Semisynthesis and myocardial activity of thaliporphine N-homologues

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.