JPS604195A - Threitol derivative - Google Patents

Abstract

NEW MATERIAL:The compound of formula I (R is 16-18C straight-chain alkyl). EXAMPLE:1-0-Hexadecyl-2,3-di-0-acetyl-D-threitol-4-phosphorylcholine. USE:Hypotensor, blood platelet coagulant, and their intermediate. PREPARATION:The compound of formula I can be prepared by (1) reducing the compound of formula II with palladium black usually in glacial acetic acid at room temperature for 1-10hr to obtain a dihydroxylated compound, and (2) acetylating the product with e.g. acetic anhydride usually in an organic solvent, if necessary in the presence of a base (e.g. pyridine, triethylamine, etc.).

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel compound and a method for producing the same, specifically a compound represented by the general formula (wherein R represents a 016 or C18 linear argyl group) and a method for producing the same. It is.

The compounds of the present invention have antihypertensive effects and platelet aggregation activity, and are useful as pharmaceuticals or intermediates thereof.

Recently, ~1-O-
Alkyl-2-acetyl-・8n-glycerol-3-
The structure of phosphorylcholine (PAF) has been clarified, and the present inventors focused on PAF, and as a result of further research, the compound represented by the general formula [1] was found to be PAF.
The present invention has been completed based on the discovery that it has the same activity as .

In producing the compound of the present invention, the general formula (in the formula R
indicates the same meaning as above. ) is reduced to form a dihydroxy compound, and then acetylated in an organic solvent in the presence of a dibase as necessary.

Reduction is usually carried out using 4 radium black in glacial acetic acid at room temperature for 1 to 10 hours. After separating the catalyst from P, the P solution is concentrated to obtain a dihydroxy compound.

Acetic anhydride is usually used as the acetylating agent.

As the base, common bases such as pyridine and triethylamine are used. Chloroform and the like are used as the organic solvent, but the acetylating agent or base used can also be used as is as a solvent.

The reaction is allowed to proceed from room temperature to the boiling point of the solvent used for several hours after addition.

After the reaction is completed, the solvent is distilled off and purified by column chromatography to obtain the target compound.

The compound represented by the general formula [■] is produced, for example, according to the following reaction formula.

Next, the present invention will be explained in more detail with reference to Examples.

Reference Example 1 Production of 2.3-0-benzylidene-D-threitol: Under an argon stream, 2.0% was added to a suspension of 40 mg of lithium aluminum hydride in dry diethyl ether at -(capital)°C.
．． 3-0-benzylidene dimethyl-D-11 lutorate 2311qwo dissolved in diethyl ether 2-
Drop in 0 minutes. The temperature was raised to room temperature, and after stirring for 2 hours, 0.22++j of a saturated aqueous sodium sulfate solution and 5q of anhydrous potassium carbonate were added, followed by further stirring. After washing the insoluble matter with water, drying with anhydrous magnesium sulfate, the solvent is distilled off. Purify by column chromatography to obtain target product 1
Get 35 ■.

Yield 74% Optical rotation [α] + 9.19 (0 = 4
．． 86.

0HsOH) Reference example 2 1-〇-hexadecyl-2.3-0-benzylidene-D
-Production of threitol: 2.3-0-benzylidene-D-threitol 257■
was dissolved in 5 mg of DMF, and while stirring, 0.33 cm of a 22% suspension of potassium hydride in mineral oil was added at -°C, and the mixture was stirred for 15 minutes. Furthermore, 10 tons of methanesulfonic acid hexadecyhexane, 10 tons of ethanol, and 2 tons of water were added to decompose unreacted potassium hydride, and then concentrated under reduced pressure. Purify by column chromatography to obtain the product. Yield: 75% This product is a 1:1 mixture of benzylidene carbon diastereomers (high Rf component m: 9.41~
(44°C, low Rf components m, p, 53-55°C), but there is no need to separate them for subsequent reactions.

Reference example 3 1-0-hexadecyl-2,3-0-benzylidene-D
-Production of threitol-4-phosphorylcholine: 1-o-hexadecyl-2,3-0-benzylidene-D
-Threitol 730+vtJlk Dissolve in 50 ml of ether, add 660 η of triethylamine and 1.21 ml of β-bromoethylphosphoryl dichloride, and stir at room temperature for 12 hours. Then 4 m of water, )'J ethylamine 2 m
1 and heated under reflux for 2 hours. After cooling, 10 m of water was added to separate the ether layer, and the aqueous layer was further diluted with 50 m of ether for 3
After extraction, the ether layers were combined and dried over anhydrous sodium sulfate, and one portion of the solvent was distilled off.

The residue was dissolved in methanol 2- and trimethylamine 2-
and heated under reflux at 55 to 60°C for 12 hours in a sealed reaction vessel. After cooling, the mixture is concentrated, and the residue is dissolved in 90% aqueous methanol solution (30%), and 300% of silver acetate is added thereto, followed by stirring at room temperature for 2 hours. After removing the insoluble matter, it is concentrated under reduced pressure, and the residue is purified by column chromatography to obtain the desired product 583.

Yield 58% m, p, 202-205°C Example 1 -0-hexadecyl-2,3-di-0-acetyl-D
-Production of threitol-4-phosphorylcholine: 1-0-hexadecyl-2.3-0-benzylidene-D
-Threitol-4-phosphorylcholine 101W is dissolved in glacial acetic acid 5-, and radium radium is added thereto, followed by stirring at room temperature under one atmosphere of hydrogen pressure for 5 hours.

After discharging the catalyst, the solvent is distilled off under reduced pressure.

Dissolve the residue i in chloroform 5-, add 0.5 d of acetic anhydride,
Add pyridine and heat to reflux.

After cooling, add 10ml of chloroform and dilute with 10ml of water.
Wash twice with water and dry with anhydrous sodium sulfate. After distilling off the solvent, the product was purified using column chromatography to obtain white, waxy target product No. 86. Yield 86cm NMR (I
QQ MB2 0DO1,)0.88 (t, 3H
), 1.27 (s, 26H), 1.4~1.7 (m
.

2H), 2.10 (8,3H), 2.11 (Il+
, 3H), 3.22 (S.

9H), 3.25-3.44 (m, 6H), 3.9
2-4.48 (m.

□H), 5.12-5.36 (m, 2H) Patent applicant: Nippon Soda Co., Ltd. Agent Haruno Ito Yoshimi Yokoyama

Claims (2)

[Claims] (1) A compound represented by the general formula (wherein R represents Cse or a straight chain alkyl group of 01m). (2) A general formula characterized in that a compound represented by the general formula (in the formula, R represents Chs or a linear alkyl group of 018) is reduced 1 and then acetylated (in the formula, R is A method for producing a compound represented by (having the same meaning as above).