Evodia Alkaloids

Yamazaki, M., and A. Ikuta Biosynthesis of Evodia Alkaloids. Tetrahedron Lett. 1966, 3221. 

Yamazaki, M., A. Ikuta, T. Mori, and T. Kawana Biosynthesis of Evodia Alkaloids. II. The Participation of Ci-Unit to the Formation of Indoloquinazoline Alkaloids. Tetrahedron Lett. 1967, 3317. 

There are several alkaloids in the structure of which are both quinazoline and indole nuclei. Evodiamine (1001 R = H) and rutaecarpine (1002) were both isolated from the seeds of Evodia rutaecarpa about 1916 and synthesized in 1927. They were found subsequently to occur also in Xanthoxylum rhetsa, which in addition yielded rhetsinine (1001 R = OH) (59T(7)257). The plant Hortia arborea afforded two more related alkaloids, hor-tiacine and hortiamine, each characterized by a methoxy group in the benzene ring of the indole portion (60JA5187). 

Several species of Evodia have been stated to contain berberine, but recent workers have failed to confirm this observation. In the Chinese drug, Wou-chou-yu, which is the dried fruit of E. rutcecarpa Benth. and Hook., Asahina and co-workers found two alkaloids, evodiamine and rutascarpine, to which Chen and Chen added a third, wuchuyine, Ci3Hi302N, m.p. 237-5°, [a] f — 60-8°. According to Mayeda, E. 

Evodiamine, the alkaloid from the Chinese drug plant Evodia rutaecarpa Benth. and Hook., has also been called rhetsine and its oxidation product rhetsinine, which is also found in nature, was shown to be the diamide (53). Recently a hypotensive red alkaloid isolated from the Brazilian plant Hortia arborea Engl, was given the name hortiamine. Degradation and synthetic studies have shown it to possess the structure (55). It was found together with another... 

Rutaecarpine (46) is the major alkaloid found in Evodia rutaecarpa (Juss.) Benth., and activities relevant to AD have been identified with the extract and with rutaecarpine. Dehydroevodiamine (47), another alkaloid from the same species, inhibited AChE in vitro, and reversed scopolamine-induced memory impairment in rats and increased cerebral blood flow in vivo in cats, a property which would supplement its usefulness in AD. The structures of (46) and (47) and tacrine (28) have been used as templates for the development of a series of synthetic compounds which have been evaluated for their antiChE activity. These were found to be inhibitory against both AChE and BuChE with A -(2-phenylethyl)-A -[(12Z)-7,8,9,10-tetrahydroazepino [2,l- ]quinazolin-12(6//)-ylidene] amine (48) showing higher affinity for BuChE. 

There is evidence in literature that alkaloid biology is connected with regulation, stimulation and induction functions. Tsai et al. proved that caffeine levels in the blood, brain and bile of rats decreased when given a treatment of rutaecarpine, an alkaloid from Evodia rutaecarpa (Figure 78). It is known that caffeine has been found to enter the brain by both simple diffusion and saturable carrier-mediated transport . The hepatobiliary excretion of caffeine has also been reported in humans rabbits and rats. ... 

Figure 78. Rutaecarpine, an alkaloid from Evodia rutaecarpa.

H. S. and Kim, Y. K. 2002. Quinolone alkaloids, diacylglycerol acyltransferase inhibitors from the fruits of Evodia rutaecarpa. Planta Medica, 68 1131-1133. 

Ueng, Y. E., Wang, J. J., Lin, L. C., Park, S. S. and Chen, C. F. 2001. Induction of cytochrome P450-dependent monooxygenase in mouse liver and kidney by rutaecarpine, an alkaloid of the herbal drug Evodia rutaecarpa. Life Sciences, 70 207-217. 

Evodia rutaecarpa (Juss.) Berth Wu Zhu Yu (Evodia) (fruit) Alkyl methyl quinolone alkaloids, evodiamine, limonin, evocarpine, rutaecarpine, N-methyl anthranilic acid, evodol, hydroxyevodiamine, N-methylanthranflamide, N,N-dimethyl-5 -methoxytryptamine, dehydroevodiamine.32,33,237 Antiemetic, analgesic, lower blood pressure, antibacterial. 

These alkaloids occur in the genera Evodia, Hortia, and Zanthoxylum, all members of the Rutaceae, and are restricted to only a few species. Most of the other species in these genera that have been examined yield furoquinoline and acridine alkaloids. Table I is a record of the occurrences, along with empirical formulas and melting points, of the quinazolinocarboline alkaloids. They are all optically inactive except evodiamine, [a]i> +352° (acetone), which is easily racemized. Wuchuyine, C10H13O2N, mp 237°, [a]D — 18°, occurring in E. rutaecarpa (1), evidently... 

Fig. 13.1 Alkaloids extracted from the Chinese traditional medicinal herbs Coptidis rhizoma and Evodiae fructus and analyzed using C18 reversed phase HPLC-ESI-MS.

C]Tryptophan gave inactive alkaloids but tritiated 2,4-dihydroxy-quinoline (34) and its N-methyl derivative were incorporated into (47) (0.009 % and 0.020% respectively) an early route had suggested the derivation of what was essentially (34) from tryptophan. Radioisotope dilution showed the presence of both these quinoline precursors together with iV-acetyl- and N-methyl-anthranilic acid in A. baueri. A satisfactory incorporation of N-methylanthranilic acid into (47) was found in Evodia xanthoxyloides, and this, together with its natural occurrence, indicates that early methylation may be important in the biosynthesis of acridone alkaloids. 

Dreyer (172) reinvestigated the alkaloids of Evodia xanthoxyloides F. Muell and isolated a new furoquinoline alkaloid, C17H17NO4, with a UV... 

Dreyer (172) obtained another new alkaloid, the epoxide 174, from Evodia xanthoxyloides its structure was determined by NMR spectroscopy and by acid hydrolysis to evoxine (175). The isolation of epoxides 167 and 174 from E. xanthoxyloides and the failure to detect evoxine, previously obtained from this species, are of considerable interest because of the fact that acid was employed in the earlier isolation work, it was suggested that evoxine may be an artifact derived from the corresponding epoxide. 

Five acridone alkaloids were obtained previously from the bark of Teclea boiviniana cf. Vol. 6, p. 108) a recent investigation showed that the constituents of the leaves are similar, and resulted in the isolation of arborinine (37 R = H), tecleanthine (38 R = H, R = OMe), evoxanthine (38 R = R = H), 6-methoxytecleanthine (38 R = R = OMe), and 1,3,4-trimethoxy-iV-methyl-acridone (39 R = Me, R = OMe). The latter compound has not been obtained previously from a natural source. The n.m.r. and mass spectra indicated that the new alkaloid was a trimethoxy-iV-methylacridone and that ring A was unsubstituted. The three possible acridones had been synthesized earlier, and from melting-point data the alkaloid appeared to be the 1,3,4-trimethoxy-derivative this was confirmed by synthesis using a modification of the published procedures. 1,2,3-Trimethoxy-iV-methylacridone (37 R = Me), previously isolated from Evodia alata, has now been obtained from Melicope leratii. The known alkaloids melicopidine (40 R = Me, R = OMe) and xanthovedine (40 R = R = H) were also shown to be constituents of M. leratii. Arborinine (37 R = H) has been obtained from Vepris pilosa and from Ruta chalapensis. Other known acridone alkaloids isolated from a new source include the l-hydroxy-3-methoxy-deriva-tive (39 R = R = H) and its methyl ether (39 R = Me, R = H), from Vepris pilosa. ... 

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