title: Diversity-Oriented Synthesis of Coumarin-Linked Benzimidazoles via a One-Pot, Three-Step, Intramolecular Knoevenagel Cyclization.
abstract: Diversity-oriented synthesis of coumarin-linked benzimidazoles from N-(2-aminophenyl)-2-cyanoacetamide was achieved via a one-pot, three-step sequential reaction in excellent yields. In situ intramolecular cyclization of the cyanoacetamide afforded benzimidazoles which subsequently underwent a Knoevenagel condensation of the 2-cyanomethylbenzimidazoles with salicylaldehydes promoted by triethylamine to reach the target compounds. An important intermediate, 2-(2-imino-2H-chromen-3-yl)-1H-benzimidazole was characterized by X-ray analysis and further hydrolyzed to 2-(coumarin-3-yl)benzimidazole in acidic condition. Among the synthesized compounds, some were found to be promising inhibitors of porcine kidney d-amino acid oxidase (pkDAO).
authors.affiliation: Department of Applied Chemistry, National Chiao-Tung University , Hsinchu 300-10, Taiwan.
authors.forename: Po-Hsin Eric
authors.initials: PE
authors.lastname: Yao
authors.affiliation: Department of Applied Chemistry, National Chiao-Tung University , Hsinchu 300-10, Taiwan.
authors.forename: Sunil
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes , Miaoli, Taiwan.
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes , Miaoli, Taiwan.
authors.forename: Chiu-Ping
authors.initials: CP
authors.lastname: Fang
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes , Miaoli, Taiwan.
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Department of Applied Chemistry, National Chiao-Tung University , Hsinchu 300-10, Taiwan.|Department of Medicinal and Applied Chemistry, Kaohsiung Medical University , 100 Shih-Chuan 1stRoad, Kaohsiung 807-08, Taiwan.
authors.forename: Chung-Ming
authors.identifier: 0000-0002-1804-1578
authors.initials: CM
authors.lastname: Sun
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis*; D020650:Combinatorial Chemistry Techniques; D003374:Coumarins / Q000138:chemical synthesis*; D003500:Cyclization; D003605:D-Amino-Acid Oxidase / Q000037:antagonists & inhibitors / Q000737:chemistry; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry; D013552:Swine
chemical_list: D000447:Aldehydes; D001562:Benzimidazoles; D003374:Coumarins; D009570:Nitriles; C013243:salicylaldehyde; D003605:D-Amino-Acid Oxidase; C031594:2-cyanoacetamide
keywords: Knoevenagel condensation; coumarin; diversity-oriented synthesis; one-pot synthesis; pkDAO activity