CS202484B1 - Method of evolving basis of alkaloids ergotoxine type from their salts - Google Patents

Description

The present invention relates to a novel process for the isolation of ergotoxin-type alkaloids (ergocristin, ergocornin, ergocryptine 10 and jb) from their mineral acid-editing salts. The process makes it possible to obtain from these salts more easily and in a higher yield than the above-mentioned substances and any mixtures thereof, as well as to decompose salts of hydrogenated alkaloids of this type.

Alkaloids of the ergotoxin type are obtained from natural raw materials for the preparation of pharmaceutical preparations. Their insulation is costly and time consuming. Therefore, simplifying one of the production steps associated with an increase in yield represents a significant economic benefit. The prior art processes for solving these compounds have solved the problem of decomposing their salts as follows: the salt was mixed together with an appropriate amount of sodium bicarbonate in aqueous ammonia solution. The resulting aqueous suspension was then extracted with suitable organic solvents.

The combined organics were then shaken with water, concentrated to an appropriate volume, and filtered through a pad of alumina. The filtrate was then evaporated to dryness. During the multiple extraction, there was necessarily a loss of raw material by entraining part of the organic phase into the aqueous layer - these losses are small in percentage, but due to the high cost of the processed raw material, they are not negligible. Erotoxin-type alkaloids are readily epimerized in solution, the dextrorotatory enantiomers formed are less pharmacologically active and are unwanted ballast in the raw material. Due to the considerable time required for repeated extraction up to 202 484

202,484 there is a marked increase in the content of the described worthless isomers in the feedstock.

These disadvantages are overcome by the process of the present invention. The alkaloid addition salt with the appropriate mineral acid is decomposed at room temperature with gaseous ammonia in ethanol, methanol, acetone, ethyl acetate, benzene or ether, preferably chloroform, the insoluble ammonium salt is separated from the alkaloid base solution by filtration, the excess ammonia is expelled by heating. The method of liberating alkaloid bases from their salts can be used to decompose any acid addition of alkaloid salts. The condition is the insolubility of the ammonium salt of the acid and, conversely, the solubility of the alkaloid base in the solvent. The method is also applicable to decomposition of salts of hydrogenated alkaloids (9,10-dihydro-D-lysergic acid derivatives).

Example 1 g of crude ergocristinium hydrogen phosphate was stirred at room temperature in 80 ml of chloroform. After about 5 minutes of introduction of ammonia gas, the mixture was heated to boiling. After expulsion of the excess ammonia, the mixture was cooled, the ammonium phosphate was filtered off, the filtrate was purified by passing through a layer of alumina and evaporated to dryness.

Example 2 g of a crude mixture of ergocorninium hydrophosphate and ergocryptinium was stirred in 70 ml of ethyl acetate and ammonia gas was introduced. After expulsion of the excess ammonia, the mixture was cooled, filtered through a pad of diatomaceous earth, the filtrate was purified by passing through a pad of alumina and concentrated. The precipitated crystalline base was filtered off and washed with cold ethyl acetate.

Example 3 g of dihydroergotoxinium methanesulfonate was stirred at room temperature in 50 ml of chloroform. After about 5 minutes of introduction of ammonia gas, the mixture was heated to boiling. After expulsion of the excess ammonia, the mixture was cooled, the ammonium methanesulfonate was filtered off and the filtrate was evaporated to dryness.

Claims (1)

BEFORE THE INVENTION A process for the release of ergotoxin-type alkaloids or hydrogenated ergotoxin-type alkaloids from their salts, characterized in that the alkaloid salt with the respective mineral acid is decomposed at room temperature with gaseous ammonia in an environment of ethanol, methanol, acetone, ethyl acetate, benzene or ether; preferably chloroform, the insoluble ammonium salt is separated from the alkaloid base solution by filtration, excess ammonia is expelled by heating, the solution is purified by chromatography on an alumina column and evaporated to dryness.