SU1397455A1 - Method of producing (2ъ-5ъ)- and (3ъ-5ъ)-diadenozinmonophosphates - Google Patents

Abstract

The invention relates to substituted heterocyclic substances, in particular the production of (2-5) and (3-5) -diadoine monophosphate (AF) used in adhology. The goal is to increase the yield of AF. It is obtained from other starting materials, M, N, 2, 3-tetrabenzo -, - iladenosine and salicylchlorophosphite, followed by treating the reaction mixture with iodine and removing the benzoyl protecting group. These conditions provide a high selectivity of the process with an improved target AF of 3-4 times. "(L

Description

co-eaten

11397455

This invention relates to an improved method for the preparation of (2-5) - and (3-5) - diadenosine monophosphate and can be used in immunopoly.

The purpose of the invention is to increase the yield of the target products.

The goal is achieved using new reagents: N

bshshoiladosine, salicyl chlorophosphite and | N-benzoyl-5-monomethoxytrntil-alenosin.

Example,

gYadenosine monophosphates (2–5 ArAi s-5 ArA).

To a solution of 50 mg (0.24 mmol) of salicyl chlorophosphite in 0.7 MP chloride mixing and cooling of ether Tethode, confirming the structure of the resulting compounds

(2-5) -Diadenosine monophosphate cneKTp, nm (24,800).

PMR spectrum (D ,, p, internal dart - tert-VION), MD: 6.85 6.60 j 6.39 singlets per 1 rt (H-2, H-8) 4.83 d (1H , H-1,

N% 2, C-tetra-yu 5, 1 Hz), 4.50d (1H, H-G, J

2.4 Hz) -, 3.83 m (1H,, J

(2-5) -i (h -5) 15

monomethoxytrityladenosine aivot 2 h at 0 С “Then in

35

mottilen at

Research institutes up to 0 ° C are added with a solution of 1 TB mg 20 (L, 17 mmol) N, N, 2,3-tetrabenzoyldenenosine in a mixture of 2 ml of methylene chloride and 0.2 p of pyridine. After 2 hours, 0.06 ml (05.72 mmol) of N-methylimidazole and 25–150 mg (0.24 mmol) of benzoyl-5– were added to the solution and the reaction was carried out. A solution of 61 mg (.0.24 mmol) iodine in 5 ml of tetra-30 1 mixture of idrofuran: water: pyridine 6: 3: 1, diluted with dilution with 30 ml of horon form,: build a 10 ml of 1% solution (potassium sulphate. Organic layer , dried with anhydrous sulfate ijiaTpHH and evaporated.

I The residue is dissolved in 25 ml of 80% ACETIC ACID, the solution is kept for 2 hours at 70 ° C and evaporated. The residue is dissolved in 30 ml of a mixture of 25% ammonia and dioxane 9: 1, kept at 70 ° C for 2 hours and evaporated. The residue after evaporation is triturated with 30 ml of ether, the ether is decanted, the powder is dissolved in water and the chromatograph is. Fired on a 100 cm column of DEAE cellulose in bicarbonate form. The column was eluted with a solution of triethylammonium bicarbonate in a concentration gradient of 0-0.05 M. The fractions containing the products were collected and evaporated in vacuo. Receive after lyophilization. (0.052 mmol), 31.8%) 2–5 APA and 800 opt. - (0.031 mmol, 18.2%) 3-5 ApA in the form of hygroscopic powder.

Spectral characteristics and comparison with notorious samples obtained by counter synthesis using 40

50

55

 5.1 Hz .p 9.0 Hz); 3.38 (1H, Н-3, Л,., 8 Hz 3.03 m (ЗН, Н-2, 3; 4) i 2.85

(1H, H-4); 2.71 m (1H, H-5) J (2H, H-5, 5) i 2.52 dd (1H, H, 13.2 Hz, J5..4 3.6 Hz). (3 -5) -Diadenosin monophosphate

 7j th,;

-Diadenosine monophosphate spectrum, 259 (25,800) ..

HMR spectrum (, internal dart-tert-Vyon), MD: 6.95, 6.75; 6.60 singlets of 1 proto each (H-2,), 4.68 d (H-1, L, 2 4.5 Hz) -, 4.56 d (1H, H-1, J 4.0 Hz) - 3.39 m (2H, H-2, 3) 3.32 dd (1H, Jj; 4.5 Hz, L 4.5 Hz) 3.24 hell (1H, H-3, L, 2 Hz ); 3.09 m (ЗН, 2НН-5); 2.91 m (1H, H-5); 2.5 (2H, H-5, 5).

Thus, the use of blunt selective benzoyl ida derivatives of adenosine and the reaction of capable salicyl chlorophosphite allows for the reaction of the first images of dinucleoside monophosphates rapidly lectually, isolating simultaneously the target product, which is 3-4 times higher than in a known manner.

Claims (1)

Formula inventions The method of obtaining (2-5) - and diadenosine monophosphates by the interaction of benzoyl-adenine production of adenosine with a derivative of triple phosphorus, followed by breakdown of the reaction mixture with iodine and protective groups, is different from the fact that, with the aim of increasing the course of the target product, N, N, 2, 3-te-zoildenenosine and N-ben are used: zoyl-5-m toxitrite, iladenosin, and salicylchlorophosphite as a trivalent derivative. structure of the obtained compounds. (2-5) -Diadenosine monophosphate, UV-cneKTp, nm (24800). PMR spectrum (D ,, p, internal standard - t-VION), MD: 6.85; 6.76; 6.60j 6.39 singlets for 1 proton (H-2, H-8) 4.83 d (1H, H-1, J ,, v  5, 1 Hz), 4.50 d (1H, NG, J  5, 1 Hz), 4.50 d (1H, NG, J 2.4 Hz) -, 3.83 m (1H,, J 1/2 2.1  5.1 Hz .p 9.0 Hz); 3.38 hell (1H, Н-3, Л,., 8 Hz) 3.03 m (ЗН, Н-2, 3; 4) i 2.85 m (1H, H-4); 2.71 m (1H, H-5) J 2.61 (2H, H-5, 5) i 2.52 dd (1H, H5, 13.2 Hz, J5..4 3.6 Hz). (3 -5) -Diadenosin monophosphate UV 7j th,; ) -Diadenosine monophosphate spectrum, 259 (25800) .. HMR-spectrum (, internal standard-ter-VION), MD: 6.95, 6.88 6.75; 6.60 singlets with 1 proton (H-2,), 4.68 d (H-1, L, 2 4.5 Hz) -, 4.56 d (1H, H-1, J,., 4, 0 Hz) - 3.39 m (2H, H-2, 3); 3.32 dd (1H, Jj; 4.5 Hz; c 4.5 Hz) 3.24 hell (1H, H-3, Lz12, 2 Hz); 3.09 m (ЗН,, Н-5); 2.91 m (1H, H-5); 2.58 m (2H, H-5, 5). Thus, the use of available selectively benzoylated derivatives of adenosine and reactive salicyl chlorophosphite allows for the first stage of the formation of dinucleoside monophosphates to be reacted quickly and selectively, simultaneously separating two target products, while the yield is increased by 3-4 times compared with the known method. Invention Formula The method of producing (2-5) - and (3 -5) - diadenosine monophosphates by reacting benzoyl derivatives of adenosine with a derivative of trivalent phosphorus, followed by treating the reaction mixture with iodine and removing protective groups, in order to increase the yield of the target product, N, N, 2, 3 -tetrabenzoyl-idenosine and N -ben are used as benzoylated adenosine derivatives: Zoyl-5-monometoxytritol, and Iladenosine, and as a derivative of trivalent phosphorosalicylchlorophosphite.