Alkaloids ofDelphinium speciosum
On separating the total alkaloids we isolated methyllycaconitine, lycoctonine, anthranoyllycoctonine, and gigactonine, which were identified on the basis of an analysis of spectral characteristics and a comparison of the I~C NMR spectra. In addition to these, a base was isolated with mp 180-182°C (acetone), composition C22H35N05 (I). The NMR spectrum of (I) had the signals of tertiary C-methyl group (0.97 ppm, 3 H, singlet), of a N-ethyl group (1.04 ppm, 3 H, triplet, J = 7 Hz), and of a methoxy group (3.82 ppm, 3 H, singlet), and also one-proton signals at 4.12 ppm (triplet, J = 5 Hz) and 4.6 ppm (doublet, J = 7 Hz), The IR spectrum showed the absorption bands of hydroxy groups at 3400-3600 cm -: and of ether bonds at ii00 cm -~. The mass spectrum of (I) was characteristic for alkaloids with the lycoctonine skeleton and was close to the spectrum of karakoline [2, 3]. The maximum peak in the mass spectrum of (I) was the peak of the M +17 ion, showing the presence of the hydroxy group at C-I [2], Acetylation of the alkaloid with acetic anhydride in the presence of pyridine yielded the triacetate (II) with mp 162-164°C (acetone), showing the presence of three secondary hydroxy groups. Its mass spectrum contained the peak of the molecular ion M + 519 (8%), and also the peaks of ions with m/z 476 (8%), 460 (100%), 416 (15%) and 400 (12%), The PMR spectrum contained the signals of a N-ethyl, a tertiary C-methyl, and of three acetoxy groups, and also one-proton signals at 4.68 ppm (triplet, J = 5 Hz), 4.75 ppm (quartet, ABX system, JAX = i0 Hz, JBX = 7 Hz) and 5.22 ppm (doublet, J = 7 Hz), showing the presence of hydroxy groups at C-14, C-I, and C-6 [3, 4]. The acetylation of (I) with acetyl chloride gave the tetraacetate (III). Its mass spectra contained the peak of the molecular ion M + 561 (1%), and also the peaks of ions with m/z 502 (77%), 442 (33%), 400 (100%), and 372 (33%), According to these results, the fourth hydroxy group must be located at C-8, The information obtained indicated that (I) was alkaloid B, isolated previously from Delphinium bicolor Nutt, [4-7]. A direct comparison with alkaloid B kindly supplied by Prof, M. N, Benn showed their identity.
The alkaloids of nutt.
The structures of alkaloid- and - were established via X-ray crystallography of the former as its HI salt, and its chemical conversion to the latter.
Electrophysiological Studies of Penticainide (CM 7857), a New Antiarrhythmic Agent, in Mammalian Myocardium
The intracellular electrophysiologic properties of a new antiarrhythmic substance, penticainide, were studied in isolated rabbit, dog, and guinea pig myocardial preparations superfused or perfused with oxygenated Tyrode's solution. “Therapeutic” concentrations of penticainide (1.5 to 3 x 10-5 M) had little effect on sinus node automaticity; sinoatrial conduction was slightly delayed. In atrial, Purkinje and ventricular fibers, amplitude, and maximal rate of rise of phase 0 (dV/dtmax) were decreased by penticainide; Purkinje-ventricle conduction velocity was depressed. Penticainide did not significantly modify action potential duration (APD) of rabbit atria and dog ventricle and reduced APD and effective refractory period (ERP) of dog Purkinje and guinea pig ventricular fibers. Penticainide reduced APD heterogeneity of Purkinje-ventricle junction with a preferential effect at the gate and decreased tension amplitude of perfused papillary muscle in dog heart. The effect of penticainide on dV/dtmax was voltage and rate dependent; the resting block was weak. Thus, penticainide is a class 1 antiarrhythmic agent with properties of class 1B agents such as APD reduction and properties of class 1C agents such as slow recovery kinetic of rate-dependent block.