Sanguinarine from

The constitution of a number of alkaloids has not as yet been definitely established. Among these are aconitine from aconite, delphinine from larkspur, jervine and protojervine from veratrum viride, cevadine from sabadilla seed, lobeline from lobelia, the curare alkaloids from Chondro-dendron tomentosum, sanguinarine from sanguinaria, and many others. 

Chelidonine, dihydrochelerythrine, and dihydrosanguinarine have been isolated from Glaucium vitellinum,109 chelerythrine and sanguinarine from Corydalis ophiocarpa,71 oxysanguinarine and 8-methoxysanguinarine from Fumaria indica,125 a new base corynolamine (149 R = CH2OH) from Corydalis incisa,379... 

P450 enzyme, protopine 6-hydroxylase, to yield an intermediate that rearranges to dihydrosanguinarine (40). This intermediate also serves as the precursor to the benzo(c)phenanthridine alkaloid macarpine (Fig. la). The copper-dependent oxidase dihy-drobenzophenanthridine oxidase, which has been purified (41, 42), then catalyzes the formation of sanguinarine from dihydrosanguinarine. 

Important drugs have been derived from two plants common in the woodlands of the eastern United States. One is etoposide (an anticancer drug) based on the podophyllotoxin found in Podophyllum peltatum,415 The second is sanguinarine (from Sangulnarla canadensis), which is used for treatment of periodontal disease. A common fence lizard of the western United States, Sceloporus occidentalis, has something in the blood that kills the bacteria responsible for Lyme disease.416... 

The release of sanguinarine from the cells into the medium after elicitation was used as the basis for the design of an industrial process for production of the alkaloid 72,99,487,492,493). As the cells of P. somniferum remain viable after a 72-hr exposure to a fungal elicitor, it is possible to recycle the cells after induction of alkaloid biosynthesis. Because about 40-60% of the alkaloid is released to the medium, a simple change of medium is sufficient to collect the alkaloid and to recover viable cells. By a repeating sequence of elicitation and medium replenishment, a semicontinuous production process was obtained. Such a process was also developed for alkaloid production in Catharanthus roseus, Ruta grave-olens, and P. somniferum cell cultures using different elicitors (99). 

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. ... 

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... 

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... 

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 1 is the prototype of benzophenanthridine alkaloids which occur frequently in plants of the family Papaveraceae. It has anticancer activity and has become of commercial interest because of its antibacterial properties. It is known from biosynthetic studies that protopine 2 is a metabolite on the pathway to sanguinarine, and recent work has shown that a microsomal cytochrome P-450 NADPH dependent enzyme will hydroxylate protopine... 

The possible relationship of sanguinarine to glaucoma in epidemic tropical hydropsy which is frequent in India has been referred to (666, 677, 687). The oil from Argemona mexicana L., whose seeds... 

S)-Reticuline is a branch-point intermediate in the biosynthesis of most BAs. Most work has focused on branch pathways leading to the benzophenanthridine (e.g., sanguinarine), protoberberine (e.g., berberine), and morphinan (e.g., morphine and codeine) alkaloids.19 Most enzymes involved have been isolated, many have been purified, and four corresponding cDNAs have been cloned.19 The first committed step in benzophenanthridine and protoberberine alkaloid biosynthesis involves the conversion of (S)-reticuline to (5)-scoulerine by the berberine bridge enzyme (BBE) (Fig.7.2). BBE was purified from Berberis beaniana,20 corresponding cDNAs were cloned from E. californica and B. stolonifera,21 22 and BBE genes have been isolated from P. somniferum and E. californica.23,24... 

Alkaloids derived from phenylalanine Sanguinarine Papaver bracteatum Fungal elicitor CC 466.467... 

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