Rauwolfia bases

Of relevance from a practical point of view are publications dealing with the t.l.c.-quantitative analysis of twelve Rauwolfia bases, " t.l.c.-colour reactions for analysis of 38 indole alkaloids from some Vinca species, the quantitative determination of Cinchona quinoline alkaloids by t.l.c.-differential spectrophotometry, and the high-speed liquid-liquid chromatography of ergot alkaloids " and Mitragyna alkaloids. ... 

Materials can be classified as hard, intermediate, soft, or fibrous materials (e.g., glycyrrhiza and rauwolfia) based on Moh s Scale. Fibrous materials require cutting or chopping action and usually cannot be reduced in size effectively by pressure or impact techniques. Before selecting and optimizing a size reduction process one needs to know the properties of the material and the characteristics of a mill. The important material properties (5,10) are as follows ... 

The psychoactive constituents of rauwolfia are alkaloids classified in three groups (1) weakly basic indole alkaloids, (2) intermediate basic indoline alkaloids, and (3) strong anhydronium bases. Approximately 50 alkaloids have been identified, but the principal indole alkaloids... 

From the roots of Rauwolfia cambodiana, the alkaloids pelirine and ajmaline have been isolated (73). The alkaloids akuammicine, akuammi-cine Nb-oxide, akuammicine Nb-methiodide, pseudoakuammigine, and tubotaiwine have been newly recorded from the root bark of Alstonia scholaris R.Br. (Apocynaceae) echitamine is isolated as the major alkaloid, along with Nb-demethylechitamine, as well as three unidentified echitamidine isomers, and other known alkaloids. The stems of the same plant yielded echitamine, Nb-demethylechitamine, tubotaiwine, pricri-nine, and other unidentified echitamidine isomers (81,82). Apart from the alkaloids in the heteroyohimbine group from roots of Rauwolfia serpentina, a new base, named ajmalimine (73) (53), and ajmalinimine (74)... 

Threshed roots of Rauwolfia canescens L. extracted with 5% solution of acetic acid at room temperature for 24 h. Then extract was decanted to flask. This extract was alkalified with ammonia (alkaloid salts were converted to alkaloid bases). The obtained thus method solution was extracted with chloroform 3 or more times. Then chloroform extract was chromatographed on column through Al203 sorbent. After chromatography ajmalin was obtained, which had melting point at 205°C (recyrstallization from methanol). 

Material Indole-based alkaloid in Rauwolfia serpentina. ... 

Material Major active indole-based alkaloid in Rauwolfia spp. 

Material Yohimbine is one of several indole-based alkaloids found in Corynanthe yohimbe, Rauwolfia serpentina, and several other plants. 

Two further alkaloids have been obtained from the leaves of Rauwolfia reflexa Teijsm. et Binn.93 One of these was identified as purpeline (163), a structure which was confirmed by its demethylation to mitoridine (164). The second base, reflexine, C2iH26N202, m.pt. 260 °C, [a]D + 126°, exhibits the spectra of a dihydro-purpeline, and can in fact be prepared by the reduction (NaBH4) of purpeline. Reflexine (165) is thus the C-17 epimer of seredamine (166) and has not previously... 

In spite of some discrepancies between the reported physical constants, it seems more than likely that deacetyldeformylakuammiline (Base A), isolated from Rauwolfia vomitoria,91 is identical with strictamine (168), in view of its reported chemical properties. 

A new weak base, neonor-reserpine, from Rauwolfia vomitoria, is regarded as a stereoisomer of psuedoreserpine 45 since the new base appears to have the epiallo stereochemistry, it must differ from pseudoreserpine in the stereochemistry at one or more of the positions C-16, C-17, and C-18. 

Another fruitful means of identifying pharmacologically active natural products has been that of folk law remedies, many of which are plant products. Typical examples include alkaloids, such as atropine (from plants of the Solanaceae family, known to the ancient Greeks) and reserpine (from Rauwolfia serpentina, the snakeroot), which is popular in India as a herbal remedy for use as a tranquilizer or antihypertensive. Other chapters in the book relate to stigmines (based on phy-sostigmine, an anticholinesterase alkaloid from the Calabar bean in West Africa) that are used to treat Alzheimer s disease (Chapter 11-12), and opioid receptor ligands (based on morphine, the most important alkaloid of the opium poppy) for pain relief and as antitussives (Chapter 11-11). 

For laboratory purposes, methanol is the usual solvent, and procedures based on its use have been described in detail (21, 39, 81). Of great practical usefulness for the separation of the weakly basic fraction is the solubility of certain alkaloidal acetates in chloroform, e.g., reserpine, ajmalicine, and aricine, whereas other acetates are insoluble in this solvent, e.g., ajmaline, yohimbine, and a-yohimbine. Since the anhyd-ronium alkaloids are extremely strong bases, they can only be extracted into an organic solvent in their tertiary base form at pH 11. For industrial purposes, the best process extracts water-moistened Rauwolfia root with hydrocarbons such as benzene, toluene, or xylene. In this procedure, only the weak bases are extracted. No complicated separation processes are involved, and reserpine is obtained in high yields (122). 

The occurrence of reserpine has been reported from all Rauwolfia species, with the exception of about half a dozen in which it is probably present in minute amounts. Renoxidine, the A-oxide of reserpine, has been isolated from R. vomitoria, R. serpentina, and R. canescens, and it may not be a natural product, since it could have been derived by autoxi-dation of the tertiary base which is abundant in these plants. If it was an artifact, the occurrence of other analogous A-oxides should have been noted, but so far the only other recognized case is raujemidine A-oxide, which is found along with the parent alkaloid, raujemidine (a minor base of R. canescens). In contrast to reserpine, deserpidine and rescinnamine are of restricted distribution, each being recognized so far in about ten species only. 

The roots of a variety of Rauwolfia vomitoria Afzel. collected in Guinea yielded a small amount of a base, seredine, C23H30O5N2, mp 308°, t ]D- 1° (CHCI3), and pK 6.69 (33). 

Rauwolfia species have been the source of other bases closely related to ajmaline, and the structures of some of them can be regarded as trapped intermediates of the plausible, but as yet still hypothetical, biogenetic route to the major alkaloid, ajmaline itself. 

Pleiocarpamine has been found in the bark of Alstonia vitiensis (Seeman) var. novo ebudica monachino, and 10-methoxygeissoschizol, a-yohimbine, and alstonine in the leaves and stems of Rauwolfia obscura the stems also contain tetrahydroal-stonine and an anhydronium base which, unfortunately, decomposed in the mass spectrometer and was obtained in insufficient amount for structure elucidation. 

The deep-yellow base serpentinine, first isolated from Rauwolfia serpentina Benth. ex Kurz and later from other related species, possesses the molecular formula C42H44O6N4, based on elemental analyses and molecular weight determinations. The anhydrous compound is hygroscopic and crystallises with 1—2 moles of water. The analyses of a number of salts agree with this formula. 

Serpenticine is a new anhydronium base isolated from Rauwolfia... 

Peraksine, norpurpeline (149), dihydronorpurpeline, endolobine (150), purpeline, seredamine, nortetraphyllicine, normacusine B, and desacetyl-picraline have been found in the stem bark of Rauwolfia cumminsii j two minor bases were tentatively identified as O-methylnormacusine B (17-methoxysar-pagan) and its Nb-oxide, and a third, as yet unidentified, is probably also a sarpagan derivative. Sarpagine, normacusine B, purpeline, norpurpeline, norseredamine, nortetraphyllicine, and 10-hydroxynortetraphyllicine occur in R. vomitoria stems an unknown base was provisionally formulated as (151), but the stability of the 7,17-bond in such a structure is very much in doubt. 

Bark may contain up to 6 % total alkaloids, of which 10-15 % is yohimbine [120]. Concentrations of yohimbine in commercial products ranged from less than 0.1 to 489 parts per million (ppm) compared with 7,089 ppm in the authentic material. The alkaloid yohimbine also is obtained from Aspidosperma quebracho-bianco and Rauwolfia serpentina [121]. Its interest outside the African continent was first recorded in Germany, where yohimbine, the main alkaloid of the drug and also known as aphrodine, quebrachine, or corynine, was isolated for the first time by Spiegel in 1896 [130]. Recent advancements in the development of yohimbe-based... 

A simple version of this scheme of commercial importance is illustrated by obtention of reserpine (pA 6-06) from the roots of Rauwolfia vomitoria. The groimd roots are extracted with benzene which is washed with aqueous acetic acid to remove the strong bases, and concentrated whereupon the reserpine crystallizes out. 

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