Alkaloids cephaeline

The structure of tubulosine (83) was derived principally from its mass spectrum which is similar to that of the Ipecacuanha alkaloid cephaeline and is characterised by main peaks at m/e 288, 274, 201, and 187," cf. (83). Oxidation of (83) gives... 

The phenolic alkaloids cephaeline and psychotrine couple with p-nitrophenyldiazonium salts in alkaline solution to give purple dyestuffs (67), the absorption spectra of which are characteristic (68). Emetamine, because of its ditertiary nature does not form such a compound, contrary to the prior opinion of Palkin and Wales (68, 69). 

Maugh TH (1984) Semisynthetic enzymes are new catalysts. Science 223 154-156 Nagakura N, Hofle G, Zenk MH (1978) Desacetylipecoside the key intermediate in the biosynthesis of the alkaloids cephaeline and emetine. J Chem Soc Chem Commun 896-898 Prakash O, Bhakuni DS, KapU RS (1979) Biosynthesis of coclaurine. J Chem Soc Perkin Trans I 1515-1518... 

The roots of Cephcelis Ipecacuanha (Brot) A. Rich constitute the Brazilian ipecacuanha of commerce and also that cultivated in the Federated Malay States, Bengal and Burma. Carthagena ipecacuanha is derived from Cephcelis acuminata Karsten collected in Colombia. Emetine, the principal alkaloid of this drug, was first obtained by Pelletier and Magendie in 1817, but was first prepared in a pure state by Paul and Cownley, who separated from commercial emetine the phenolic base, cephaeline, and later obtained a third alkaloid, psychotrine. To these Pyman added emetamine and 0-methylpsychotrine. 

Processes for the extraction of the total alkaloids and isolation of the-individual bases will be found in the papers cited above. Cephaeline is too toxic for medical use and is usually converted into emetine by methyla-tion of the phenolic hydroxyl group, and processes have been patented for this purpose, beginning with that of Wellcome, Carr and Pyman in 1913. ... 

Methylation of the Alkaloids. When cephaeline is treated with methyl sulphate or sodium methyl sulphate under various condition, there is formed in addition to emetine (which was first shown to be the methyl ether of cephaeline and partially synthesised in this way by Carr and Pyman in 1913), more or less N-mcthylcephaeline (wedge-shaped plates, m.p. 194 5°), and N-methylemetine. The latter is also obtained by direct methylation of emetine it is amorphous, [a]n — 52-6° (CHCI3), but yields a hydrobromide, C33H42O4N2.2HBr. 3H2O, m.p. 210-30°, [ajp + 5-6° (H2O). 

Note Under the conditions employed emetine and cephaeline were not well separated but there was good resolution of the subsidiary alkaloids of the ipecacuanha tincture (Fig. 1). The separation and quantitative determination of the main alkaloids (Fig. 2) can be carried out under the following conditions Ascending, one-dimensional development in a trough chamber with chamber saturation layer HPTLC plates Silica gel 60 (Merck) mobile phase dichloromethane — methanol — ammonia solution (25%) (34+6+1) migration distance 6 cm running time 13 min h/ f cephaeline 65-70 emetine 75-80. 

From dopamine, the pathway of tetrahydroisoquinoline alkaloids, such as emetine and cephaeline (Figure 37), also begins. Dopamine and secologanin undergo a Mannich-like to produce A-deacetylisoipecoside and ipecoside, and after hydrolysis and transformation, this is converted to emetine and cephaeline. 

These alkaloids have a phenyl or phenylpropyl nucleus. The group includes simple phenyl amine (tyramine, hordenine), catecholamine (dopamine, noradrenaline, adrenaline), simple tetrahydroisoquinoline (mescaline, anhalamine, anhalonine, anhalonidine), benzylisoquinoline (e.g., papaverine), phthalideiso-quinoline (e.g., noscapine), phenethylisoquinoline (autumnaline, floramultine and kreysigine), tetrahydroisoquinoline (emehne and cephaeline) and terpenoid tetrahydroisoquinoline (secologanin and ipecoside) alkaloids. 

The antidiarrhoeal drug ipecac, which was introduced into Europe from Brazil in 1658, contains the amoebicidal alkaloids emetine (12) and cephaeline. Emetine remained the major remedy for amoebic dysentery and amoebic hepatitis for many years. Cephaeline is less active and more toxic. ( j-2-Dehydroemetine, which is made by synthesis, is equiactive with (—)-emetine and less toxic, but other chemical modification has not yielded better amoebicides. From investigations of synthetic routes to the benzoquinolizine moiety the tranquilizer tetrabenazine (13a) was discovered. The very similar compound benzquinamide (13b) is also a tranquilizer and antiemetic. 

Fig.4.57. Separation of some DNS-alkaloids by TLC. 1 = tri-DNS-adrenaline 2 = mono-DNS-ephedrine 3 = di-DNS-cephaeline 4 = mono-DNS-emetine 5 mono-DNS-morphine 6 = DNS-side product.

Fig.4.58. Separation of DNS-alkaloids by HPLC (see text for details). Peaks 1 = emetine 2 = cephaeline 3 = ephedrine.

Ipecac contains 2-2.5% of alkaloids, the principal ones being emetine and cephaeline (Figure 6.67). Typically, in C. ipecacuanha the emetine to cephaeline ratio might be about 2 1, whereas in C. acuminata the ratio ranges from about 1 2 to 1 1. Minor alkaloids characterized include psychotrine and O-methylpsychotrine (Figure 6.68), which are dehydro variants of cephaeline and emetine respectively. 

Ipecac, the root of a Brazilian plant, contains several alkaloids of which two, emetine and cephaeline, produce local irritation and nausea and emesis, by central and local action, without danger of side effects. 

Ipecac is the root of Cephaetis ipecacuanha, or of C. acuminata, a perennial shrub growing in Brazil and other South American states (Figure 44.1). It contains three alkaloids — emetin, cephaelin, and psychotrin. The dose of the powdered drug as an expectorant is from 1/2 to 2 grain (0.03 to 0.13 g) as an emetic, 15 to 30 grain (1.0 to 2.0 g) (Table 44.1). 

Emetine was first described in 1817 by Pelletier, the discoverer of quinine. However, Pelletier was actually dealing with a mixture of the alkaloids of ipecac, that is, emetine, cephaeline, and psychotrine (see Grollman, 1962). 

The efficacy of ipecac in amebic infections depends upon its content of alkaloids, the principal ones being emetine and cephaeline. Both are amebicidal, but emetine is much more active. Cephaeline is more toxic than emetine, except for the heart, and causes more nausea and vomiting. Emetine constitutes more than one half of the total alkaloidal content of ipecac. 

Cephaeline (2), psychotrine (6), ankorine (13), venoterpine (25), and ( )-anabasine (28) have also been found in some other species of Alangium (18,19) and the alkaloid, C28H35N303 [mp200°C [ ] —40° (pyridine)], in the bark of A. vitiense (20). It is interesting to note that emetine (1) has been isolated from Hedera helix L. (family Araliaceae) (21,22). 

Emetine in A Emetine in B Cephaeline in A Cephaeline in B Psychotrine in A Alkaloids in A Ipecac alkaloids in B Emetine Emetine in A Emetine in B Emetine in C Cephaeline Cephaeline in A Cephaeline in B Emetine Emetine Emetine in B Ipecac alkaloids in B Emetine Emetine in A Emetine in B Cephaeline Emetine Emetine in A Emetine in B Cephaeline in A Emetine Emetine in B Emetine in C Cephaeline... 

The close biogenetic relationship of the ipecac and monoterpenoid indole alkaloids has already been reviewed in several places (3,5,117,287). In the case of the ipecac alkaloids, tracer experiments (288) have shown that labeled geraniol (146) and loganin (148) are incorporated by Cephaelis ipecacuanha into radioactive cephaeline (149) and ipecoside (150). Thus, the C9-C,0 units of the ipecac alkaloid and ipecoside, represented by thickened lines in formulas 149 and 150, are of monoterpenoid origin from geraniol (145), and loganin (147) acts as a precursor for both alkaloids. The incorporation of glycine into the C9 unit of cephaeline (2) in Cephaelis plants has also been reported (289). 

The root of Cephaeiis ipecacuanha, also known as Psychotria ipecacuanha, is the source of ipecacuanha, which contains the emetic alkaloids emetine and cephaeline. Ipecacuanha is covered in a separate monograph. 

The root of the ipecac is commonly used as an expectorant in the treatment of bronchitis, croup, asthma amoebacide and whooping cough, as an emetic in cases of poisoning, and an amoebacide in amoebic dysentery. It has appeared in the Japanese Pharmacopoeia (2001) as ipecac, powdered ipecac and ipecac S)nxip [6]. The ipecac is rich in isoquinoline alkaloids such as emetine, cephaeline, psychotrine. 

The supply of ipecac has fluctuated for many years because it is collected mainly from wild habitat. The Rio variant is now becoming difficult to obtain commercially, and the high price favors cultivation, but only modest success has been achieved from the efforts made to grow the plant in Malaya and India. The ipecac used in Japan is imported from abroad at a rate of 100%, consequently giving variation of alkaloid value and ratio of emetine and cephaeline [10]. 

Ipecac contains many isoquinoline alkaloids as mentioned above and the value of the regenerated plants through tissue culture greatly depends on their phytochemical similarities to the crude drug. Therefore, improved HPLC system for the analysis of the isoquinoline alkaloids, not only emetine and cephaeline but also minor constituents, was investigated [19]. 

Although the ion pair HPLC for emetine and cephaeline using sodium 1 -heptanesulfonate as a counter ion and methanol for a mobile phase was previously reported [20], compounds other than emetine and cephaeline in the leaf extract of ipecac were not well-separated. Therefore, a different type of ODS column, TSK gel ODS-120A column (4.6 mm i.d. x 250 mm, TOSOH Co., Japan) was selected because it previously provided a good separation of the tropane alkaloids [21-23] and the Papaver alkaloids [24]. 

Authentic alkaloids, emetine, cephaeline and protoemetine, were dissolved in an appropriate volume of methanol and injected onto a TSK gel ODS-120A column, the elution parameters such as the type of counter ion. Fig. (7), the pH of the mobile phase. Fig. (8), and column temperature. Fig. (9), were examined to find an optimal condition employing a flow-rate of 1.0 ml/min and UV detection at 285 nm. 

The alkaloid contents of the lY-plants are shown in Fig. (16). The leaves contained lower amount of alkaloids than roots and rootlets. The alkaloid contents in the roots of 1 Y-plants increased from June to December in Tanegashima, while they decreased in September and October in Tsukuba. The roots of 1 Y-plants in a greenhouse demonstrated relatively stable alkaloid contents. The maximum alkaloid contents in the roots were obtained in December both in Tsukuba (2.4% dry weight cephaeline, 1.0% dry weight emetine) and Tanegashima (3.2% dry weight cephaeline, 1.8% dry weight emetine). 

The alkaloid contents of adventitious shoots in liquid medium were quantified by HPLC, Fig. (20). They produced alkaloids, especially cephaeline (0.4 - 0.6% dry weight), and there was no obvious difference in alkaloid contents among different concentrations of BA. This result indicates that ipecac shoots, formed on intemodal segments, have the capabilities of alkaloid biosynthesis. 

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