mesh_terms: D002384:Catalysis; D003500:Cyclization; D019281:Dimerization; D007211:Indoles / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry; D011487:Protein Conformation; D014364:Tryptophan / Q000737:chemistry
chemical_list: D007211:Indoles; D010456:Peptides, Cyclic; D010649:Phenylalanine; D010165:Palladium; C030374:indole; D014364:Tryptophan
keywords: C−H activation; biaryls; cyclization; palladium; peptides