Rauwolfia alkaloids, extraction

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. 

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... 

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 Over a period of a few years, they have been rapidly superseded by synthetic alternatives.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). 

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. 

Reserpine and vincaleukoblastine represent the most important plant-derived medicinals introduced into medicine by our generation, and it is instructive to compare their history with those of morphine and quinine. Descriptions of the use of extracts of plants resembling Rauwolfia may be traced back to ancient Hindu ayurvedic writings. They were used in primitive Hindu medicine for a variety of diseases, including snake bite, hypertension, insomnia, and insanity. The early remedies were used for various other purposes, but it seems clear now that our present day application of Rauwolfia alkaloids in treating hypertension and mental disease was foreshadowed in the folk medicine of the Eastern peoples. 

Reserpine (Fig. 4), an alkaloid extracted from Rauwolfia serpentina, and many other natural or synthetic substances block the storage of monoamines (catecholamines as well as 5-HT) the resulting depletion of the amine stores is accompanied by a rise of acidic metabolites in the urine. This property of reserpine-like compounds to deplete monoamines stores has great experimental and clinical value... 

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. 

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). 

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). 

An old and historically important drug that affects the storage and release of norepinephrine is reserpine. Reserpine is one of several indole alkaloids isolated from the roots of Rauwolfia serpentina] these roots were used in India for centuries both as a remedy for snake bites and as a sedative. The antihypertensive effects of the root extracts were first reported in India in 1918 and in the West in 1949. Shortly thereafter, reserpine was isolated and identified as the principal active agent. Reserpine was the first effective antihypertensive drug introduced into Western medicine, but it has largely been replaced in clinical use by agents with fewer side effects. 

Up to the 1960s, the treatment of atherosclerosis was only symptomatic. [363] Thus, for example for lowering blood pressure, there was used an extract from the snake-shaped roots of Rauwolfia serpentina, which was already known to the ancient Hindus (Fig. 5.149). [364] In 1952, EmU Schlittler (1906-1979) of the Ciba company isolated reserpine as its hypotensive principle, and determined its constitution. In particular, he also recognised the relationship to the large class of yohimbine alkaloids. The first constitutional total synthesis was achieved in 1956 by R. B. Woodward. [365-367] It counts as one of his most notable contributions to modern synthetic chemistry and formed the basis of industrial processes for the synthesis of this drug. In 1989, Gilbert Stork published a stereospecific total synthesis. [368]... 

Alkaloids— basic, medium activity isolation of ergo, opium, rauwolfia, and other alkaloids Antibiotics—neutral isolation, purification Essential oils— basic, neutral removal of terpenes Plant extraction—basic, neutral, acid isolation of active substances... 

Some R. a. have valuable pharmacological properties. They may act centrally (e.g. see Reserpine) or peripherally (e g. see Yohimbine, Ajmaline). In addition to the pure alkaloids or their synthetic analogs, extracts of the drug Radix Rauwolfiae and combination preparations are also used. The drug has been known since early times in Indian folk medicine, and its systematic investigation began in 1930. 

An active alkaloid that is extracted from the root of shrubs of the genus Rauwolfia, and used tis a tranquilizer or sedative. It is also used as an antihypertensive dmg, in the treatment of high blood pressure, various mental diseases, and tension. 

This alkaloid is similar to reserpine except that the reserpic acid moiety of the molecule is esterified with trimethoxycinnamic acid rather than with trimethoxybenzoic acid. A non-aqueous titration similar to that given above is applicable (1 ml 0 05N 0-03174 g), or the colorimetric nitrite procedure may be applied. If the sample is thought to be contaminated with some of the other alkaloids of rauwolfia (less weakly basic), an extraction procedure can be applied followed by colour development as in the recommended method above. An aliquot of a suitable extract is diluted with 0-5N sulphuric acid and the aqueous ethanol is then extracted with trichloroethane which is discarded. The rescinnamine is then separated from other alkaloids by extracting the acid solution with chloroform and a suitable aliquot of the chloroform solution, containing 100 to 300 fxg of rescinnamine is evaporated and used for the colour development stage. The rescinnamine content is obtained from a standard curve prepared using a solution of rescinnamine in 95 per cent ethanol. 

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