Cryptopine alkaloids

Alles GA, Ellis CH 1952 A comparative study of the pharmacology of certain Cryptopine alkaloids. J Pharmacol Exp Ther 104 253-263... 

Laudanine, C20H25O4N, was isolated by Hesse. The crude alkaloid is purified by recrj stallisation from dilute alcohol for the removal of small quantities of cryptopine, or it may be dissolved in acetic acid and the solution poured into dilute caustic soda, when this impurity is precipitated and laudanine may be recovered from the filtrate by addition of ammonium chloride. It still contains its isomeride laudanidine, which may be separated by repeated crystallisation of the hydrochlorides, laudanidine accumulating in the aqueous mother liquors. The base crystallises from dilute alcohol, or from a mixture of alcohol and chloroform in rhombic prisms, m.p. 166°, [a]o 0°. It dissolves in solutions of alkali hydroxides, fornung metallic derivatives, which are precipitated by excess of alkali, but is nearly insoluble in solution of ammonia. The salts crystallise well ... 

Haworth, Koepfli and Perkin have shown that, like other alkaloids of the protoherherine series, tetrahydropalmatine is convertible by the general process (p. 302) into an alkaloid of the cryptopine type. The... 

This series of ten alkaloids may appropriately be called the cryptopine sub-group, since the characteristic nuclear structure of the type was first made clear by Perkin s investigation of cryptopine. They are closely related to the profoberberines, with which they are interconvertible by two characteristic reactions, which have been of great value in their investigation. The two alkaloids formerly known as )S- and y-homochelidonines have now been renamed a- and -ofiocryptopines respectively to distin-... 

The formation of (A) and (C) indicates that cryptopine must have in its structure the grouping I, whilst the production of (B) and (D) shows that the alkaloid must also contain the piperonyl ring in the form of grouping II, and from these the structme of anhydrotetrahydromethyl-cryptopine is represented by formula III ... 

The methochloride of (IX) occurs in two forms, identical with the a-and )S-forms of Modihydrocr3T)topine chloride (X). The two chlorides were converted into the two anhydrodihydrocryptopines A and B (p. 297). Of these the A base was oxidised by perbenzoic acid to the amine oxide (XI), m.p. 135° dec.), and this on heating with acetic and hydrochloric acids passed into cryptopine (XII), m.p. 220-1°, identical in all respects with the natural alkaloid. 

Berberine is probably the most widely distributed alkaloid. It and the allied alkaloids palmatine, jatrorrhizine, columbamine and coptisine occur somewhat frequently in the Rhcnadales (list, p. 169) as the tetrahydro-derivatives, but, in the botanical families referred to in the distribution list below, the tetrahydro-derivatives are exceptional and the unreduced alkaloids usual. The associated alkaloids include two members of the aporphine group, domesticine and t odomesticine (p. 315), one member of the cryptopine group, y-homochelidonine (p. 294) and two members of the double woquinoline type, viz., berbamine and oxyacanthine (p. 346). 

Cryptopine and allied alkaloids, pharmacological action, 305 sub up, alkaloids, 284, 294 a-o/loCryptopine 0-homochelidonine), 169,... 

Cryptopine-type indole alkaloid bumamicine (572) has been synthesized from geissoschizine methyl ether (31) (287). In the first step, geissoschizol (34) was prepared, and then cleavage of the C/D ring fusion was carried out by means of ethyl chloroformate. Finally, C-3 carbonyl and 7V-methyl groups were developed by simple oxidation, reduction, and repeated oxidation steps. 

Strong through-space interactions are possible in medium rings. Such interactions have been discovered in certain alkaloids like cryptopine and protopine, which are characterized by atypical properties of their functional groups like low basicity of amino groups and low carbonyl reactivity of carbonyl groups. 

Other alkaloids are codamine, cryptopine, gnoscopine, hydrocotarnine, lanthopine, lauda-nine, laudanosine, meconidine, oxynarcotine, papaveramine, protopine, pseudomorphine, rhoeadine, and tritopine. Many of them occur only in traces, and some are regarded as probable derivatives of morphine. Porphyroxin is said to be a complex combination of several of the alkaloids, and not a proximate principle (Potter, 1910). 

Thus far the pharmacologically investigated alkaloids of this group (protopine, cryptopine, and a-allocryptopine) affect the heart activity. They are active dilators of the coronary vessels (573). After i.v. administration to rabbits and guinea pigs, a slight increase in blood pressure and a greater tendency to the development of cardiac arrhythmia induced by epinephrine are observed. 

The main alkaloid in A. fruticosa is hunnemanine along with allo-cryptopine A, echinata contains mostly cryptopine and berberine (9). 

Janicot et al. presented the separation of opium alkaloids using sub-critical and supercritical fluid chromatography [20]. Carbon dioxide-meth-anol-triethylamine-water mixtures were used as the mobile phase with packed aminopropyl or bare silica columns. The influence of aminated polar modifiers such as methylamine, ethylamine, and triethylamine was studied. Figure 7.15 shows the separation of six opium alkaloids narcotine, papaverine, thebaine, codeine, cryptopine, and morphine on a Lichrosorb Si-60 column. The method gave comparable results with HPLC. 

BicucuUme (AA), cryptopine, hydrastine, corlumine, and related isoquinoline alkaloids (AA) securinine harmaline and related (J-carbohne alkaloids (A) muscimol (A) securinine (AA)... 

Cryptopine was demonstrated to enhance 3H-y-aminobutyric acid (GABA) binding to rat brain synaptic membrane receptors. Using this phenomenon as an in vitro paradigm, cryptopine and other protopine alkaloids may be suggested to have benzodiazepine-like activity [264]. 

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.7.5. Separation of some opium alkaloids Column Nucleosil 10CN (300x4 mm 10), mobile phase - dioxane (79 16 5), flow rate 1.5 ml/min. Peaks cryptopine 5, thebaine 6, noscapine 7, papaverii...

Figure 23.7 Separation of opium alkaloids with supercritical mobile phase [reproduced with permission from J.L. Janicot, M. Caude and R. Rosset, J. Chromatogr., 437,351 (1988)]. Conditions column, 12 cm x 4 mm i.d. stationary phase, Spherisorb NH2, 3pm mobile phase, carbon dioxide-methanol-triethy-lamine-water (87.62 11.80 0.36 0.22),8 ml min pressure, 220 bar temperature, 40.7 C UV detector, 280 nm. Peaks 1= narcotine 2 —thebaine 3 = codeine 4 = cryptopine 5 = morphine.

The synthesis of the parent ring-system of the protopine alkaloids using Perkin s method has been described.224 The preparation of examples of the indeno[l,2-c]isoquinoline ring system (219), exhibited by a rearrangement product of cryptopine, has been described.225 The transformation of protopine to benzophenanthridine alkaloids will be described in Section 3 J. 

The main alkaloids were alio cryptopine and protopine along with lesser amounts of d-corydine, heliotrine, and sanguinarine 118). 

Janicot, J.L. Caude, M. Rosset, R. Separation of opium alkaloids by carbon dioxide sub- and supercritical fluid chromatography with packed columns. Application to the quantitative analysis of poppy straw extracts. J.Chromatogr., 1988, 437, 351—364 [SFC simultaneous cryptopine, morphine, narcotine, papaverine, thebaine]... 

Allocryptopine, benzophenanthridine alkaloids, cryptopine, hunnemannine Allocryptopine. berberine, chelerythrine, protopine, sanguinarine... 

Alkaloid , allocryptopine, bocconine (= chelirubine), bocconoline, chelerythrine, cryptopine, dehydrocheilanthifoline, 41-48... 

Adlumine, alkaloid mp 156°, (-b)-bicuculline, bracteoline, corgoine, corydine, cryptopine, domesticine, gortschakoine, 82-86... 

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