Semisynthesis and myocardial activity of thaliporphine N-homologues

Chi Ming Chiou, Chin Ting Lin, Wei Jang Huang, Yu Mei Chang, Yi Jin Ho, Ming Jai Su, Shoei Sheng Lee

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7 Citations (Scopus)

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. 1H 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.

Original languageEnglish
Pages (from-to)405-412
Number of pages8
JournalJournal of Natural Products
Volume76
Issue number3
DOIs
Publication statusPublished - Mar 22 2013

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ASJC Scopus subject areas

  • Complementary and alternative medicine
  • Molecular Medicine
  • Organic Chemistry
  • Analytical Chemistry
  • Pharmaceutical Science
  • Pharmacology
  • Drug Discovery

Cite this

Chiou, C. M., Lin, C. T., Huang, W. J., Chang, Y. M., Ho, Y. J., Su, M. J., & Lee, S. S. (2013). Semisynthesis and myocardial activity of thaliporphine N-homologues. Journal of Natural Products, 76(3), 405-412. https://doi.org/10.1021/np3007765