No abstract

The cardiac effect of thirty-eight diterpenoid alkaloids was evaluated on the isolated bullfrog heart model. Among them, twelve compounds exhibited appreciable cardiac activity, with compounds 3 and 35 being more active than the reference drug lanatoside. The structure-cardiac activity relationships of the diterpenoid alkaloids were summarized based on our present and previous studies [2]: i) 1-OMe or 1-OH, 8-OH, 14-OH, and NH (or NMe) are key structural features important for the cardiac effect of the aconitine-type C 19-diterpenoid alkaloids without any esters. C 18-diterpenoid alkaloids, lycoctoninetype C 19-diterpenoid alkaloids, and the veatchine-and denudatine-type C 20-diterpenoid alkaloids did not show any cardiac activity; ii) the presence of 3-OH is beneficial to the cardiac activity; iii) the effect on the cardiac action of 6-OMe, 13-OH, 15-OH, and 16-demethoxy or a double bond between C-15 and C-16 depends on the substituent pattern on the nitrogen atom.

On the basis of intensive interpretation of the 1 H NMR spectroscopic data, the ring A conformation of aconine (1) was speculated as twist boat in CDCl 3 , and as chair or twist boat in acetone-d 6 and pyridine-d 5. The ring A of pseudaconine (2) adopts the chair conformation in CDCl 3 , acetone-d 6 , and pyridine-d 5. Accordingly, the boat conformation of ring A in these two diterpenoid alkaloids in CDCl 3 reported in the literature [1] should be revised. The difference in 13 C NMR data for the same compound (1 or 2) in two different solvents (CDCl 3 , pyridine-d 5) can be attributed to solvent effects.