SU478008A1 - Method for preparing adenosine 21,31-cyclophosphate - Google Patents

Description

The invention relates to methods for ;; Adenosine-2, 3-cyclophosphate, which is used in biochemical and medical research.

A known method of producing adenosin-2,

3 -sislofosfa-by cyclization of adenosine-2, 3-cyclophosphate using as a cyclizing agent ethyl or benzyl chlorogolic acid in a methanol-acetone medium in the presence of bases. The yield of the target product is 72%.

In order to increase the yield of the target product, it is proposed to carry out the cyclization of adenosine-21,3- or 2 (3) -monophosphoric acids with chloroic acid esters in dimethylformamide, using

triethylamine as base.

Dimethylformamide in the presence of triethylamine provides horreye dissolution of adenosine monophosphates and the rapid progress of the reaction of ciphizacin. The triethylammonium salt of adenosine-2, 3 n-chlorophosphate formed during the reaction under the conditions of the reaction is poorly soluble in dimethylformamide and precipitates. This difference in the solubility of the triethylammonium salts of adenosine monophosphate and cyclophosphate provides selective precipitation from the reaction mixture only pure adenosine-2, 3 -i-cyclophosphate and contributes to the completion of the reactivity. Application tripropil- instead of triethylamine, tributyl amine and other higher yields eastor propelling dimethylformamide cojm cyclophosphate adenosine and depositing them from reakschyunnoy droiskhodat mixture together with unreacted adenosine salts that snizhaech- yield and purity of the target P1yud) CTA. Trimethylamine does not provide dissolution of the initial substance in dimethylformamide.

Example 1. To O, 7O g (2 mmol) of adenosine-2'-monophosphoric acid, 8 ml of dimethylformamide and 1.4 ml (ip mmol) of triethylamine are obtained. About 31 ml (4 mmol) of 1-methyl chloride of chlorogolic acid, j are introduced into the clear solution.

The mixture was stirred at room temperature for 1 hour, then 0.31 ml of chlorogolic acid methyl ester was added again and stirring was continued for 0.5 hour. Inserted precipitate is filtered and washed with ether.

Get O, 79 g of the triethylammonium salt adenosine-2 (3) -cyclophosphate (91% of theoretical) .i

Chromatography product is homogeneous in various solvent systems for paper and thin layer chromatography. In the solvent system isopropanol:

RjO, 52.

1% (N H)

S Oh, (2: 1)

Chromatography was performed on dhsh / chromatography and electrophoresis paper of the Leningrad1 S. brand paper mill.

Example 2 In 1, O5 g (2.5 mmol of adenosine-2 (3) -monophosphoric acid, 11 ml of dimethylformamide and 2 ml (14 mmol) of triethylamine are added. About 46 ml (bmmonium) of methyl ester are added to the plant) Chloroic acid. The mixture is stirred for 1.5 hours at room temperature, then another 0.31 ml of methyl chloroforic acid ester is added / shucked and the mixture is stirred for 0.5 hours. The precipitate formed is filtered and washed with ether.

Receive 1.21 g of triethylammonium salt adenosine-23-cyclophosphate (93% of theoretical).

Chromium product is atographically homogeneous, And f 0,52 in cncTOt / e solvents iso

(NH)

0 (2: 1)

prupanol:

Subject invention

The method of obtaining adenosine-2, 3 I-shshlofosfat by cyclization of ad ((aosno-4

-2v, 3i or. 2 (3) -monophosphoric acids by chloroforic acid esters in an organic solvent in the presence of bases, followed by isolation of the target product by known methods, characterized in that, in order to increase the yield of the desired product, dimethylformamide is used as the organic solvent and triethylamine is used as the base .