title: Regioselective copper-catalyzed N(1)-(hetero)arylation of protected histidine.
abstract: We report regioselective N(1)-arylation of protected histidine using copper(i) iodide as a catalyst, trans-N,N'-dimethylcyclohexane-1,2-diamine as a ligand and readily available aryl iodides as coupling partners under microwave irradiation at 130 °C for 40 min. The reaction provides rapid access to electron-donating, electron-withdrawing and bulky group substituted N-arylated histidines in high yields, including previously inaccessible N-heteroaryl histidines. These N(1)-(hetero)aryl histidines are promising building blocks in peptide-based drug design and discovery.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S. A. S. Nagar, Punjab 160 062, India. rahuljain@niper.ac.in.
authors.forename: Krishna K
authors.initials: KK
authors.lastname: Sharma
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S. A. S. Nagar, Punjab 160 062, India. rahuljain@niper.ac.in.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Mandloi
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S. A. S. Nagar, Punjab 160 062, India. rahuljain@niper.ac.in.
authors.forename: Rahul
authors.initials: R
authors.lastname: Jain
mesh_terms: D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000737:chemistry; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry; D015195:Drug Design; D006639:Histidine / Q000138:chemical synthesis / Q000737:chemistry*; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis / Q000737:chemistry*; D007454:Iodides / Q000737:chemistry; D008872:Microwaves; D013237:Stereoisomerism
chemical_list: D003510:Cyclohexanes; D003959:Diamines; D006841:Hydrocarbons, Aromatic; D007454:Iodides; D006639:Histidine; C068558:1,2-dimethylcyclohexane; D003300:Copper