DE1137742B - Process for the production of Datura alkaloids and their salts - Google Patents

Description

Process for the production of Datura alkaloids and their salts Die occurring in the various Datura species in varying mixes and quantities Active ingredients such as scopolamine, atropine, hyoscyamine, meteloidin, valeroidin and tigloidin, are known chemically and also with regard to their physiological effect.

In addition, some Datura species were occasionally still unknown Alkaloids detected without anything being known about their effects.

The invention relates to a process for the production of Datura alkaloids from a Solanaceous species, the Datura Pittieri, which has so far hardly been mentioned in the literature (Safford).

Datura Pittieri (Safford) is a shrub native to South America or small tree, also called Borrachera in Venezuela or because of the similarity its fruits with those of the cocoa tree is called "Cacafto".

The consumption of the seed of this plant effects after a stage of arousal a deep sleep.

It has now been found that Datura alkaloids, consisting of scopolamine, a new alkaloid and atropine, in the proportions Scompolamin ........................................ 76% New alkaloid ..... ................................... 23 0 / o atropine ........................................ ..... .. 1 0 / o and their Salts can be obtained if parts of the plant Datura Pittieri (Safford), especially fruits and / or leaves of this plant, with ammonia-containing chloroform or extracted with ammonia-containing methylene chloride and the extract with chloroform on a silica gel column buffered to the px value 6 Separates chromatographically into the constituents and optionally that in addition to scopolamine and atropine, the new alkaloid obtained is treated with an acid.

Preferably, the raw ammonia-containing chloroform is shaken or ammonia-containing methylene chloride extract with an aqueous acid solution from, the separated aqueous phase extracted with ammonia-containing chloroform or ammonia-containing methylene chloride and separates the extract now obtained by chromatography into the components.

The new alkaloid is more basic than scopolamine, but weaker basic than atropine.

With alkaloid precipitation reagents such as Dragendorff's reagent or Mayer's Reagent, the new alkaloid gives positive reactions, with acids they become well crystallized Salts obtained, while the active ingredient itself did not get crystallized so far could be. That Hydrobromide is obtained z. B. from absolute alcohol by adding of anhydrous ether in crystal needles arranged like a druse with a melting point 184 to 186 ° c (corrected). The picrate is obtained in the same way from alcohol and ether in rosette-like arranged yellow prisms with a melting point of 177 ° C (corrected). The elemental analysis of the picrates showed C = 50.42%, H = 4.48%, N = 18.16% and O = 34.22 O / o. From this, a molecular formula is calculated for the picrate of the new alkaloid of Cl7H2lNO5 C6H3N3O. The new alkaloid is therefore different from scopolamine (Cl7H2lNO4) by an additional oxygen atom. With the help of the melting point of the picrates and by means of paper chromatographic investigations it was possible to the identity of the new alkaloid with any of those so far in the literature The described ingredients of the examined Datura species can be excluded with certainty.

The total active ingredient content of dried fruits is on average 0.62%, that of dried leaves 0.54%.

The dried fruits or leaves are ground and first extracted in a manner known per se with petroleum ether to make fat and other lipoid soluble Remove shares.

Subsequently, the drug powder becomes exhaustive with ammoniacal Chloroform or methylene chloride extracted and the extract in vacuo under nitrogen constricted. This extract is extracted with dilute mineral acid, if necessary, the aqueous acidic solution with ammonia in a small amount Excess added and extracted with chloroform or methylene chloride. To obtain the raw bases as Dry residue, the solvent is distilled off in vacuo under nitrogen.

The separation of the raw base mixture into scopolamine, the new alkaloid and atropine is carried out by distribution chromatography z. B. on buffered silica gel, at pH 6 min chloroform as solvent. Atropine falls in the first run on, scopolamine in the next fractions, while the new alkaloid in the middle and last fractions is included.

The paper chromatographic investigation of the three active ingredients resulted in the following characteristic data: Solvent mixture .................................... .... n-butanol - glacial acetic acid - water = 4: 1: 5 method ................................ ........ increasing Steam saturation ........................................ . 15 hours running time ........................................ 14 hours paper. ... . ... Schleicher & Schüll No. 2043 a Temperature during the running time 19 to 21 ° c Spray reagent ................................... ..... Dragendorff's reagent RF value color with Migration Dragendorffs speed reagent Scopolamine ........................................ 0.56 orange red New alkaloid ....................................... 0.44 orange-red Atropine ........................................ 0.68 Orange-red None of the compounds fluoresced in UV light.

The new alkaloid is due to the effect of sleeping pills associated memory disorder used as a psychotropic drug.

Example 900g defatted drug powder made from fruits of the Datura Pittieri are filled into a glass ear (length 2 m, diameter 4.8 cm) and excluded extracted from humidity with ammonia-containing chloroform (ammonia content 4%. Then it is extracted with 101 pure chloroform and the entire extract in vacuo concentrated to 200 to 300 ml under nitrogen.

This green-brown colored solution is extracted with 5% hydrochloric acid, the aqueous acidic solution is mixed with a slight excess of ammonia and with chloroform extracted. The chloroform extract is dried with freshly calcined sodium sulfate and the solvent removed in vacuo under nitrogen. This is obtained as a dry residue 5, 58 g raw base mixture.

To separate the raw base mixture, 660 g silica gel (finely powdered, Merck) with 360 ml citric acid phosphate buffer of prr 6 (204 ml 0.1 molar citric acid solution and 156 mol of 0.5 molar disodium phosphate solution), then treated with chloroform in a glass tube (diameter 4.8 cm) slurried and compressed to a 48 cm high column.

1.0 g of raw alkaloid base mixture is dissolved in 5 mol of chloroform and applied to the column. It is then eluted with chloroform at a dropping rate of 5 to 6 drops per minute. The individual fractions are freed from the solvent in vacuo, the dry residues are weighed and examined by paper chromatography. Fraction elut quantity yield ml mg Flow I 50 1 Preroll II 30 tracks 1 160 569 2 200 53 3 20 5 4 80 13 5 21 3 6 22 3 7 95 12 8 90 5 9 90 6 10 140 8 11 90 5 12 90 7 13 140 7 14 180 5 15 250 14 16 270 22 17 600 12 18 800 20 19 700 10 20 1000 33 21 75 7 22 90 5 23 65 3 24 100 9 25 50 4 26 75 10 27 55 6 28 80 12 29 35 6 30 95 14 31 25 3 32 100 9 33 100 7 34 80 7 35 75 9 36 100 9 37 100 10 38 80 7 39 60 4 40 35 3 41 100 8 42 45 2 43 80 3 44 100 5 45 70 3 46 50 2 47 90 5 48 85 6 49 95 3 50 90 3 51 140 5 52 150 5 53 100 2 54 120 2 55 100 1 56 100 Total yield: 1012 mg The preliminary runs I and II contain atropine, fractions 1 to 19 pure scopolamine and fractions 20 to 55 the pure new alkaloid.

The yields are 760 mg of scopolamine ........................................ 760 / o 230 mg new alkaloid 23 ° / o 10 mg atropine 1 ovo For the production of the hydrobromide of the new alkaloid becomes 0.642 g of pure alkaloid in 7 to 8 ml of anhydrous chloroform dissolved and mixed with dry chloroform containing hydrogen bromide in excess, the hydrobromide settling out as a white, flaky precipitate. After removal of the solvent in vacuo under nitrogen remains a white, hygroscopic Residue. After repeated reprecipitation from absolute isopropanol and ethyl alcohol the hydrobromide is made from absolute ethyl alcohol with the addition of anhydrous ether obtained in crystal needles arranged in the form of a drusen. Melting point 184-186 ° C (corrected).

To produce the picrate of the new alkaloid, 35 mg are pure Alkaloid dissolved in 6 ml of absolute alcohol and 2 ml of saturated, alcoholic picric acid solution admitted.

It is concentrated in vacuo to 3 ml and anhydrous ether is added, until it becomes cloudy.

The picrate crystallizes in the cold as a rosette-like arrangement, yellow prisms. Melting point 177 ° C (corrected).

Claims (3)

PATENT CLAIMS: 1. Process for the production of Datura alkaloids and their salts, characterized in that parts are made in a manner known per se of the plant Datura Pittieri (Safford), especially fruits and / or leaves of these Plant, with ammonia-containing chloroform or with ammonia-containing methylene chloride extracted and the extract with chloroform on a buffered to the p-value 6 The silica gel column is separated into the constituents by chromatography and, if appropriate, also treated the new alkaloid obtained in addition to scopolamine and atropine with an acid. 2. The method according to claim 1, characterized in that the raw obtained with ammonia-containing chloroform or ammonia-containing methylene chloride Shakes the extract with an aqueous acid solution, the separated aqueous phase extracted with ammonia-containing chloroform or ammonia-containing methylene chloride and chromatographically separates the extract obtained into its constituents. Publications considered: German Patent No. 972 653; Ullmann's Encyclopedia of Technical Chemistry, 3rd edition [1953], 3rd volume, p. 202; Chemisches Zentralblatt, 1956, p. 192.