DE829595C - Process for the preparation of adenosine-5-triphosphoric acid - Google Patents

Description

Process for the preparation of adenosine-5'-triphosphoric acid The subject of this patent is a method for Animal position \ -oti f \ cletiosin-5'-triphosphoric acid, the also: \ denyll> yr @ il @ hosl @ hors; iure or: \ denosin- triphosphcrs: iurc # is called. Obesity-5'-triphosl> liors <ittre, which is a Desiring role 1> e1 of muscle contraction and other biological processes and plays clinically was used for the first time by Loh - man (Naturwiss., 17, 624, 1929) from muscle extracts isolated; her constitution became final valid as determined according to the following formula as the result of the work by Lohm on ri (1> iocliem. Z., 233, 46o, 193i; 254, 381, 1932; 282, 120, 1935) and by Lythgoe and T odd (Nature [London], 155, 695, 1945). As a result of this constitution, it can be regarded as an ester of adenosine with triphosphoric acid, in which the triphosphoric acid residue adheres to the primary hydroxyl group in the S'-position of the adenosine molecule, according to the following formula: It has been shown that when an adenositi-5'-aralkylphosphoric acid metal salt is reacted with a diaralkyl halo ester of phosphinic acid, an adenosine-5'-triaralkylpyrollohosylthoric acid results which, without actually being isolated, give adenosine-5'-pyrophosphoric acid by the action of hydrogen is split.

It has now been found that, when treating an adenosine-5'-tri-alkyl> yrophosphoric acid with a tertiary base, e.g. B. \ '---% "methylmorpholine, split off an aralkyl group and the Adenositi-5'-triaralkylpyrophosphoric acid into an Adenosi @ n-5'-diaralkylpyrophosphoric acid transforms.

It was also found that when an adenosine-5 ', diaralkylpyrophosphoric The metal salt, preferably the silver salt, is called the hydroxyl groups in the / 3- (l-Ril) ofuratiosis part of the A, denosine residue need not be protected with a diaralkyllialogen ester the phosphinic acid and .the subsequent cleavage by the action of hydrogen of the formed .'lderiosin-5'-tetraaralkyltriphosphorsäur.e, the removal of the Aralkyl groups is used, adenosine-5'-tripliophosphoric acid is formed.

Thus there is the method of manufacture according to the invention of adenosine-5'-triphosphoric acid in that an adenosine-5'-triaralkylpyrophosphoric acid 'mit a tertiary organic base is treated, the adenosine-5'-diaralkylpyrophosphoric acid formed is converted into a metal salt, this then with a Diaralkyllialogenester treated with the phosphinic acid and the resulting adenosine-5'-tetraaralkyl triphosphoric acid is cleaved by the action of hydrogen to remove the aralkyl groups.

Adenosine-5'-tribenzylpyrophosphoric acid is advantageously used as Source material. Dihenzyl ester of chlorophosphinic acid is used for aralkylation Adetiosin-5'-dibenzylpyrophosphoric acid occurring as an intermediate product is well suited.

The adenosine-5'-tetraaralkyl triphosphoric acid does not need to be isolated, but only needs to be completely freed of the impurities as far as possible with the aid of solvents before it is cleaved by the action of hydrogen. Example silver salt of adenosine-5'-di, benzylpyrophosphoric acid dibenzyl ester of chlorophosphinic acid, prepared from 49 dihenzylphosphite according to the instructions of A ther -t0n, Openshaw and Todd (Journ. Chem. SOC. 382, 1945), a solution of 5 g of adenosine-5 ' -benzylphosphorsaurem silver by Baddiley and Todd (J. Am. Chem. Soc. 648, 1947), the 12 hours at 1 ° C and io mm pressure has been dried i, in a mixture of 50 g of absolute phenol with io cc acetonitrile hei 5o ° C added. The solution is held at this temperature for 15 minutes, during which time silver chloride separates out. The mixture is then poured into 300 cc of dry ether, the precipitate which has separated out is filtered off, washed well with ether and dried for 3 hours at room temperature under 1 mm pressure. The mixture consisting of rotating adenosine-5'-tril) ertzylllN-rollliosplioräure uit, d silver chloride is now added to 40 ccm of dry Dimethvlfortnatni (1, which contain 1.5 ccm of N-methylmorpholite, and the mixture in a closed bottle for 15 minutes heated on the @ N'asserl) ad. The mixture is filtered hot in order to remove (the silver chloride, and the yellowish filtrate 11) 300 cc of dry ether is poured. The yellowish, gummy product which has separated out is washed with ether and dissolved in 100 cc of an aqueous 100% dimethylformamide solution, adding so much sodium hydroxide (3 cc normal solution) that the solution reacts neutrally. Aqueous silver nitrate solution (5 g in zoo ccni water) is added to the filtered solution. After 2 hours, the precipitated silver salt of adenosine-5'-dibenzvlllvropliosphoric acid is separated off in an amount of 6.2 g, washed well with water and acetone and dried for 12 hours at 60 ° C. and 1 mm pressure. Adenosine - @ '- tril> phosphoric acid To a 50 ° C solution of (ig of the above-described silver salt of: 1 (leiiositi-5' - (til) enzylpyrophosphoric acid in a mixture of 50 g of absolute phenol with 1o ccn of acetonitrile is dibenz_vIester der added Chlorhhosphinsäure and iMischung 15: minutes kept at 5o ° C and poured in in 300 cc of dry ether, the precipitated precipitate is filtered off, washed well with ether, and Z hours dried at Zimniertetilperatur under reduced pressure 200 CCM 5oo / oiges.. Aqueous dioxane are added, undissolved silver chloride is removed by centrifugation, and the clear solution is hydrogenated at room temperature under normal pressure with a mixture of palladium oxide and palladium-carbon catalysts the catalyst was removed by filtration and barium oxide was added to the strongly acidic filtrate gt until the pH is adjusted to 6. The barium salt which has precipitated is separated off by centrifugation, washed twice with cold water, redissolved in approximately 17o ccm of cold VI n hydrochloric acid, centrifuged to remove the undissolved matter and the barium salt by adding two parts by volume of 95o / oigem Ätliatiol precipitated again. The separated salt is redissolved in 2 ounces of cold 1 / 2on hydrochloric acid, the solution is centrifuged and 2oo% aqueous barium acetate is added to adjust the pH to 4.6. The separated crude barium salt of adenosine-5'-triphosphoric acid is separated off by centrifugation, washed successively with water, 500% ethanol, 95% ethanol and ether and dried at room temperature under reduced pressure. The yield is 2 g.

The crude barium salt is made up of some barium pyrophosphate and barium adenosine 5'-pyrophosphate contaminated. These impurities can be caused by the reprecipitation of the barium salt pH = .4 to remove the adenosine-5'-pyrophosphoric acid and convert it to the acridine salt and recrystallization from water to remove the pyrophosphate be eliminated. This creates pure Adeiiosin-5'-tril> phosphoric acid, which is beneficial is isolated either as the barium salt or as the acridine salt (read from water in yellow Needles crystallize and lyei melts about 28 ° C; it is identical to one Sample that melts at 218 ° C and is derived from muscles and fully biological Has effectiveness.

Claims (2)

PATENT CLAIMS: 1. Process for the production of adenosine-5'-triphosphoric acid, characterized in that an adenosine-5'-triaralkylpyrophosphoric acid is used treated with a tertiary organic base, the adenosine-5'-diaralkylpyrophosphoric acid formed Converted into a metal salt, this metal salt with a diaralkyl halogen ester of Treated phosphinic acid and the resulting adenos, in-5'-tetraaralkyltriphosphoric acid cleaves to remove the aralkyl groups by the action of hydrogen. 2. Procedure according to claim 1, characterized in that the adenosine-5'-tetraaralkyl triphosphoric acid not isolated, but before cleavage by the action of hydrogen with the help of Solvents is only freed from impurities as far as possible.