Chelerythrin

Chelerythrine [34316-15-9] M 389.4, m 207°. Crystd from CHCI3 by addition of MeOH. 

Bocconia arborea Wats. Chelerythrine, aZZocryptopine, protopine ... 

Chelerythrine ( ), a- and 3-aZZocryptopine. Chelerythrine. One per cent, in bark none in... 

This sub-group includes four alkaloids, a-homochelidonine, chelidonine, chelerythrine, and sanguinarine, whose nuclear structure and interrelationships (formula I to IV) have been established. Three minor chelidonium alkaloids, oxychelidonine, methoxychelidonine and oxy-sanguinarine, whose association is implied by their names, are included. 

Chelerythrine, C2iHi,04N. H2O. (Items 4, 5, 6, 7, 43, 46, 60 list, p. 169). This base was isolated by Probst from the root of Chelidonium majus. It was probably first obtained in a pure state by Konig and Tietz, from the root of Sanguinaria canadensis. A process for the separation and purification of the alkaloids of Chelidonium majus roots is given by Schmidt and Selled... 

Chelerythrine crystallises from alcohol in colourless, prismatic leaflets, m.p. 207°, containing one molecule of alcohol. The alkaloid absorbs carbon dioxide from the air, becoming yellow. The solutions fluoresce blue when the alkaloid is contaminated with its oxidation product, which is formed by mere exposure of solutions to air. The salts, which are quaternary, are intensely yellow. The hydrochloride, B. HCl. HjO, forms citron-yellow needles, and the sulphate, B. H2SO4.2HjO, golden-yellow needles, sparingly soluble in water the platinichloride, B2. HaPtCl. ... 

Gadamer and Winterfeld ) whose transformation into dihydro- -chelerythrine, and eventually into -ehelerythrine (sanguinarine) is described later. 

The relationship between chelerythrine (II) and sanguinarine (IV) was also established by Spath and Kuffner, who showed that dihydro-chelerythrine (p. 278) and dihydrosanguinarine, C20H15O4N, m.p, 188-9°, prepared from the natural alkaloid, and obviously identical with the dihydro- -chelerythrine of Gadamer and Winterfeld (see above), on replacement of the methylenedioxy-groups by methoxyl groups yielded the same substance, viz., tetramethoxv-A-methyldihydro-a-naphthaphenanthridine (VI). 

Hantzsch 2 gave the name pseudo bases to those carbinols that gave salts with acids by the elimination of water and a simultaneous change of constitution. Such carbinols are common among the nitrogen heterocyclic compounds and the naturally occurring alkaloids e.g., berberine, sanguinarine, chelerythrine. 

The first successful transformation of protoberberines to benzo[c]-phenanthridines was reported by Onda et al. (122,123). Irradiation of the enamines 200 and 195, the Hofmann degradation products of the corresponding protoberberines, in benzene afforded the initial photoproducts 201, which immediately rearranged to the tetrahydrobenzo[c]phenanthridines 202 in 70% yield (Scheme 37). Dehydrogenation of 202 afforded dihydro-chelerythrine (203) and dihydrosanguinarine (204), which were further oxidized with dichlorodicyanobenzoquinone (DDQ) to yield chelerythrine (205) and sanguinarine (206), respectively. 

Scheme 37. Synthesis of chelerythrine (205) and sanguinarine (206) by photocyclization. Reagents a, hv, benzene b, Pd-C, p-cymene c, DDQ, benzene.

Scheme 41. Biomimetic synthesis of chelerythrine (205) and fagaridine (238) via the enamide aldehyde. Reagents a, B2H6 b, H202, NaOH c, PCC d, T1(N03)3, MeOH e, HC1 f, LAH g, MeOH h, NaBH4 i, p-TsOH, toluene j, I2, EtOH.

Lithium aluminum hydride reduction of oxychelerythrine (232) gave 6-hydroxydihydrochelerythrine (235), recrystallization of which in methanol afforded 6-methoxydihydrochelerythrine (agoline) (236). Both compounds have been isolated from plants, but they are probably artifacts arising during isolation. On reduction with sodium borohydride or dehydration with 10% hydrochloric acid, 235 was converted to dihydrochelerythrine (203) or chelerythrine (205), respectively (130,131). 

Similarly, berberine (15) was readily converted to (+)-homochelidonine (264), (+)-chelamidine (262), chelerythrine (205), and dihydrochelerythrine (203) (141). According to this method both hexahydro and fully aromatized benzo[c]phenanthridine alkaloids can be readily synthesized via a common intermediate (e.g., 260). 

Synthesis of all four 8,8a-secobenzophenanthridine alkaloids was carried out chiefly by Baeyer-Villiger oxidation of appropriate benzophen-anthridines (Scheme 32). Thus, arnottianamide (206) was obtained from chelerythrine (210) (172,175), iwamide (207) from N-methyldecarine (211) (168,172), integriamide (208) from avicine (212) (171,172), and isoarnottiamide (209) from nitidine (213) (172,175). The proposed mechanism of this reaction (168,172,175) consists of initial attack of the peroxide ion on the C=N+ double bond followed by rearrangement and hydrolysis. 

The plant is known to contain chelerythrine chloride, which inhibits the aggregation of rabbit platelet in vitro via inhibition on thromboxane formation and phosphoinosi-tides breakdown (30). Chelerythrine, which occurs in members of the family Papaver-aceae, has been reported to inhibit the enzymatic activity of protein kinase C and to exert cell-growth inhibitory effect via the induction of apoptosis in numerous cancer cell lines (31,32). What is the topoisomerase activity of chelerythrine ... 

Chmura SJ, Dolan ME, Cha A, Mauceri HJ, Kufe DW, Weichselbaum RR. In vitro and in vivo activity of protein kinase C inhibitor chelerythrine chlorise induces tumor cell toxicity and growth delay in vivo. Clin Cancer Res 2000 6 737-742. 

Kemeny-Beke A, Aradi J, Damjanovich J, et al. Apoptotic response of uveal melanoma cells upon treatment with chelidonine, sanguinarine and chelerythrine. Cancer Lett 2005, in press. 

Chelerythrine Green-yellow/ - Green-yellow/ ChE in Plm, CW i=5xio5 I =2x1 O 5... 

Fig. 6.15 FAC-MS chromatograms of dual indicators for protein kinase Ca [32]. (a) In the chromatograms, the red lines correspond to a void marker, the blue lines correspond to the substrate-site indicator chelerythrine chloride and the magenta lines correspond to the ATP-site indicator PDl53035. Arrows...

Militante JD, Lombardini JB (1999) Taurine uptake activity in the rat retina protein kinase C-independent inhibition by chelerythrine. Brain Res 818 368-374... 

Chelidonium album L. C. hybridum L. C. majus L. C. serotinum L. Bai Qu Cai (Celandine poppy) (whole plant) Chelidonine, chelidocystatin, protopine, stylopine, allocryptopine, chelerythrine, sparteine, coptisine.33-256-449-497 Anodyne, analgesic, diuretic, antitussive, detoxicant, anticancer. Treat abdominal pain, peptic ulcers, chronic bronchitis, and whooping cough. 

---