Alkaloids emetine

More recently Openshaw and Whittaker3 in a synthesis of emetine alkaloids needed to effect condensation of an amine with a low-energy ester and in the particular case studied found that use of hydroxy pyridine raised the yield from 2% to 87%. Twelve other mono- or polyhydroxylated heterocyclics were examined, but 2-hydroxypyridine was clearly superior. 

The emetine alkaloids and their derivatives from Uragoga species are the object of renewed medical interest. Stahl [228] recommends double development with chloroform-methanol (85 + 15) on silica gel G, using chamber saturation, for separating these alkaloids. He found the most sensitive detection to be spraying with about 10 ml of a 0.5% solution of iodine in chloroform, followed by heating 15 min at 60° C ( ) the alkaloids then fiuoresce intensely yellow or blue in UV light (365 nm). 

There is a relatively large number of alkaloids which maybe considered as simple phenethyl amine [64-04-0] (59, R = H), CgH N, or tyramine [51-67-2] (59, R = OH), CgH NO, derivatives. These iaclude mescaline (61) from the small wooly peyotyl cactus l ophophora mlliamsii (L emaire) Coult. anhalamine (62) and lophocerine (63) from other Cactaceae, and the important antamebic alkaloids (—)-protoemetiae (64), (—)-ipecoside (65), and (—)-emetine (66) from the South American straggling bush Cephaelis ipecacuanha (Brotero) Rich. AH of these bases appear to be derived from tyrosiae (25,... 

Ipecac is prepared from the dried roots and rhizomes of Cephaelis ipecacuanha (Brot.) A. Rich, and contains the alkaloids emetine [483-18-1] (17) and cephaeJine [483-17-0] (18) in a ratio between 2 1 and 4 1. It has been used extensively in cough preparations and is beheved to act by gastric reflex stimulation. Toxic effects include vomiting, irritation of the gastrointestinal tract, and cardiac arrhythmias (19). Ipecac symp is available over-the-counter in the United States only in 30-mL containers for use as an emetic in treating poisonings. 

Emetine andcephaeline, the two major alkaloids of ipecacuanha, begin to fluoresce after treatment with iodine vapor [254], The molecular iodine, which acts as a quencher, must be removed by heating in the drying cupboard or on a hotplate... 

There are now known a eonsiderable number of alkaloids containing two distinct woquinoline nuclei, such as emetine and its congeners (p. 394), and in the morphine sub-group, -morphine, dithebainone (p. 255), disinomenine and its pseudo-isomeride (p. 268). The most important collection of such alkaloids is the bisbenzylwoquinoline or biscoclaurine section of which the following two alkaloids, berbamine and oxyacanthine, are examples, but which is typically developed in the Menispermaceas. 

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. ... 

A method for the estimation of the total alkaloids and of non-phenolic alkaloids (emetine fraction) is given in the British Pharmacopoeia, 1932, Addendum VI, which requires the drug to contain not less than 2 per cent, of alkaloids, of which at least 55 per cent, must be non-phenolic bases, calculated as emetine. The British Pharmacopoeia also gives an assay process for emetine in emetine bismuth iodide, the form in which the drug is chiefly used in medicine it is required to contain not less than 25 and not more than 28 per cent, of emetine. In the United States Pharmacopoeia, XIII, both Cephcelis Ipecacuanha and C. acuminata are recognised and must contain not less than 2 per cent, of ether-soluble alkaloids. 

Owing to the frequency with which the botanical attribution of ipecacuanha has been changed, and to the considerable number of substitutes which have from time to time appeared, it is difficult to summarise briefly the botanical distribution of the ipecacuanha alkaloids, and readers interested in this subject may be referred to Staub for information and references. Freise states that emetine and the allied bases are to be found in certain Rubiaceous spp. not usually regarded as sources of these alkaloids, and Orazi has stated that the roots of Bourreria... 

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). 

It has been shown by various workers 3 that the action of alkaloids on protozoa is influenced in a marked degree by the pH of the medium in which the action is exerted, and at a pH of 6-2 to 6-3 aK-tetra-n-amyl-diamino-n-decane proved to be 3 to 5 times as active as emetine, and even in presence of blood at least as active. In view of these promising results of in vitro tests the synthetic product was tried clinically, but proved not to be sufficiently active to be of practical value. This work is being continued and extended by a team of workers led by Goodwin and Sharp, who have published two papers dealing (1) with amines which can be regarded, like Pyman s type A, as diamines derivable from the accepted emetine formula and (2) variants on the bis(diamylamino) decane referred to above. 

Kurchi bark is principally used in India as a remedy for amoebic dysentery, and in recent years there has been a revival of medical interest in the drug in this eonneetion. It is generally used in the form of a bark extract but, in imitation of emetine bismuth iodide, kurchi bismuth iodide, consisting of the bismuth iodides of the mixed alkaloids of the bark, has also been used. On the pharmaceutical side Datta and Bal have studied the pharmacognosy of the bark and a method of alkaloidal assay has been devised by Schroff and Dhir, who have also described a process for the preparation of kurchi bismuth iodide, a product for which they, and also Mukherjee and Dutta, have provided methods of assay. 

Comparatively few alterations have been made since 1989 in the structures accepted for well-known alkaloids. A slight but important change has been adopted in the formula of strychnine and contributions to the chemistry of that alkaloid and its associates are still being made, though the formula seems now so well established that Woodward has recently suggested and discussed a scheme for the biogenesis of strychnine on which Robinson has commented favourably. Robinson has also proposed a scheme for the biogenesis of emetine. This involves a modification in the formula of that alkaloid, which is supported by Dewar s interpretation of the results of recent chemical work on emetine by Karrer et al., by Spath and by Pailer. ... 

The most widely used emetic is syrup of ipecac, containing the alkaloids, emetine and cq haeline. Emetine induces vomiting by activation of sensory neurons in the vagus and sympathetic nerves to the stomach and centrally in the medulla, possibly at the CTZ. The release of serotonin and SP may be involved as 5-HT3 and NKi receptor antagonists prevent emesis induced... 

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. 

Note It is possible to differentiate amino acids by color on the basis of the markedly different shades produced [2, 3]. Proline and hydroxyproline, that only react weakly with ninhydrin, also yield pink-red colored derivatives [2]. Ergot alkaloids and LSD are detected by spraying with 10% hydrochloric add and then heating to 110°C for 20 min after they have been treated with the reagent [9]. Ergot alkaloids and LSD yield red to purple zones when treated in this manner other alkaloids, e.g. reserpine, emetine, quinine, strychnine, pilocarpine, atropine, scopolamine, cocaine and opium alkaloids, do not give a reaction [9]. 

Zhou YD et al (2005) Terpenoid tetrahydroisoquinoline alkaloids emetine, king me. and isocephae-line inhibit the activation of hypoxia-inducible factor-1 in breast tumor cells. J Nat Prod 68(6) 947-950... 

Another class of alkaloids recently synthesized by Tietze and coworkers using a three-component domino Knoevenagel/hetero-Diels-Alder reaction included the Ipecacuanha alkaloids such as emetine (2-798) [402], and the Alangium alkaloids such as tubulosine (2-799) [403]. Both types belong to the group of tetrahydroi-soquinoline alkaloids, and are formed in Nature from dopamine and the monoter-... 

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. 

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