Canthin-6-one alkaloids

Several kinds of j8-carboline derivatives have been isolated from fungi since the first isolation of canthin-6-one alkaloids from this toadstool. 

Taylor (5) reviewed some of the canthin-6-one alkaloids such as canthin-6-one (1), 4-methylthiocanthin-6-one (6), 5-methoxycanthin-6-one... 

Thirty-five canthin-6-one alkaloids have been isolated from 36 species... 

Methoxycanthin-6-one (15) has been isolated from the bark of both the stem and root of Charpentiera obovata (Amaranthaceae) (32) and the aerial parts of Drymaria cordata (Caryophyllaceae) (33). This is one of the compounds not found in the families Rutaceae and Simaroubaceae. Its UV and IR spectra proved that it was a canthin-6-one alkaloid, and the H-NMR spectrum confirmed the methoxyl funclion. As natural 15 was identical with an authentic compound synthesized by Nelson and Price (31), structure 15 was determined. 

Methylthiocanthin-6-one (6) is one of the first canthin-6-one alkaloids isolated from the bark (stem, root, branch, and sapling) and wood of Pentaceras australis (31) together with 1 and 7 (5). Readers are referred to Volume 3 (p. 249) of this treatise for its structure (5). 

Both 1-hydroxy-11-methoxy- (24) and 11-hydroxy-1-methoxycanthin-6-one (25) have been isolated from the wood of B. antidysenterica (26, 47). In addition, 24 has been isolated from its root bark (47) and 25 from Soulamea pancheri (28). The UV spectrum of 24 shows a bathochromic shift on addition of alkali, and its mass spectrum shows the molecular ion at mlz 266 (M, 100%). These facts support the supposition that 24 is a canthin-6-one alkaloid which has a hydroxyl and a methoxyl substituent. Since the H-NMR spectrum shows aromatic proton signals, a pair of vicinal protons at H-4 and H-5, a singlet at H-2, and three protons from H-8 through H-10, it is assumed that this compound is either 24 or 25. The H-NMR spectrum of 24 is not the same as that of 25, and irradiation of... 

Over 30 canthin-6-one alkaloids have already been isolated, and their... 

By comparing ring C of 1 with its model compound, pyridine, it is seen that spin-spin coupling constants of the two are very similar (Fig. 2). Both carbonyl carbons at position 6 of 1 and in acrylic acid, which is the model compound of 1, have very large J values for vicinal trans coupling (Fig. 2), and this fact also strongly supports the assignment of carbon atoms in canthin-6-one alkaloids. 

Similarly, Crespi-Perellino et al. (13,15), using cell cultures of A. altissima and providing L-, D-, and D,L-[w(7Av/cz c- C lryptophan as the precursor, carried out tracer experiments and proved the biosynthetic pathway to canthin-6-one alkaloids to be as follows (Scheme 7) tryptophan )8-carboline-l -propionic acid — 4,5-dihydrocanlhin-6-one (29) canthin-6-one (1)—> l-hydroxycanthin-6-one (10) l-methoxycanthin-6-one (11) —> l-methoxycanthin-6-one 3-oxide (12). In the biosynthetic pathway to canthin-6-one alkaloids, oxidation proceeds stepwise. The hydroxyl group at position 1 of canthin-6-one is methylated, and 11 is readily formed this formation is considered to be a transmethylation promoted by a specific enzyme. 

The antiherpes activity of four kinds of canthin-6-one alkaloids was assayed biologically together with 10 /3-carboline derivatives. Among these compounds, 8 and 28 had activity on a level with that of acyclovir, the control. It was noticed, however, that the therapeutic ratio was small 106). 

With the inhibitory activity against cyclic adenosine monophosphate phosphodiesterase as an index, in vitro bioassay of the activity of 21 canthin-6-one alkaloids was carried out. The strongest inhibitory activities were detected with 4, 17, and 27 among the compounds tested. The activities shown by 10, 28, and 34 were the same, twice as strong, and 15 times as strong, respectively, as the activity of papaverine, the control. Acetylation and methylation of the hydroxy derivatives of canthin-6-one decreased activity (108,109). 

Table I is a compilation of plant species which contain the simple indole alkaloid types of Fig. 1. As mentioned earlier, the main requirement for the inclusion of a certain simple indole alkaloid into Table I is that it contain a tryptamine unit as a readily distinguishable feature in its structure. That tryptamine is a precursor in the biosynthesis of many of the b, c, d, and e type simple indole bases is yet to be shown although it is felt that future work will prove the correctness of such a view. Gramine, the simplest indole alkaloid, has been included in the tryptamine classification a because it is biosynthetically related to tryptophan cryptole-pine has been likewise included therein although its structural relationship to tryptophan appears more obscure (Volume VIII, Chapter 1, pp. 4, 19). The calycanthine type does not possess a tryptamine structure but it is included in the simple indole alkaloid b classification since most of its congeners are tryptamine derivatives and since it exhibits a close biogenetic relationship to this latter (chimonanthine) type (Volume VIII, Chapter 16). Type d is represented by the small number of the so-called canthin-6-one alkaloids (Volume VIII, pp. 260-252, 497-498). The most recent variation of the simple indole alkaloids is found in the Anacardiaceae family. Its indoloquinolizidine nucleus suggests inclusion with type d on the basis of structural and biogenetic similarity. Finally, simple indole alkaloid type e is composed of the well-defined evodiamine (rutaecarpine) structural form (Volume VIII, Chapter 4).

The molecular skeleton of infractopicrin resembles that of vincamine, a representative alkaloid which lowers blood pressure, isolated from plants of the genus Catharanthus (Vinca). There is, however, no evidence of a biogenetic relationship of these alkaloids, and the absence of an angular ethyl group in infractopicrin and in the accompanying metabolites suggests rather different biosynthetic pathways in both cases (177). Studies on the canthin-6-one alkaloids of various natural origins were recently reviewed by Ohmoto and Koike in Volume 36 of this treatise (179). 

Only two species of Simaroubaceae plants are known in Japan, namely P. ailanthoides described above, and Ailanthus altissima. The former plant grows wild in Japan, whereas the latter plant is a deciduous ornamental tree native to China that was imported into Japan at the end of the nineteenth century. This tree is known as Tree of Heaven, meaning that this tree grows very fast to be able to touch heaven quickly. Canthin-6-one alkaloids isolated from Simaroubaceae plants were reviewed by Ohmoto and Zasshi [5]. 

Ferreira ME, Rojas AA, Torres OS et al (2002) Leishmanicidal activity of two canthin-6-one alkaloids, two major constituents of Zanthoxylum chiloperone var. angustifolium. J Ethnopharmacol 80 199-202... 

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