Sanguinarine

Patents Concerning Sanguinarine Production in Plant Cell Cultures 

Franke, and L. Lammel. Akademie de Wissenschaften der DDR. Ger. (East) DD 143270, 13-09-1980. Chelidonium majus alkaloids. Chem. Abst. 95, 39333x. 

Furuyo, Jpn. Kokai Tokkyo Koho JP 56/61994 [81/61994], 27-05-1981. Production of opium alkaloids by tissue culture of Papaver. Chem. Abstr. 95, 112023c. 

(2onstabel, W. G. W. Kurz, and U. Eilert. Canadian Patent Application No. 496,984, 5-12-1985. U.S. Patent Application No. 06/889247, 25-7-1986. European Patent Application No. 86309182.3, 25-11-1986. Danish Patent Application No. 5762/86, 1-12-1986. Japanese Patent Application No. 289735/86, 4-12-1986. Semicontinuous production and secretion of phytochemicals by plant cell culture with successive elicitation. Chem. Abstr. 107, 52942z. 

Alkaloid Plant species Type of culture Yield Ref. 

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Schlotterbeck and Watkins also recorded diphylline, m.p. 216°, which Manske suggests is dZ-stylopine (tetrahydrocoptisine), and sanguinarine, which Manske could not confirm. ... 

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. 

On the basis of these results they assigned formula (II) to ehelerythrine, and this was confirmed by the further observation that dihydrocheler -thrine, m.p. 166-7°, on treatment with phloroglucinol and sulphuric acid and subsequent methylation of the dihydric phenolic base so formed, yields tetramethoxy-A -methyldihydro-a-naphthaphenanthridine (VI), m.p. 182-3°, also obtainable from sanguinarine. ... 

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

The nature of the nucleus in chelidonine and sanguinarine was established by Spath and Kuffner,i who showed that both alkaloids on distillation with zinc dust yielded a-naphthaphenanthridine (V), first prepared by Graebe, and on that basis formula (IV) was suggested for sanguinarine. 

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). 

Oxysanguinarine, C2oH430gN, was isolated by Spath, Schlemmer, Schenck and Gempp by chromatographic analysis of blood root alkaloids, and was also prepared by oxidation of sanguinarine nitrate by potassium ferricyanide in alkaline solution. It was purified by crystallisation from... 

Robinson (1934) has elaborated this into a scheme embracing hydrastine, berberine, epicryptopine, corydaline, sanguinarine and homochelidonine, though he points out that dihydroxyphenylalanine is labile and too easily convertible into indole derivatives to be capable of... 

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. 

Figure 11.28 shows densitograms from the separation of Chelidonium majus quaternary alkaloids [114]. It is clearly apparent that multiple development results in better separation of the component bands. Threefold development results in separation or partial separation of eight alkaloid bands (Figure 11.28b), whereas after one run, only four zones — chelirubine, sanguinarine, chelilutine, and chelerithrine... 

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.

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. 

Karp, J.M., Rodrigo, K.A., Pei, P., Pavlick, M.D., Andersen, J.D., McTigue, D.J., Fields, H.W. and Mallery, S.R. (2005) Sanguinarine activates polycyclic aromatic hydrocarbon associated metabolic pathways in human oral keratinocytes and tissues. Toxicology Letters, 158, 50-60. 

Although ajmaline also influences Na+ channels, its activity is to block these channels. This influences the refraction phase of the heart beat and also decreases heart rate. Ajmaline may be used to correct arrhythmic defects. Sanguinarine also influences Na+ ions and particularly inhibits esterase activity. This alkaloid has several other activities in the body and specifically in tissues. Possible applications are linked to the promotion discharge of mucus from the respiratory tract. 

Figure 93. Sanguinarine, an alkaloid from Sanguinaria canadiensis.

Sanguinarine Chelidonium majus Corydalis ophiocarpa Eschscholzia califomica Fumaria cordata Macleaya cordata... 

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