Lycoctonine

Aconitum lycoctonum. From the roots of this species Hiibschmann isolated the amorphous alkaloids acolyctine and lycoctonine. Dragen-dorff and Spohn showed that Hiibschmann s alkaloids were probably decomposition products of lycaconitine, C2,H3403N2. 2H2O, which they isolated along with myoctonine, 27 30 8 2 - 5H2O. These results liave been considerably extended by Schulze and Bierling, and more recently by Marion and Manske, for lycoctonine. 

Lycoctonine is also the basic, hydrolytic product of some delphinium alkaloids (pp. 694-6). 

A third unnamed base distinguished by giving an insoluble thiocyanate is present on hydrolysis by alkalis it also yields lycoctonine and lycoctonic acid. 

Delphinium ajacis L. From the seed of this species Keller and Volker isolated two crystalline alkaloids which they named ajacine and ajaconine. Their work was reviewed by Hunter, who reported the presence of four alkaloids, viz., ajacine, ajaconine and new alkaloids ajacinine and ajaci-noidine (amorphous). Goodson described ajacine in detail (1944) and later reported the isolation of ajaconine and three more bases distinguished as B, C and D. According to Hunter, lycoctonine (p. 686) is probably also present. 

D. consolida, L. From this species Keller isolated three alkaloids of which one (Base A ) was well defined. Markwood obtained three crystalline alkaloids of which delcosine was probably Keller s base A, and Cionga and Iliescu have added to Markwood s observations, but failed to obtain his third base. This work has recently been critically revised by Marion and Edwards, ( > who have isolated from the seeds six alkaloids of which two, delcosine and delsoline, were already known another, consolidine, may be Markwood s third base, and the remaining three are new records for this species, viz. delsonine, lycoctonine and anthranoyllycoctonine. They have also altered the empirical formulas of the alkaloids delcosine and delsoline. 

Sultankhodzhaev et al. (2005) reported tyrosinase inhibition studies on 15 diterpenoid alkaloids with the lycoctonine skeleton, and their semisynthetic... 

Lycoctonine (6) death occur in mice from respiratory paralysis, by loss of motor control and convulsions [15]. 

The roots of the same plant has yielded one new alkaloid together with two known compounds lycoctonine and lappaconitine. The structure of the new alkaloid (cochlearenine) (11) is quite similar to that of cochleareine (9). Due to this resemblance the stracture determination of the compound 11 was carried out not only by spectral data but also by single-crystal x-ray diffraction studies [19]. 

The last Delphinium species we have investigated was D. linearilobum (Trautv.) N.Busch [20], from this plant we have isolated six known and two new compounds. The knownalkaloids were lycoctonine, 14-acetyltalatisamine,browniine,cammaconine, talatisamine and cochlearenine, the new alkaloids were named as linearilobin (12) and linearilin (13). 

The compound has a lycoctonine type stmcture. It has six degrees of unsaturation which accounted for its skeleton. The spectral data of linearilin is given in Table 4.5. 

The antioxidant activity of the alkaloids (linearilobin, lycoctonine, 14-acetyl-talatizamine, browniine, cammaconine, talatizamine and cochlearenine) of D. linearilobum was performed by DPPH [21] and by metal chelating activity [22] assays cochlearenine and lycoctonine showed high activity (Figs. 4.3 and 4.4). 

The numbering systems for the aconitine, lycoctonine, atisine, and veatchine skeletons are presented in structures A, B, C, and D, respectively. This Report surveys the work reported in the literature that was available in our libraries up to July 1980. 

Studies of the arrhythmogenic effects and the effects on heart rate of aconitine (14), X-desacetyl-lappaconitine (7), lappaconitine (6), lycoctonal (13), lycoctonine (12), lappaconine (15), avadharidine (9), lycaconitine (10), anthranoyl-lycoctonine (8), and cashmiradelphine (septentriodine) (11) were also reported.8 The alkaloids (6), (7), and (15) were found to be arrhythmogenic... 

At the time of its first preparation, it was suggested that efs-inositol might be the only known compound with three axial oxygen atoms attached to one side of the cyclohexane ring. However, there are two natural compounds which—if the structures at present allocated to them are correct— contain the same arrangement, namely, ouabagenin160 and lycoctonin.161... 

On reduction, spireine afforded di- and tetrahydro derivatives. The location of two keto groups in spireine was revealed by H-NMR and mass spectral analysis of deuterated spireine and tetrahydrospireine. When spireine was heated with selenium at 340°, a compound with molecular formula C20H27NO2 was obtained. Structure 182 was proposed for this compound on the basis of spectral data. Since the C-19 imine bond is usually unstable and cannot be isolated in that form, we suggest that the imine bond is present at C-20 rather than at C-19 in the selenium degradation product (C2oH27N02). Thus, structure 183 should be considered for the latter. Each of the structures considered for spireine has unusual features. The exocyclic double bond in 181 bears some resemblance to lycoctamone (184), a rearrangement product of lycoctonine. 

The genus Consolida, Aconitum, and Delphinium (Ranunculaceae) are well-known to be rich in diterpene alkaloids, which possess a diverse range of biological activities. These plants have also been the cause of poisonings, which primarily occur in cattle as well as human beings, due to toxicity of their alkaloids. In one of our recent studies, five diterpenoid-derivative alkaloids, lycoctonine (9), 18-O-methyllycoctonine (10), delcosine (11), 14-acetyldelcosine (12), and 14-acetylbrowniine (13) (as shown in Fig. 3) were screened for their antibacterial, antifungal, and antiviral activities [39]. 

Even though much is already known about the toxicity of diterpene alkaloids that contribute to the toxicity of Consolida, Delphinium, and Aconitium species, no antiviral study has been so far reported on this type of alkaloids. Therefore, no SAR studies have been encountered by us on the antiviral or antimicrobial activities of these alkaloids. However, a quantitative SAR analysis performed on a number of diterpene alkaloids isolated from an Aconitum sp. indicated that biological activity of these alkaloids may be related to their toxicity rather than to a specific pharmacological action [40]. In a current study on 43 norditerpenoid alkaloids from Consolida, Delphinium, and Aconitum species against several tumor cell lines, lycoctonine and browniine were... 

Briefly, our report was the first on antiviral, antibacterial, and antifungal activities of lycoctonine, 18-O-methyllycoctonine, delcosine, 14-acetyl-delcosine, and 14-acetylbrowniine. Furthermore, our data also suggest that all of the diterpene alkaloids are worthy of being evaluated for their antimicrobial and antiviral activities for future-promising results. 

The numbering systems used for the aconitine, lycoctonine, atisine, and veat-chine skeletons are indicated in structures (A), (B), (C), and (D), respectively. 

B) Lycoctonine skeleton R1 = OR2 (C) Atisine skeleton (D) Veatchine skeleton... 

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