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.

Cytotoxic Alkaloids from the Stem of Xylopia laevigata

“…Phytochemical analysis of the stem of X. laevigata resulted in the isolation of 19 alkaloids, including 11 aporphines, namely, (−)-oemerine [8], (+)-anonaine [9], (+)-glaucine [10], (+)-xylopine [11], (+)-norglaucine [12], asimilobine [9], (+)-norpurpureine [13], (+)- N -methyllaurotetanine [14], (+)-norpredicentrine [15], (+)-calycinine [16] and (+)-laurotetanine [7]; two oxoaporphines, namely, lanuginosine [17] and oxoglaucine [18]; four tetrahydroprotoberberinic alkaloids, namely, (−)-xylopinine [11], (+)-discretine [7], (−)-corytenchine [11] and (+)-discretamine [9]; one benziltetrahydroisoquinoline, namely, (+)-reticuline [19]; and one morphinandienone, namely, (+)-flavinantine [20]. The chemical structures are presented in Figure 1.…”

Recent Advances for the C–C and C–N Bond Formation in the Synthesis­ of 1-Phenethyl-tetrahydroisoquinoline, Aporphine, Homoaporphine­, and β-Carboline Alkaloids

“…Laurolitsine (31) was isolated from the leaves of Peumus boldus Molina in 0.001% 55 Based on the biosynthesis of aporphine alkaloids, Lee and co-workers 56 transformed laurolitsine (31) into a series of aporphine alkaloids 34-37. Beginning with N-protection and followed by O-methylation, the intermediate 33 was subjected to treatment with strong acid for an extended period (8 days) in order to produce pacordine (34), an alkaloid found in Popowia pisocarpa, an Annonaceous plant.…”

“…Screening of 36 against myo- cardial activity on rat cardiac tissues revealed potent positive inotropic, but a slightly negative chronotropic effect, indicating the potent antiarrhythmic activity of 36 (Scheme 6). 56 (+)-Boldine (38) was transformed into the C9 alkoxy analogue, N-methyllaurotetanine (39), which was then used as a starting material for the preparation of the O-alkylated products 40 through a Mitsunobu reaction. This generated a small library of derivatives that displayed moderate selectivity against 5-HT 1A and 5-HT 2A receptors, indicating that this kind of O-substitution is not critical for the affinity to these receptors (Scheme 7).…”