Rauwolfia extracts

More interesting is the pharmacology of ajmaline (37), which is available in large quantities as a by-product of the reserpine extraction. Detailed pharmacological studies seemed to be more than justified because reserpine did not possess all the pharmacological effects of crude Rauwolfia extracts. Ajmaline was compared with quinidine and studied clinically in cardiac arrhythmias,... 

Rauwolfia extract Rauwolfia serpentina. See Rauwolfia serpentina extract Rauwolfia serpentina extract CAS 90106-13-1 EINECS/ELINCS 290-234-1 Synonyms Rauwolfia extract Rauwolfia... 

If the active principle or the group of active substances in the extract has been identified — such as reserpine in rauwolfiae extract or anthraquinones in senna extract — then the other substances contained are, at least from the point of view of the analyst, considered to be of secondary importance. These extracts have a permitted variabifity of the defined range of constituents and it should not exceed a numeric difference of +5% (more than +5% in rare cases). 

There is a similarity between the use of opium with its complex mixture of alkaloids for the treatment of diarrhoea and the use of Rauwolfia serpentina extracts for the treatment of hypertension. The alkaloid combination of the Rauwolfia extract is more effective and better tolerated than reserpine alone because the effects of the centrally acting reserpine are facilitated by other alkaloids which are capable of causing dilation of peripheral blood vessels. 

Thus it appears in these two particular cases of opium and of Rauwolfia extract that the whole is better than its parts. 

The 3,4,5-trimethoxycinnamic ester of methyl reserpate is also present in Rauwolfia plants and obtainable in purified form therefrom by extraction as described in U.S, Patents 2,974,144 and 2,876,228. 

Rauwolfia plants, by extraction Deserpidine Rescinnamine Reserpine... 

By extraction from the pulverized roots of Rauwolfia serpentina (L.) Beuth. 

In 1952 reserpine, an alkaloid extract from the Indian snakewort plant, Rauwolfia serpentina, which had been used in that country to treat madness , was first tried in schizophrenia. The beneficial impact on patients and the hospital wards was dramatic, as was that a year later of chlorpromazine, a phenothiazine derivative and haloperidol, a butyrophenone. These latter two drugs and closely related derivatives remained the mainstay of therapy for almost 40 years. 

Reserpine A drug extracted from Rauwolfia serpentina which was once clinically used in the treatment of essential hypertension and schizophrenia. 

Coincidental with the above developments, biomedical scientists in pharmaceutical companies were actively pursuing purified extracts and pure compounds derived from plants and animal sources (e.g., digitalis, rauwolfia alkaloids, and animal hormones) as human medicaments. Analogs and derivatives of these purified substances were also investigated... 

HPLC 50% methanol in water (jBondapack C-18 Rauwolfia grandiflora/ bark ethanol extract booneinand isoboonein m... 

Reserpine, an alkaloid extracted from the roots of an Indian plant, Rauwolfia serpentina, was one of the first effective drugs used on a large scale in the treatment of hypertension. At present, it is rarely used owing to its adverse effects. 

The rauwolfia alkaloids are now hardly ever prescribed in the UK, either as antihypertensives or as tranquillizers. Over a period of a few years, they have been rapidly superseded by synthetic alternatives. Reserpine has also been suggested to play a role in the promotion of breast cancers. Both ajmalicine (= raubasine) (Figure 6.76) and ajmaline (Figure 6.82) are used clinically in Europe, though not in the UK. Ajmalicine is employed as an antihypertensive, whilst ajmaline is of value in the treatment of cardiac arrhythmias. Ajmalicine is also extracted commercially from Catharanthus roseus (see page 357). 

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). 

Reserpine is isolated from its plant producers by using a nonaqueous solvent process, using, for example, boiling methanol extraction of the African root Rauwolfia vomitoria. Naturally, these extractions are carried out under countercurrent methods. The methanol extract is concentrated and acidified with 15% acetic acid and then treated with petroleum naphtha to remove impurities. Extraction is made using ethylene dichloride. The solvent is neutralized with dilute sodium carbonate, evaporated to drive off the ethylene dichloride, and further evaporated to crystallize the crude reserpine crystals that are then crystallized. 

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). 

Extensive use of column chromatography has been necessary to separate the Rauwolfia alkaloids, and in this connection attention is drawn to a publication which concerned itself with the more refined technique of gradient elution chromatography (123). Paper chromatography has been used extensively for analytical, fractionation, and identification purposes (124, 15). This tool is not particularly useful for the assay of crude extracts, since certain alkaloids show up clearly whereas others cannot be resolved. More information as to specific alkaloidal composition is better obtained from more highly purified fractions. 

Draw a stepwise mechanism for the following reactions, two steps in R. B. Woodward s classic synthesis of reserpine in 1958. Reserpine, which is isolated from the extracts of the Indian snakeroot Rauwolfia serpentina Benth, has been used to manage mild hypertension associated with anxiety. 

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