SU740740A1 - Method of preparing monophosphoinositide ammonium salt - Google Patents

Description

nopyranose, which is then condensed with a phosphatidyl acid of the formula (IU

,, about//

I II SN.OR-OH

he

in pyridine in the presence of 2,4,6-triiEopropylbenzenesulfonyl chloride, followed by the removal of the protective groups of the obtained monophosphoinositide derivative by boiling with 80% acetic acid. .

i PRI me R. 1/3 /, 2: 5, b / 4-di-0-cyclohexylidene-Sn-myo-inositol.

A mixture of 25.00 g of myo-inositol in 250 m of cyclohexanone and 65 ml of benzene is heated in the presence of H-toluenesulfacid with a water separator DinaCitapKa. After separating 8 ml of water, the reaction mixture was filtered, the filter was washed with 1.5 N, ammonia solution (34x50), 0.25 g of sodium carbonate was added and the mixture was distilled with steam, the remainder of the water was removed with benasl. (2: 4/6/5 1/3), 2: 3/1/4/6 / and 1/3 /, 2: 5.6 / 4 / - myo-inositol-kinetics, which grow in 100 ml carbon tetrachloride and left to crystallize. The precipitate is separated, the uterine paicTBOp is evaporated, the residue is dissolved in chloroform and chromatographed on a column with alumina of the second degree of activity. The chloroform ethyl alcohol (1: 1) system washes out the mixture of the remaining inositol diketals, which is rechromatographed on a column of silica gel, eluting with 1/3 /, 2 5,6 / 4 / -di-0-cyclohexylidene Sn-myo-inositol (a) with the chloroform acetone (94: 6). After crystallization from a mixture of benzene-petroleum ether (70-100 ° C, 2: 3). 8.45 g (18.1%) of ACT are obtained, mp. 132 133 ° C, - 0.36 (silica gel, benzene acetone, 7: 3).

3, 4,6-Three-0-acetyl-1,2-0- (2, 3: 4, 5-di-O-cyclohexylidene-H-myo-inositol-6-ortho-acetyl) - | b - D - mannopyranose. .

A solution of 0.475 g of diketal A and 1.05 g, 3, 4, 6-tri-0-acetyl-1, 2-ethyl-ortho-acetyl-b - and -mannopyranose in 15 ml of dichloroethane is boiled in a Yoxlet apparatus loaded with 2 g of molecular sieves Type 4A, 10-15 min. Then, 0.0103 g of M-toluenesulfonic acid is introduced into the reaction mixture and the mixture is kept under reflux for 3.5 hours under the same conditions. After completion of the reaction, a few drops of pyridine are added and evaporated. The residue (1.5 g) was separated by preparative chromatography on alumina of the II degree of activity in the chloroform-acetone system (9: 1). From the fraction CRE-0.27, 0.206 g (24.6%) of 3.4, 3'-tri-0-acetyl-1, 2-0- / 2,3: 4,5-di-O-cyclohexylidene- Svi-myo-inositol-6-orthoacetyl / -p-D-mannopyranose (B) with t. Il. 172-174 ° С (from zfir), + 2.0 ° С (s-0.5, chloroform).

1-0- (1,2-Di-0-stearoyl-511-glyceryl-3-0-phosphoryl) -2,3,: 4,5-di-O-cyclohexylidene-6- (3,4, 6- tri-O-acetyl-P-T) -mannopyranosyl-1,2-orthoacetyl) -Sn-myo-inositol.

A solution of 0.62 g of 2,4,6-triisopropylbenzenesulfonyl chloride, 0.91 g of orthoester B in 10 ml of pyridine is stirred for 30 minutes at 18-20 C. Then

0.48 g of 1,2-di-O-stearoyl-5n-glycerol-3-0-pforphan acid is added. M.p. 67-68 ° C, Go (. 4.5 ° Heated for 1 minute at 60 ° C until complete dissolution and continue stirring

0 12 hours at 18-20 ° С. After that, 17 ml of chloroform is added to the reaction mass and stirred for 1.5 hours. At the end of this period, 5 ml of water are poured, stirring the mixture for 10 minutes.

5 The solvents are distilled off, the residue is separated by chromatography on silica gel, eluting with protected phosphatidylinositol with a mixture of chloroform and methyl alcohol (97: 3). After

0 1 By evaporation of the solvent and crystallization from acetone, 0.54 g (60.6%) of 1-0- (1,2-di-0-resteroyl-Srt-glyceryl-3-O-Phosphoryl) -2.3: 4 is obtained, 5-di-O-cyclohexylidene-6- (3,4,6-tri5-0-acetyl- | b-U-mannopyranosyl-1,2-ortho-acetyl) -5n-mycoinosite (G) with mp. 38-49, °, W 6.57:, m4-12,48 °,

td & 13.14 °, 15.77 ° (c-оТ35, chloroform). Tt.f —O, 39 (benzene-acetone, 7: 3) .i

Found,%: C 61.65; H 8.43; P 2.86.

Si

Calculated: C 62.06; H 8.96; P 3.01.

Ammonium salt of 1-0- / 1,2-di-0-stearoyl-SM-glyceryl-3-O-phosphoryl-Sn-myo-inositol.

A solution of 0.19 g of protected monophosphoinositide G in 15 ml, 80%

aqueous solution of acetic acid is heated under stirring for 4 hours. The solvents are evaporated, 3 MP of a mixture of alcohol and chloroform (3: 1) are added to the residue, 4 N aqueous is added.

ammonia solution to pH 8.0. After removal of the solvents, the phosphatidyl nositol ammonium salt is re-precipitated with 5 MP of acetone from 1 ml of chloroform. Yield 0.06 g (47.6%). m.p. 18Q-182 ° C (dec,). 7.1,

, + 7.4, 17.8.6 (3, V, 22.3, 23.2 Gs-0.25, chloroform-methyl alcohol, 4 N. Md.OH, 9: 7: 2).

Found,%; C, 60.81; H 11.08; N 1.47; P 3.36,

Claims (1)

C, sN9cP g P "ъzGrT g; - The formula of the invention for the ammonium salt of monophosphoinositide of the general formula OH OH) -f-0-CH ,, o HO-OOOG H. 1:) and - t I n and er CHaOOOQj Hjs based on myo-inositol, in order to simplify the process, the initial myo-inositol is treated with cyclohexanone in the presence of p-toluenesulphonic acid, obtained by 1/3 /, 2; 5, b / 4 / -di-0-cyclohexylidene-Sti-myo-inositum is reacted with 1, 2-ethyl-ortho-acetyl-p) - D-mannopyranose in dichloroethane solution in the presence of n-tolu-6-sulfyl acids with the formation of 3,4, bg-tri0-O-acetyl-1,2-0 - (2,3: 4,5-di-O-cyclohexylidene-511-mioi ozit-b-o-adetil) - | L- © -mannopiranoey, which is then condensed with a phosphatidic acid of formula (11). P lH gCOOCH p F CHiOP-OH in pyridine in the presence of 2,4,6-triisopropylbenzenesulfonyl chloride, followed by removal of the protective groups of the resulting monophosphoinosinitide derivative by boiling with 80% acetic acid. Sources of information taken into account in the examination, 1. Lyutik A.I., Salovnikova MS, Shvets V, I., Evstigneeva R.P. Research in the field of asymmetrically substituted myo-inositol derivatives. XII, Synthesis of mono - and diphosphoinositides. JOH, 44, 2573 (1974) prototype.