title: Bioorthogonal Diversification of Peptides through Selective Ruthenium(II)-Catalyzed C-H Activation.
abstract: Methods for the chemoselective modification of amino acids and peptides are powerful techniques in biomolecular chemistry. Among other applications, they enable the total synthesis of artificial peptides. In recent years, significant momentum has been gained by exploiting palladium-catalyzed cross-coupling for peptide modification. Despite major advances, the prefunctionalization elements on the coupling partners translate into undesired byproduct formation and lengthy synthetic operations. In sharp contrast, we herein illustrate the unprecedented use of versatile ruthenium(II)carboxylate catalysis for the step-economical late-stage diversification of α- and β-amino acids, as well as peptides, through chemo-selective C-H arylation under racemization-free reaction conditions. The ligand-accelerated C-H activation strategy proved water-tolerant and set the stage for direct fluorescence labelling as well as various modes of peptide ligation with excellent levels of positional selectivity in a bioorthogonal fashion. The synthetic utility of our approach is further demonstrated by twofold C-H arylations for the complexity-increasing assembly of artificial peptides within a multicatalytic C-H activation manifold.
authors.affiliation: Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, 37077, Göttingen, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schischko
authors.affiliation: Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, 37077, Göttingen, Germany.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Ren
authors.affiliation: Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, 37077, Göttingen, Germany.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kaplaneris
authors.affiliation: Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, 37077, Göttingen, Germany.
authors.forename: Lutz
authors.identifier: 0000-0001-7034-8772
authors.initials: L
authors.lastname: Ackermann
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D002384:Catalysis; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D002264:Carboxylic Acids; D005456:Fluorescent Dyes; D006841:Hydrocarbons, Aromatic; D010455:Peptides; D010165:Palladium; D012428:Ruthenium; D006859:Hydrogen
keywords: C−H activation; labeling; ligation; peptides; ruthenium