Narceine alkaloids

Phthalideisoquinolines.—The new alkaloid narceine imide (162) has been obtained from extracts of Papaver somniferum L. (Papaveraceae). Gnoscopine [( )-narcotine] has been synthesized by a classical route. 

Estimation of Other Alkaloids in Opium. Of the other alkaloids the most important is codeine, and processes for its estimation in opium have been described by Cespari, Andrews,and Annett and co-workers methods for its assay in admixture with other drugs in tablets and other products are also available. The estimation of papaverine has been described by Issekutz,i and of narcotine by Snesarov. As to methods for the separation and estimation of two or more of these subsidiary alkaloids, codeine and narcotine have been dealt with by van der Widen,narcotine and papaverine by Annett and Bose, ( and the bromination of codeine and narceine has been studied by Vaisberg et al. with a view to estimation by this means. 

The first scheme for the separation of the six chief alkaloids of opium, VIZ., morphine, codeine, thebaine, papaverine, narcotine and narceine, is probably that of Plugge. Much later Kljatschkina investigated for each of these six bases the properties by means of which isolation and estimation could probably be effected and, on the basis of the results, devised a plan for such analyses. More recently Anneler has published a detailed account of a scheme with the same objective. l Attention had already been given to complex, systematic analyses of this kind, in connection with examination of the mixtures of opium alkaloids, which have long been in use in medicine in these at first only morphine and other alkaloids were determined, but in the more recent schemes provision is made for the estimation of each alkaloid. ... 

The processes used in the manufacture of morphine are believed to be still based on that described by the Scottish chemist Gregory,in 1833, with improvements devised by Anderson. A description has been published by Schwyzer, who also deals with the manufactme of codeine, narcotine, cotarnine, and the commercially important morphine derivatives, diamorphine (diacetylmorphine), and ethylmorphine (morphine ethyl ether). More recently Barbier has given an account of processes, based on long experience in the preparation of alkaloids from opium. Kanewskaja has described a process for morphine, narcotine, codeine, thebaine and papaverine, and the same bases are dealt with by Chemnitius, with the addition of narceine, by Busse and Busse, and by Dott. It is of interest to note that a number of processes for the extraction and separation of opium alkaloids have been protected by patent in Soviet Russia. ... 

Narceine, C23H2,OjN. aHjO. This alkaloid was obtained by Pelhtier in 1832, and was subsequently eharaeterised by Couerbe and by Anderson, The latter assigned to it the formula, C23H29O9N, whieh was aeeepted until Freund observed that the base erystallised with 3 mols of water, of whieh only two are lost at 100°. Anderson s base therefore was C23H2,OgN. HjO. 

Oxynarcotine, CjjHjaOgN. This alkaloid was separated by Mayer, and later by Beckett and Wright, from crude narceine. It crystallises from hot alcohol in small needles. Its close relationship to narcotine is shown by the formation of cotarnine, C12H15O4N (p. 201), and hemipinic acid when it is oxidised by ferric chloride narcotine under these circumstances furnishing cotarnine and opianic acid. Rabe and McMillan regard oxynarcotine and nomarceine as identical. 

This procedure yielded a colorless background, on which the colors of the alkaloid zones became pale brown (narceine), blue (morphine) or violet (codeine, papaverine, narcotine) (Fig. 2B). 

From a historical standpoint, the first secoisoquinoline alkaloid was narceine, isolated from opium by Pelletier as early as 1832 (/). Up to 1986, over 70 secoisoquinoline alkaloids had been discovered. Most of them were found... 

The first secoisoquinoline alkaloid discovered was the secophthalideisoquinoline, narceine (106), isolated from opium by J. Pelletier in 1832 (7). Up til now 19 natural bases belonging to this group have been isolated, and 6 others have been synthesized. Secophthalideisoquinoline alkaloids have been described in several reviews papers by Shamma et al. 2,4,5), by Santavy (7), and most recently, in 1985, by MacLean (5). 

In this chapter the proposed (5) division of secophthalideisoquinolines into the four subgroups and the nomenclature have been preserved. Since the publication of the most recent review (5), information about the synthesis of the missing ( )-narceine enol lactone (102) (87), the isolation of ( )-fumaramine (112) from Fumaria vailanti (88), and the discovery of a new seco alkaloid, coryrutine (118), from Corydalis rutifolia (89) has appeared. In the former plant fumaramine (111) (55) and in the latter N-methylhydrasteine... 

The secophthalideisoquinoline enol lactones may exist as Z or geometric isomers. Three pairs of such isomers are known aobamidine (96) (Z) and adlumidiceine enol lactone (97) ( ), /V-methylhydrastine (98) (Z) and (E)-N-methylhydrastine (99) ( ), (Z)-narceine enol lactone (101) and ( )-narceine enol lactone (102). Three of these enol lactones (99, 101, 102) are synthetic products. Lists of these alkaloids, the plant species in which they occur, as well as their spectral data and other references are provided in the review papers (4,5,8). Narceine enol lactones (101 and 102) are described in Refs. 87 and 90. 

The enol lactones were synthesized by Hofmann degradation of metho salts of classic phthalideisoquinoline alkaloids. The biogenetically relevant transformations were highly stereospecific. In this way aobamidine (96) was obtained from the methiodide of (erythro) bicuculline (88) (2), and ad-lumidiceine enol lactone (97) was produced from both (threo) isomeric adlumidiceine (89) and capnoidine (90) methiodides (14,15,91-93). (Z)- (98) and ( )-N-methylhydrastine (99) were obtained from / - (91, erythro) and a-N-methylhydrastinium (92, threo) iodides (5,87,91,96-98), respectively, as were (Z)- (101) and (JE)-narceine enol lactones (102) synthesized from a- (94, erythro) and /J-narcotine (95, threo) quaternary N-metho salts (87,90), respectively. In a similar process /J-hydrastine (91) JV-oxide heated in chloroform yielded enol lactone 124 of Z configuration (99) however, a-narcotine (94) N-oxide was transformed to benzoxazocine 125 (99). ... 

A great number of transformations has been performed on narceine imide (116) by Czech researchers. Oxidation with potassium permanganate in acetone or with nitric acid caused the cleavage of the alkaloid, giving rise to hemipinic imide (127). A similar result was noted by Rdnsch (129,130) during Lemieux-Johnson oxidation of ene lactam 152 (129,130) in this reaction the basic component (156) was isolated as well. The use of hydrogen peroxide in acetone converted 116 to (Z)-narceine imide N-oxide, which under the action of acetic anhydride underwent N-dealkylation (135). 

More than 30 alkaloids have been identified in opium (Robbers et al. 1996). The most relevant are morphine (4-21%), codeine (0.8-2.5%), noscapine (4-8%), papaverine (0.5-2.5%), and thebaine (0.5-2%) (figure 8.4). Other opium alkaloids include narceine, protopine, laudanine, codamine, cytopine, lanthopine, and meconidine. Numerous other opioids have been synthesized from opium alkaloids. Among them is heroin, or diacetylmorphine. 

Soaking plants parts in alcohol (ethanol) creates a tincture. In this process, pharmacologically active constituents of the plant are extracted by the alcohol. Tinctures do not contain the complete spectrum of substances that exist in the plant or crude drug, only those that are soluble in alcohol. In the case of opium tincture, these ingredients are alkaloids (i.e., basic substances of plant origin) including morphine, codeine, narcotine = noscapine, papaverine, narceine, and others. 

Alkaloids such as boldine, codeine, narceine and morphine are active factors in their receptors. Boldine has morphine-like properties and is active on opioid receptors. It may be used to treat stomach disorders and as metabolic stimulant. As it is similar to morphine, boldine can also be considered in the possible development of treatments for narcotic dependence. Codeine also binds to opiate receptors, and specifically functions to reduce bronchial secretions. Codeine can also be used as a cough suppressant when acting on the centre of the medulla oblongata and as a sedative agent. 

Morphine and narceine are active on / -opiate and K-receptors. They are also known as analgesic agents. These alkaloids may be used as pain relievers. Narceine is also known to be used in the treatment of a cough. 

Alkaloids such as boldine, codeine, narceine and morphine are also important in clinical practice. Boldosal and Oxyboldine are good examples of boldine-based drugs with morphine-like properties. 

Therefore the influence of temperature and humidity on the robustness will be investigated. The maximum number of alkaloids to be separated in the paper of Coenegracht et al [3] was six in opium, and the separation of seven alkaloids in this paper is a severe test of the four solvent systems suitability for the separation of alkaloids. The alkaloids are strychnine, quinine, narceine, heroin, noscapine, caffeine and papaverine. 

A robust TLC separation of the seven alkaloids (strychnine, quinine, heroin, noscapine, caffeine, papaverine and narceine) is difficult to obtain. The solutes used have different properties and can therefore not be separated trustworthy for all possible values of relative humidity and temperature. 

Phthalide isoquinoline alkaloids Hydrastine. narceine, narcotine... 

There are at least 25 alkaloids of opium belonging to different chemical classes morphine (about 10 % of opium), noscapine or narcotine (about 5 %), papaverine (1 %), codeine (0.4 %), tebaine (0.4 %), narceine (0.2 %), but not all of these possess psychotropic effects. The illicit opiates may be natural molecules, such as morphine and codeine, and semisynthetic, such as heroin. Methadone and meperidine represent a group of totally synthetic molecules with opiate psychotropic effects. 

In 1803 the German pharmacist Seturner achieved the isolation of morphine as one of the active ingredients of opium. He named the compound after Morpheus, Ovid s god of dreams, the son of sleep. Among the other alkaloids of opium are codeine, isolated in 1832, thebaine, narceine, narcotine, and papaverine. From the isolation of pure morphine to the elucidation of its structure by first Gulland and Robinson(1,2) and later Schopf(3) took another 120 years. A total synthesis by Gates and Tschudi(4,5) confirmed the structure in the early 1950s. 

For the identification of a number of opium alkaloids (morphine, codeine, thebaine, noscapine, papaverine, cryptopine, narceine) and heroin, 3-0-acetylmorphine, 6-0-acetylmorphine and acetyl codeine, Viala et al. 7 made use of three gas chromatographic columns of different polarities (SE-30 3 %, OV-1 2 % and OV-1 2 % plus Igepal 0.2 %).They obtained reliable separation and identification in this way, which was based on the difference in the retention times in the three columns. 

Fig. 7.7. Separation of some opium alkaloids Column Zorbax NH (250x4.6 mm ID), mobile phase acetonitrile - 07025 M potassium dihydrogen phosphate (3 1), flow rate 2.0 ml/min, detection UV 286 nm. Peaks 1, papaverine 2, thebaine 3, narceine 4, codeine 5, morphine 6, tyrosine (internal standard).

The aqueous extract of opium is treated with sodium acetate and the precipitated narcotine and papaverine collected, the filtrate concentrated to small bulk with sodium acetate when narceine is precipitated and removed, thebaine being finally isolated from the filtrate as its sparingly soluble salicylate. In this way 90 per cent, of the alkaloid can be extracted [12-13]. 

The alkaloids of opium have not the same action. In soporific action, beginning with the most powerful, they rank thus Narceine, morphine, codeine in tetanizing action thebume. papaverine, narcotine, codeine, morphine in toxic action thebaine. codeine, papaverine, narceine, morphine, narcotine. 

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