DE1467862C - Process for the production of pure gitoxin - Google Patents

Description

3 4

Propylaether-tetrahydrofuran (4: 2) / formamide) heated to reflux and then filtered off with suction. After chro-

uniform, d. H. Containing less than 1% digitoxin. Matographic examination proves the received

Instead of aluminum oxide, Gitoxin can also be practically pure from Digitoxin (less than 1%) at this point.

Silica gel for the pre-cleaning of a heavily contaminated Yield 780 g of gitoxin (32.5% of theory),

used raw gitoxins. 5.

Instead of methanol, methanol-acetone, Example 4

(1: 1), AethanoÜ ethanol-methylene chloride (1: 1), The pretreatment takes place as in Example 2. From

Methylene chloride, methylene chloride-dimethylformamide 10 g of crude product used, 8 g are

(9: 1) obtained material purified for the separation of gitoxin and digitoxin.

can be used by boiling. The best possible solution is methanol and ethanol. This product is suitable in 250 ml of ethanol / methylene. chloride 1: 1 suspended and 2 hours on the back. river heated. With the residue becomes the off example 3 boiling with 200 ml each of the same mixture

5 g raw gitoxin, 48% gitoxin and 12% digi- repeated. After vacuuming and drying

Containing toxin, in 180 ml of dimethylformamide 15 there will remain 2.1 g = 44% of theory with gitoxin

dissolved and the solution via a chromatography - a minimum content of 99% gitoxin.

column (30 cm) filled with 80 g of silica gel for chromato-. .

graphic purposes given. The column is with example 5

50 ml of dimethylformamide were washed and the After pretreatment of 4 g of crude gitoxin (with

Eluate mixed with 2.5 l of water. The precipitation 20 70% gitoxin and 20% digitoxin) accordingly

is suctioned off and with about 1 liter of water according to Example 1, the obtained 3 g of substance

to wash. After drying, 4 g of a 1 hour with 300 ml of a mixture of methylene

still colored product received. chloride-dimethylformamide 9: 1 three times for 2 hours each

The product is now boiled with 500 ml of ethanol for 1 hour. The remaining residue 1.2 g refluxed. The remaining residue, 25 = 43% of theory, is practically free of minor build-up Glycosides twice more with 200 ml of ethanol each time for 1 hour.

Claims (4)

1 2 chloroform-methanol mixture (1: 1) or with claims: methanol. The following examples show some working conditions within the scope of the invention 1. Process for the production of pure gungen. Gitoxin from the 5 B e i s ο i e 1 1 resulting crude gitoxin, characterized in that crude gitoxin is first pre-cleaned. In a first operation, K) Og pipes are cleaned is drained either by treating the in gitoxin, the 70% gitoxin and 20% digitoxin suspended crude gitoxins with activated charcoal, with 40 g fresh adsorption charcoal in 11 water or by treating the crude gitoxin solution, boiled for 1 hour, dimethylformamide together with the charcoal with aluminum oxide, and that sucks, well dried and dissolved in 11 pyridine hot, the pre-cleaned gitoxin from the remaining Then the remaining undissolved charcoal is filtered off Impurities are freed by repeatedly stirring the pyridine solution into 10 1 of water. Boil either with chloroform and a gitoxin that precipitates out of the non-glycosyl-chloroform-methanol mixture (1: 1) or with 15 dische impurities and part of the Digi-Methanol. toxins is exempt. By filtering off the aqueous 2. The method of claim 1, characterized overall pyridine residue obtained is pyrikennzeichnet with water, washed dinfrei that instead of alumina, and then dried at 110 ⁰ C. Silica gel is used. This is done in a second step. 3. The method according to claim 1, thereby purified gitoxin (80 g) once by ten times indicates that to boil out instead of the amount of chloroform and then four times with the named solvent methanol-acetone (1: 1), ten times the amount of methanol-chloroform (1: 1) 8 hours-ethanol, Ethanol-methylene chloride (1: 1), Me- den boiled under reflux. After every single ethylene chloride, Methylene chloride dimethyl form boiling the fraction remaining undissolved (in the amid (9: 1) is used. 25 gitoxin accumulates) from the solution that has gone into solution Fraction (in which digitoxin is preferably located) separated by filtration. At the paper chromatographic analysis (system: xylene-methyl- ethyl ketone (1: 1) / formamide) of 100 ^ g each 30 of the soluble fraction can be after 4. Aus The invention relates to the production of pure boiling to no longer detect digitoxin. Since in Gitoxin, which enriches digitoxin as a drug for the treatment of this fraction, proves this Weak heart serves. that the Gitoxin fraction is now also free of digi- Of the secondary glycosides, the digitalis is purotoxin. purea L., which in the usual processing of the 35 The corresponding gitoxin fraction is Accumulate drug, so far only the digitoxin has freed a kuum of chloroform residues, after which 40 g excellent importance for the treatment of pure gitoxin can be obtained. Calculated according to Acquired cardiac insufficiency. The second main gly- contained in the raw gitoxin is gitoxin Koside, gitoxin, on the other hand, was previously considered a waste product with a yield of 57%. The pure digitoxin production. This explains that 40 gitoxin is a microcrystalline powder that acts at 278 Process for a profitable isolation of the gitoxin up to 280 ° C melts and with the paper chromatography to the technical extent not previously described graphic analysis (system as above) as free of became. Two foreign glycosides have been shown for representation on a laboratory scale. Methods known. Recrystallization from Chloro- _R. . . form methanol requires large quantities of solvents According to our experience, it also delivers 4 g of raw gitoxin, 48% gitoxin and 12% digitoxin Repeated multiple times, no pure gitoxin, but containing it, are used for the purpose of separating the non- always a product containing digitoxin, as both glycoglycosidic impurities in 140 ml of dimethyl side have a strong tendency to form mixed crystals. The trenformamide dissolved. The solution is over a 13 cm tion of the two glycosides by chromatography 5 ° long chromatography column (0 = 2.3 cm) with 40 g of aluminum oxide requires due to the poor solubility Al ₂ O ₃ (acidic, activity level I) given and the check the possibility of gitoxin and its strong adhesion to the column twice with 24 ml of dimethylformamide. Al ₂ O ₃ very large amounts of solvent and suitable washed. Run-through and eluates are combined therefore only for the representation of the smallest amounts and mixed with 2 liters of water. The precipitation will of gitoxin. 55 on the suction filter and with a total of 750 ml The invention is based on the problem that washed with water. After drying the residue The crude gitoxin obtained during the digitoxin production (45 min at 120 ° C.) only gives 3.2 g of one technical scale of the slightly colored material contained therein. Mixtures, especially of vegetable dyes. The material obtained is mixed with 475 ml of methanol and get rid of digitoxin. The task is refluxed for 1 hour and the decoction solved according to the invention in that crude gitoxin with the parts that remain undissolved in the cold still next is pre-cleaned and either repeated twice by hand. The residue obtained last Treatment of the crude gitoxin suspended in water with consists of 574 mg pure after drying (see above) Activated charcoal or by treating the raw gitoxin gitoxins. Calculated according to the Solution in dimethylformamide with aluminum oxide, 65 hold the gitoxin so the yield is and that the pre-purified gitoxin from the remaining 30%. The gitoxin obtained melts at 278 to Impurities are freed by repeated 281 ° C and turns out to be with paper chromatography Boil either with chloroform and a shear analysis (separation of 100 ng in the system