Protopine alkaloid allocryptopin

Bentley and Murray (201) reported another method for synthesis of protopine alkaloids allocryptopine (392) and cryptopalmatine (395) from tetrahydroprotoberberine /V-oxides (35a and 400) through oxidative rearrangement with potassium chromate (Scheme 73). 

Certain berberine alkaloids can also be directly prepared from the appropriately substituted protopine alkaloid by photolysis in ethanol.387 Berberine itself (359) is obtained in this way from a-allocryptopine (360), and similar preparations of epiberberine and coptisine have been recorded. 

Macleaya cordata (Papaveraceae) contains alkaloids in alkaloid cells filled with yellow to orange-red liquid (27). Alkaloid cells were observed as bluish yellow fluorescence in transverse and longitudinal sections of roots of M. cordata with a fluorescence microscope (48). Four main alkaoloids are known to be present in roots of M. cordata, namely, sanguinarine and chelerythrine, which are benzo[c]phenanthridine alkaloids red and yellow in color, respectively, and protopine and allocryptopine, which are colorless protopines. The liquid from colored cells in M. cordata roots was aspirated into the microtrap under a microaspiratoscope. The liquid remaining in the capillary and the connector tubes between the capillary and microtrap was washed into the microtrap with the solvent used for HPLC analysis. It was shown that the liquid of colored cells contained all four alkaloids, judging by comparison with authentic samples on HPLC. Therefore, HC proved the colored cells to be the alkaloid cells named by Neumann and Muller. 

The alkaloid contents in a single alkaloid cell from M. cordata roots of three different thicknesses (age 1-2 years) were determined as follows. The liquid from various numbers of alkaloid cells (Table II) was removed uniformly and collected in the microtrap. The liquid in the capillary and connection tubes was washed into the microtrap to make a certain definite volume for analysis. Quantitative analysis of each alkaloid was carried by preparing a calibration graph (4). Figure 3 shows the HPLC chromatogram of alkaloids from the alkaloid cells. The content of each alkaloid per single alkaloid cell in tissues from three different thickness of roots and its ratio are shown in Table II. The liquid in colorless cells contained only a minute amount of protopine and allocryptopine (Fig. 3). The thicker the roots, the more alkaloids were contained in a single alkaloid cell. In any thickness of root, the content of protopine-type alkaloids exceeded that of benzo[c]phenanthridine-type alkaloids. The ratio of the former to the latter was almost steady over 5 mm of root thickness (86-87%). The ratio of alkaloids in methanol extracts of the same fresh samples (thickness 5 mm) was determined by HPLC (Table III). The ratio of protopine-type alkaloids in the methanol extracts ( 80%) was less than that in the liquid from the alkaloid cells ( 87%). This was because the liquid in alkaloid cells near the cambium were picked up more than that in center cells (pith). Thus, intracellular components scattered in different places are analyzed qualitatively and quantitatively in situ by HC. 

Fig. 3. HPLC chromatograms of cell liquid in Mackaya cordata root. Column NOVA-pack C g (5p.), 8 mm x 10 cm eluent 0.1 iV tartaric acid (containing 0.125% sodium dodecyl sulfate)— acetonitrile, 45 55 at 2.0 ml/min detection UV, 285 nm. (a) Alkaloid (colored) cell, (b) Colorless cell. Peaks a, protopine b, allocryptopine c, sanguinarine d, chelerythrine.

Allocryptopine was demonstrated to enhance 3H-y-aminobutyric acid (GABA) binding to rat brain synaptic membrane receptors. Using this phenomenon as an in vitro paradigm, allocryptopine and other protopine alkaloids may be suggested to have benzodiazepine-like activity [175]. 

Alkaloid MR-1, MR-3, allocryptopine, coptisine, corysamine, magnoflorine, papaverrubine D and E. protopine, rhoeadine Alkaloids MR-1 and MR-3, allocryptopine, coptisine, corysamine, magnoflorine, papaverrubine D, protopine Alkaloids MR-1 (C Hi O), MR-2, MR-3, and MR-4, allocryptopine. amurensinine methohydroxide, coptisine, magnoflorine, papaverrubine D and E, protopine, rhoeadine ( )... 

Allocryptopine, C21H23O6N, like protopine occurs in two allotropic modifications, the a-form melting at 160° and the /3-form melting at 170°. The older names of and 7-homochelidonine were based upon an assumed relation to chelidonine and are no longer acceptable. It is readily separable from protopine, with which it is nearly always associated, by reason of the fact that its hydrochloride and nitrate are readily soluble in water. It may also be separated from many associated alkaloids by extracting an aqueous solution of their hydrochlorides with chloroform (34). The protopine alkaloids remain in the aqueous phase. 

The species of the genus Glaucium Toum. are characterized by the presence of aporphine and protopine alkaloids in addition to protoberberines and benzophe-nanthridines (Tables XVII and XVIII). Platonova et al. (110) isolated corydine (136) from G. squamigerum as the major alkaloid in addition to a smaller amount of protopine (309) and allocryptopine (310). In G. oxylobum, the major alkaloid was corydine together with protopine and allocryptopine (107). In contrast, Slavik et al. (108) isolated allocryptopine (310) and protopine (303) as the... 

Fig. 36.3 Chemical structures of sanguinarine and coptisine and CZE separation of seven alkaloids in an extract of Chelidonium majus L. Peaks (7) sanguinarine, (2) coptisine, (3) chelerythrine, (4) stylopine, (5) chelidtmme, (6) protopine, (7) allocryptopine, and (x) unknown component. Conditions 20 mM phosphate buffer, pH 3.1. Separation capillary 75 pm, i.d. uncoated fused silica, 50 cm in length (40 cm effective length). Applied voltage 16 kV. Light-emitting-diode-induced fluorescence (LED) excitation wavelength 280 nm (Modified from reference [14])...

The seeds of A.mexicana may yield up to 60% oil (Murav eva and Bui 1974), which may contain up to ca. 0.9% alkaloid. Sarkar (1948) isolated the benzophen-anthridine alkaloids sanguinarine (6), which comprised 5%, and dihydrosanguinarine (7), which accounted for over 85%, of the total alkaloid present. Seeds from Vietnamese plants when grown in Pyatigorsk, in southern Russia between the Black Sea and the Caspian Sea, yielded oil containing 0.35% sanguinarine (6) and 0.31% of the protopine base allocryptopine (8a) (Bui 1974). 

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. 

Additional results are that (-)-(5)-scoulerine (68) is a precursor for san-guinarine (77) and chelerythrine (78) and labelled (-)-(5)-stylopine (71) is incorporated into coptisine (72). [N-methyl8- H]Stylopine methochloride [as (70)] afforded chelidonine (76) and protopine (73) essentially without change in isotope ratio and must thus be considered as implicated on the pathway to both alkaloids. (The same conclusion for protopine has been reached independently. ) On the other hand radioactive nandinine (79) failed to label chelidonine, stylopine, or protopine, suggesting that the alternative (69) may be an intermediate instead. In agreement with other work (5)-reticuline (67) and (5)-scoulerine (68) were much better precursors than the i -isomers for protopine (73), and incorporation of (68) resulted in complete loss of tritium label from C-14. Allocryptopine (81) was well labelled by radioactive isocorypalmine (82) (which also serves as a precursor for narcotine see below). The combined results lead to the pathways shown in Scheme 3. 

Of the seven alkaloids isolated from this plant four were identified as protopine, ophiocarpine, a-allocryptopine, and berberine (62). 

Allocryptopine, chelamidine, chelamine, chelidamine[( — )-stylopine], chelidonine, chelerythrine, chelilutine, chelirubine, coptisine, corysamine, oxysanguinarine, protopine, sanguinarine, sparteine Capaurme + sendaverine (Alkaloid F-28) = Corpaverine Columbamine, coptisine, dehydrocorydalline,... 

Alkaloid AA-1 (C19H21NO4X AA-2 (C20H21NO5), AA-3, allocryptopine, berberine, chelerythrine, norchelerythrine, norsanguinarine, protopine, sanguinarine, (-)-scouIerine, (—)-0-scouIerine methohydroxide6 Allocryptopine, berberine, coptisine, protopine, sanguinarine... 

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

Allocryptopine, berberine, chelerythrine (—Bocconia alkaloid P 61), columbamine, coptisine, corysamine, (-) isocorypalfnine, S3, 49, SO papavemibine E, protopine, rhoeadine, sanguinarine... 

Alkaloids mp 189° and 196°, allocryptopine, chelerythrine, corlumine, dihydrosanguinarine, protopine, sanguinarine, 84, 141... 

Allocryptopine, chelerythrine, ( )-chelidonine (= diphylline), cheiirubine, coptisine, corydine, dihydrochelerythrine, glaucine, 184, 185 glauvine, isoboldine, isocorydine, O-methylatheroline, protopine, sanguinarine, and quaternary bases of the benzophenanthridine alkaloids... 

Alkaloid MR-1, allocryptopine, berberine, coptisine, corysamine, cryptopine, isorhoeadine, papaverrubine A, C. D. and E, protopine, rhoeadine... 

These alkaloids, chelidonine, homochelidonine, methoxychelidonine, chelerythrine, and sanguinarine, are found in the Chelidonieae tribe of the Papaveraceae family as well as in the genus Glaudum of the same family (tribe-—Papavereae). They are always accompanied by protopine, and sometimes by allocryptopine and the protoberberines. 

The investigation of the herbarium samples from Iraq was carried out (65). Papaver acrochaetum yielded rhoeagenine 404) as the major alkaloid. The major alkaloids of P. curviscapum were protopine (309) and allocryptopine (310). The major alkaloid of Iraqi P. persicum and of P. armeniacum was identified as the glycosidic alkaloid floripavidine (119), which had been first reported from P. floribundum. For the infraspecific variation of the alkaloids of the section Miltantha, see also Ref. 64. 

The only representative of the genus Hunnemannia A. Juss., which is closely related to the genera Eschscholtzia, Dendromecon, and Petromecon, is Hunnemannia fumariaefolia Sweet, native to Central America. In the aerial part of this plant, the major alkaloid is hunnemanine (312) (Tables XXXVIII and XXXIX) and in the roots, protopine (309), hunnemanine, and allocryptopine (310). Cyclanoline (245) represents the main component of the quaternary alkaloid fraction of the aerial part and the roots. 

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