title: Synthesis of dragmacidin D via direct C-H couplings.
abstract: Dragmacidin D, an emerging biologically active marine natural product, has attracted attention as a lead compound for treating Parkinson's and Alzheimer's diseases. Prominent structural features of this compound are the two indole-pyrazinone bonds and the presence of a polar aminoimidazole unit. We have established a concise total synthesis of dragmacidin D using direct C-H coupling reactions. Methodological developments include (i) Pd-catalyzed thiophene-indole C-H/C-I coupling, (ii) Pd-catalyzed indole-pyrazine N-oxide C-H/C-H coupling, and (iii) acid-catalyzed indole-pyrazinone C-H/C-H coupling. These regioselective catalytic C-H couplings enabled us to rapidly assemble simple building blocks to construct the core structure of dragmacidin D in a step-economical fashion.
authors.affiliation: Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan.
authors.forename: Debashis
authors.initials: D
authors.lastname: Mandal
authors.forename: Atsushi D
authors.initials: AD
authors.lastname: Yamaguchi
authors.forename: Junichiro
authors.initials: J
authors.lastname: Yamaguchi
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Itami
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D026121:Indole Alkaloids; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D010165:Palladium / Q000737:chemistry; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D011719:Pyrazines / Q000737:chemistry; D013876:Thiophenes / Q000737:chemistry
chemical_list: D001688:Biological Products; D026121:Indole Alkaloids; D007211:Indoles; D010879:Piperazines; D011719:Pyrazines; D013876:Thiophenes; C470335:dragmacidin D; D010165:Palladium; C030374:indole