Aconite alkaloids, structures

Abrine, 484 Abrotine, 772 Abrtis precatorius, 484 Abuta spp., 371 Acacia spp., 771 Acetylcholine, 262, 518 Acetylomithine, 170, 171, 172 Achillea spp., 779 Achilleine achilletine, 779 Acolyctine, 686 Aconine, 673, 675, 679, 685 Aconines, nuclear structure, 693 Aconite alkaloids, 673 Aconitine, 673, 674, 775 oxidation products, 676 Aconitines, pharmacological action, 690 Aconitinone, 676 Aconitoline, 675... 

Research on diterpenoid alkaloids published during the past year has continued to expand the body of structural and synthetic information available on these complex plant bases. The structures of ten new alkaloids from Aconitum and Delphinium species, including seven new bisditerpenoid alkaloids, have been reported. Tlie most significant progress in methods of structure elucidation has been the very successful applications of n.m.r. to the study of complex diterpenoid alkaloids. The New Bruns wick group under Professor Karel Wiesner has continued its progress toward the syntheses of the Ci9-aconitine-type alkaloids. An historical account of the synthesis of talatisamine (1), the first synthesis of a hexacyclic aconite alkaloid, has been published. This work was reviewed in a previous Report. ... 

Figure 1. Structures of aconite alkaloids investigated. Copyright 1986 American Cyanamid Co. Reprinted with permission.

Research studies on the aconite alkaloids started at the beginning of the nineteenth century, and aconitine was isolated from Actinidia napellus in 1833. As for the Aconitum plants of Japan, Shimoyama made the first report in 1882, and the plain chemical structure of aconitine was reported in the 1950s [4]. The stereochemistry, including absolute configuration, of the aconitine skeleton was determined when the total synthesis delphinine, an aconitine-related alkaloid, was achieved in 1972 [5-7]. 

K. Wiesner, Some Highlights in the Structural and Synthetic Chemistry of the Aconite Alkaloids. A Personal Historical Perspective, Tetrahedron, 1985, 4 , 485. 

The overall transformation of the atisane skeleton e.g. atiserene, 274) to the Ci9 aconite alkaloids, apart from oxidative and functionalization steps, requires three principal structural alterations C7-C20 bond connection, removal of one carbon (C17), and rearrangement of the Cg-Cg bond to C15. Although the order of these alterations is not known, the isolation of the atisine-type alkaloid, denudatin (285), which possesses the C7-C20 link, indicates that this step may occur first. 

This kind of reaction was first recorded for aconitine (p. 675) and it serves to emphasise the parallelism in reactivity, and probably therefore in structure, which exists between aconitine and delphinine and possibly between the whole range of aconite and larkspur alkaloids. 

The most toxic alkaloids of aconite, such as aconitine, mesaconitine, hypaconitine, etc., are known to possess arrhythmogenic effect. Aconitine itself has long been used to induce arrhythmia in experimental models [38, 39]. Aconitine and its structural analogues induce ventricular ectopics, ventricular tachycardia, torsades de pointes, and ventricular fibrillation in a dose-dependent manner. Aconitine has a positive inotropic effect on the heart. It has hypotensive and bradycardic actions [40]. Another group of diterpenoid alkaloids possessing C18 and C19 skeleton, such as lappaconitine, A -deacetyllappac(Miitine, heteratisine, and 6-benzoylheteratisine, are... 

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