title: Semisynthesis and myocardial activity of thaliporphine N-homologues.
abstract: The N-homologues and optical isomers of thaliporphine (5a), a potent antiarrhythmic agent, were prepared starting from laurolitsine (1), an abundant aporphine present in Phoebe formosana. Treating N-propylnorglaucine with 90% H2SO4 yielded one additional product, an 11-sulfonyl-1,11-anhydroaporphine. Reaction of N-formylnorglaucine (3a) with 90% H2SO4, however, yielded the 9-sulfonyl-seco product as a major product. Treatment of 3a with 98% H2SO4 yielded pancordine (10), which, upon catalytic hydrogenation, yielded (±)-wilsonirine. (1)H NMR spectroscopic analysis was applied successfully to monitor the optical purity of the crystalline salt while undertaking optical resolution. Thaliporphine (5a) was demonstrated to possess better positive inotropic and less negative chronotropic effects than the left-hand optical isomer and showed the best activity on rat cardiac tissue among the N-homologues prepared.
authors.affiliation: School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10051, Taiwan, Republic of China.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Chiou
authors.forename: Chin-Ting
authors.initials: CT
authors.lastname: Lin
authors.forename: Wei-Jang
authors.initials: WJ
authors.lastname: Huang
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Chang
authors.forename: Yi-Jin
authors.initials: YJ
authors.lastname: Ho
authors.forename: Ming-Jai
authors.initials: MJ
authors.lastname: Su
authors.forename: Shoei-Sheng
authors.initials: SS
authors.lastname: Lee
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001060:Aporphines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D051381:Rats; D013237:Stereoisomerism
chemical_list: D000889:Anti-Arrhythmia Agents; D001060:Aporphines; C080702:thaliporphine; C109133:laurolitsine