title: Palladium-Mediated Arylation of Lysine in Unprotected Peptides.
abstract: A mild method for the arylation of lysine in an unprotected peptide is presented. In the presence of a preformed biarylphosphine-supported palladium(II)-aryl complex and a weak base, lysine amino groups underwent C-N bond formation at room temperature. The process generally exhibited high selectivity for lysine over other amino acids containing nucleophilic side chains and was applicable to the conjugation of a variety of organic compounds, including complex drug molecules, with an array of peptides. Finally, this method was also successfully applied to the formation of cyclic peptides by macrocyclization.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
authors.forename: Hong Geun
authors.initials: HG
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lautrette
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Pentelute
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Buchwald
mesh_terms: D003500:Cyclization; D008239:Lysine / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D009942:Organometallic Compounds; D010456:Peptides, Cyclic; D010165:Palladium; D008239:Lysine
keywords: bioconjugation; chemoselectivity; cross-coupling; peptide macrocyclization; phosphane ligands