DE1062889B - Process for obtaining a new cardiac active substance from Bowiea volubilis Harvey - Google Patents

Description

The plant Bowiea volubilis Harvey contains, among others in the onion, several for medicinal purposes Purpose useful substances, especially cardiac glycosides, such as. B. Bovoside A, B, C, D, E etc. Several of these substances have already been found in the onion and other parts of Bowiea volubilis Harvey won. It is Z. B. known that by extracting the dried pulverized several times Bowiea volubilis drug with methanol, concentration of the combined extracts, precipitation of the added Mucilages with acetone and by adsorption on aluminum oxide and subsequent elution from the methanol-acetone solution two crystallized glycosides with melting points of 140 ° C and 300 ° C.

In the plant Bowiea volubilis Harvey, another, previously unknown substance has now become found and isolated. This substance, which was given the name "Bovogenin A", is the aglycon des dykosids Bovosid A.

The present. The invention now relates to a method for obtaining a new heart-active substance, namely Bovogenin A, from Bowiea volubilis Harvey, which is characterized in that the plant or its parts are extracted with water or with a water-containing, water-miscible organic solvent and the The extract is treated with lead hydroxide, whereupon the extract freed from the precipitate is freed from the organic solvent and extracted with a water-immiscible organic solvent, whereupon the ¹ active ingredient is obtained in crystalline form from the organic phase.

As a starting material for carrying out the present process, either parts of the Plant Bowiet volubilis Harvey or the whole plant in fresh "(water-containing) or dried Use form. Living ones are particularly suitable Bulbs of Bowiea volubilis Harvey: it is indicated ;, to finely shred the starting material, e.g. B. by grinding or crushing. When using voii fresh onions it is advisable to take the juice from first. to separate the onions, for example by Pressing or centrifuging, and from the solid onion residues the last remnants of the to be obtained Extract substance, for example by extraction with water or with a; hydrous, organic solvents miscible with water! The extract obtained can then be mixed with the onion juice be united. Instead of separating the onion juice and extracting the residue first, However, you can also mix the chopped onions directly with water or with a water-based one with Water miscible organic solvent extra process for extraction

a new heart active substance

from Bowiea volubilis Harvey

Applicant: Dr. Alfred Katz, Basel (Switzerland)

Representative: . :

Dipl.-Ing. F. Weicbmann and Dr.-Ing. A. Weickmänn, Patent Attorneys, Munich 2, Brunnstr. 8/9. .

Claimed priority: Switzerland of March 8, 1954.

Dr. Alfred Katz, Basel (Switzerland), has been named as the inventor.

to be in a relationship. Lower aliphatic alcohols are suitable as water-miscible organic solvents; especially Riethanoi and ethanol ·. . ;

The water-containing extract obtained by extracting the vegetable starting material in the manner described above is then treated with lead hydroxide, preferably with freshly precipitated lead hydroxide, in order to precipitate organic acids, in particular tannic acids, from the extract or the liquid. After the precipitate has been separated ^{off, the solution containing 1 is} expediently neutralized against litmus, for example with sulfuric acid, hydrochloric acid or another appropriate acid. It is advisable to concentrate the neutralized solution before further processing. · · .- ■. . -. _:

From the solution obtained you can directly one Produce ether extract. However, depending on the type of starting material used, it can be advantageous be certain impurities, e.g. B; water-soluble carbohydrates, to remove from the solution. -To this one Purpose, the solution is expediently with an organic solvent or a mixture of organic Solvents in which the impurities are insoluble or sparingly soluble, e.g. B. with. one Chloroform-ethanol mixture, extracted. The active substance to be obtained goes into the organic Phase over. The chloroform-ethanol extract obtained can then be evaporated to dryness, whereupon the residue obtained is dissolved in water.

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taken and the mixture can be extracted with ether. From this raw ether extract one can a crude crystallizate is obtained by suitable treatment. Pure crystalline Bovogenin A can be obtained by recrystallization of the raw crystals from an organic solvent, such as. B. ethanol, methanol, Acetone or a mixture of these solvents. will.

The solution freed from organic acids by means of lead hydroxide can also be used without the detour processed directly via the chloroform-ethanol extract, e.g. B. by neutralizing and Constrict. The substance to be obtained is expediently extracted from the concentrated solution by shaking it out absorbed into ether. This raw ether extract can be used in the manner described above Obtain crystals of Bovogenin A.

If the raw ether extract contains bovoside A or other impurities in addition to bovogenin A, so it is advisable to engage in another cleaning operation before isolating the bovogenin. This purification is preferably carried out by chromatography, for example using of aluminum oxide. '

Bovogenin A is easily subject to autoxidation in air because it contains a labile aldehyde group. This auto-oxidation is promoted by light. It has therefore proven to be expedient to carry out the individual operations of the present process partly or exclusively in an inert atmosphere, for example in a nitrogen atmosphere. This can significantly increase the yield of Bovogenin A. ^L It is also advisable to carry out individual process steps or all operations under a light shield.

The product obtained by the present process has a melting point of 247 to 262 ° C. and has the gross formula C ₂₄ H ₃₂ O ₅ and the optical rotation [α] ² _O ² = 0 ° ± 4 ° (c = 0.500 in methanol) . With 84% sulfuric acid, the product gives a color reaction which proceeds from green, green-yellow and yellow to ocher with a pale pink border;

The following example is intended to show how the inventive Process can be carried out in practice.

! example

a) 100 parts of Bowiea volubilis Harvey onions are finely ground or mashed. The resulting pulp is squeezed out sharply and the residue from the press is extracted at room temperature or lower temperature under nitrogen by shaking or stirring with 20 parts of dilute methanol (or ethanol) for about an hour. After each extraction, it is squeezed sharply. The alcoholic extracts are combined with the pressed juice. The pressed juice and alcoholic extracts until further processing atmosphere in the cold (5 ⁰ C) under nitrogen and stored under protection from light.

b) For the extraction of a dry form Drug is proceeded as follows:

1160 ml of water are added to 580 g (dry weight) of dried and chopped onions of Bowiea volubilis Harvey. The mixture ^is: k ⁱ shaken hour and then hot pressed. In the same way, it is extracted once more with 1160 ml of water and twice with 580 ml of water each time. The extractions are. carried out in a nitrogen atmosphere. The aqueous solutions obtained are stored in the cold (5 ° C.) under nitrogen and protected from light until further processing.

The combined, liquid extracts obtained according to a) or b) are mixed with freshly precipitated neutrals Lead hydroxide shaken under nitrogen for 1 hour. The lead precipitate is then filtered through a kieselguhr filter sucked and the filter washed with 1 to 2 parts' of the solvent used for the extraction. The filtrate is treated with dilute sulfuric acid until it reacts neutrally against litmus added, if necessary filtered again and then added evaporated to 12.5 parts under reduced pressure in a stream of nitrogen at a bath temperature of about 45 ° C.

The aqueous concentrate is four times with 10 parts each a mixture of 6 parts of chloroform and 4 parts of ethanol in a nitrogen atmosphere.

The Chlorofonn-Ethanol extracts are under reduced pressure in a stream of nitrogen until

Evaporated ao the presence of a thick honey. This is rubbed with 2 parts of water and four times with 5 parts of ether in each case shaken out in a nitrogen atmosphere. The ether solutions are used twice 0.05 part of 2N soda solution and once with 0.05 part Washed water, dried over sodium sulfate and then evaporated to dryness. The dry residue is rubbed with about 0.5 part of ether. The essential solution is poured off. From the undissolved granular residue is obtained by crystallization from methanol, ethanol, acetone or a mixture this solvent obtained a raw crystallizate with ether or a similar solvent, from which pure Bovogenin A is obtained by further recrystallization.

If the extract also contains bovoside A, it turns out to be necessary to chromatograph the raw ether extract, z. B. with alkali-free aluminum oxide to clean. The ether extract is used in a solvent mixture consisting of equal parts of benzene and chloroform and dissolved on a Poured aluminum oxide column (20 times the weight of the ether extract). By washing out the Columns with the same solvent mixture (300 parts to 1 part of ether extract) are undesirable accompanying substances eluted. The bovogenin A is then eluted with chloroform. Only the first fractions included Bovogenin A, while the subsequent fractions contain Bovoside A.

In order to avoid the autoxidative decomposition of the sensitive Bovogenin A, it is necessary during recrystallization to work quickly and to carry out all operations under light protection if possible.

The Bovogenin A obtained has a melting point of 247 to 262 ° C., a specific rotation of [α] ο = 0 ° ± 4 ° (c = 0.500 in methanol) and the gross formula C ₂₄ H ₃₂ O ₅ . With 84% sulfuric acid, Bovogenin A gives a color reaction on the spotted plate, which runs from green, green-yellow and yellow to ocher, with the color spot taking on a pink edge.

Claims (10)

Patent claims: 1. Process for obtaining a new cardiac active substance from Boviea volubilis Harvey, thereby characterized that the plant or its parts with water or with a water-containing, extracted with water-miscible, organic solvent and the extract with lead hydroxide is treated, whereupon the extract freed from the precipitate from the organic solution Solvent freed and with a water-immiscible, organic solvent is extracted, whereupon the active ingredient is obtained in crystalline form from the organic phase will. 2. The method according to claim 1, characterized in that onions of Bowiea volubilis H. an extract prepared, the extract obtained treated with lead hydroxide, which freed from the precipitate Solution neutralized and concentrated, an ether extract is made from the concentrated solution, the ether extract evaporated and the heart-active substance in crystalline form from the residue is isolated. 3. Process according to Claims 1 and 2, characterized in that the onions are made separating the juice from Bowiea volubilis H., extracting the onion residues according to claim 1, the juice combined with the extract and the resulting liquid treated with lead hydroxide subject. 4. The method according to any one of claims 1 to 3, characterized in that one of the lead precipitation freed solution neutralized and concentrated, the concentrated solution with a chloroform-ethanol mixture extracted, the extract evaporated, the residue treated with water, the aqueous mixture extracted with ether and the heart-active substance is isolated in crystalline form from the ether extract. 5. The method according to any one of claims 1, 2 and 4, characterized in that the Ether extract after washing with soda solution and water dries and evaporates and the residue crystallized from an organic solvent. 6. The method according to claim 5, characterized in that the organic solvent is methanol, Ethanol, acetone or a mixture thereof is used. 7. The method according to any one of claims 1, 2 and 4, characterized in that the ether extract is purified by chromatography. 8. The method according to any one of claims 1, 2, 4 and 7, characterized in that the Ether extract mixed with a benzene-chloroform mixture, the mixture through an aluminum oxide column passes through, the latter washes out with a benzene-chloroform mixture and the cardiac substance with chloroform from the Alumina column eluted. 9. The method according to any one of claims 1 to 3, characterized in that as with water Miscible, organic solvent a lower aliphatic alcohol, such as. B. methanol or ethanol is used. 10. The method according to any one of claims 1 to 9, characterized in that one part or carries out all operations of this process in a nitrogen atmosphere. © 909 580/388 7.59