JPH0453493A - Production of phosphoric ester - Google Patents

Abstract

PURPOSE:To efficiently produce the subject ester having an excellent surface-active effect, low in skin irritation and excellent in biodegradability by reacting a phosphoric ester with a polyvalent alcohol in the presence of a specified phospholipase D. CONSTITUTION:A compound of formula I [R is 8-32C (un)saturated hydrocarbon; A is organic residue obtained by removing one OH from 1-6C primary hydroxyl group-containing base; M is H, alkali (alkaline earth) metal, ammonium, etc.] is reacted with a compound of HO-X-OH [X is residue obtained by removing two OH group from one of compound (i)-(iv). (i) mono or polyether of OH-(YO)m- H (m is 2-50. Y is 2-4C alkylene or substituted alkyl) (ii) polyglycerin of 2-50 condensation degree (iii) 4-7C mono(di)saccharide having two or more primary alcohol group in molecule (iv) 3-7C sugar alcohol] in the presence of phospholipase D capable of inducing transformation reaction between a phospholipid an a primary alcohol, thus obtaining the objective ester of formula III.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a method for producing a phosphoric acid ester, and more specifically, it has excellent surfactant ability, emulsifying ability, and ribbon forming ability,
The present invention also relates to a method for producing a phosphoric acid ester that has low skin irritation and good biodegradability.

[Prior Art and Problems to be Solved by the Invention] Phosphoric acid esters are used in a wide range of fields such as detergents, textile treatment agents, emulsifiers, rust preventives, liquid ion exchangers, and pharmaceuticals. In recent years, especially in the case of cleaning agents, there has been a tendency to desire detergents with low irritation properties, so phosphoric acid monoester salts and the like have come to be widely used.

On the other hand, since various phospholipids having a phosphate ester structure, including lecithin, are constituents of cell membranes,
It is expected to be hypoallergenic and biodegradable.
Alternatively, many phosphoric acid ester derivatives having structures similar to phospholipids have been synthesized by chemical synthesis or the like. but,
These phosphoric acid ester derivatives did not have sufficient surface activity, skin irritation, etc. Most of these conventional phosphoric acid ester derivatives are compounds having one phosphoryl group, and the physical properties and simple manufacturing methods of compounds having two phosphoryl groups are hardly known. That is, U.S. Patent No. 4.22
Only a few compounds were known in No. 0.611.

However, the method for producing this compound having two phosphoryl groups has been complicated by chemical synthesis, has many by-products, and has a low yield.

Under these circumstances, there has been a desire to develop an efficient method for producing phosphoric acid esters that have excellent surfactant properties, are hypoallergenic, and have good biodegradability.

[Means to solve the problem]

Therefore, the present inventors conducted extensive studies to solve the above problems, and found that by using phospholipase D, high purity and high yield can be obtained using the following general formula ( It was discovered that a phosphoric acid ester represented by I) could be obtained, and the present invention was completed.

The present invention is shown by the following reaction formula.

Margin below OM(II) (II[>R-0-P-0
-X-0-P-0-R(I)OM OM [In the formula, R represents a saturated or unsaturated straight chain or branched hydrocarbon group having 8 to 32 carbon atoms, and A represents a saturated or unsaturated straight chain or branched hydrocarbon group having 1 to 32 carbon atoms. Represents an organic residue obtained by removing one hydroxyl group from the primary hydroxyl group-containing base of 6, M represents a hydrogen atom, an alkali metal, an alkaline earth metal, ammonium, alkylammonium or haalkanol ammonium, and X represents the following ( (1) 110-CY-0)=-H (where m is 2 to
5o integer, Y represents an alkyl group or substituted alkyl group having 2 to 4 carbon atoms) (2) Polyglycerin with a degree of condensation of 2 to 50 monosaccharides or trisaccharides having 2 or more carbon atoms and having 2 or more carbon atoms (4) sugar alcohols having 3 to 7 carbon atoms; ■)
A phosphoric acid ester (I) having two postboryl groups, which is characterized in that it is reacted in the presence of phospholipase D that causes a transfer reaction between a phospholipid and a primary alcohol.
This is a manufacturing method. The term "posboryl group" as used in the present invention means a phosphoryl group to which a saturated or unsaturated straight or branched hydrocarbon group having 8 to 32 carbon atoms is bonded.

In the above general formula (I [) representing the raw material phosphate ester, the alkyl group or alkenyl group represented by R is, for example, hexyl, octyl, decyl, dodecyl, tetradecyl, hexadecyl, octadecyl, eicosyl, tocosyl, tetradecyl, hexadecyl. , oftacocil, doriacontyl, todoriacontyl, 2-ethylhexyl,
2-hexyldecyl, 2-octyldodecyl, 2-decyltetradecyl, 2-dodecylhexadecyl, 2-tetradecyloctadecyl, methyl-branched instearyl, oleyl, octagenyl, decadienyl, tetradecadienyl , hexadecagenyl, octadecagenyl, eicosagenyl, docosagenyl, tetracosagenyl, hexacosagenyl, octacosagenyl, triacontagenyl, dotriacontagenyl, hexacosagenyl, oftadetrienyl, eicosagenil, docosagenil, tetracosagenil,
Hexacosagenyl, octacosagenyl, tricontatrienyl, dotricontatrienil, eicosate F
Laenyl, docosatetraenyl, tetracosatetraenyl, hexacosatetraenyl, octacosatetraenyl, triacontatetraenyl, dotriacontatetraenyl, tocosapentaenyl, tetracosatetraenyl,
Hexacosatetraenyl, octacosatetraenyl, triacontatetraenyl, dotriafuntapentaenyl, docosahexaeni Jlz.

Examples include tetracosahexaenyl, hexacosahexaenyl, octacosahexaenyl, doriacontahexaenyl, dotriacontahexaenyl, and the like. Also, hydrogen atoms, alkali metals, alkaline earth metals, ammonium,
Examples of M which is alkylammonium or alkanol ammonium include potassium, lithium, sodium, beryllium, magnesium, calcium, strontium, barium, ammonium, trieta)-JL
/ammonium, trimethylammonium, triethylammonium, etc.

Examples of such raw material phosphate esters include phosphorylcholine derivatives, phosphorylethanolamine derivatives, phosphorylglycerol derivatives, and JP-A-62-149690.
Examples include phosphoric acid ester derivatives having a quaternary ammonium salt in the same molecule as disclosed in No.

In addition, in the compound described in (1), which is the other raw material, Y is an alkylene group having 2 to 4 carbon atoms which may have a substituent, such as ethylene, propylene, butylene,
-Methylpropylene, etc., and m is an integer of 2 to 50, preferably 4 to 50, particularly 4 to 20. Particularly preferable examples include polyethylene glycol with an average molecular weight of 200 (hereinafter referred to as PEG 200) and polyethylene glycol with an average molecular weight of 400 (hereinafter referred to as PEG 200).
400), polyethylene glycol with an average molecular weight of 600 (hereinafter referred to as PEG 600), an average molecular weight of 75
Polyethylene glycol with an average molecular weight of 0 (hereinafter referred to as PIEG 750), polyethylene glycol with an average molecular weight of 1000 (hereinafter referred to as PBG 1000), polypropylene glycol with an average molecular weight of 200 (hereinafter referred to as PPG200)
etc.

In the polyglycerin described in (2), the degree of condensation of polyglycerin is 2 to 50, but 4 to 50, especially 4 to 50.
20 is preferred. Particularly preferred polyglycerin is, for example, polyglycerin with an average molecular weight of 500 (hereinafter referred to as PG
500), polyglycerin with an average molecular weight of 750 (hereinafter referred to as PG 750), and the like. Examples of monosaccharides used in the present invention include xylulose, ribulose, fructose, sorbose, psicose, tagatose, sedoheptulose, glucoheptulose, and mannoheptulose, and examples of disaccharides include sucrose and maltose. , cellobiose, trehalose, lactose, etc.

Further, examples of the sugar alcohol described in (4) include hacrycerol, erythritol, ribitonil, arabitol, xylitol, sorbitol, mannitol, galactitol, sedoheptulose, and verceitol.

Examples of phospholipase D include phospholipase D1 that causes a transfer reaction between phospholipids and primary alcohols, particularly phospholipase D (lE
(:, 3.1.4.4) is preferred. The origin of phospholipase D is not particularly limited, but for example, phospholipase D produced by a microorganism of the genus Nocardiopsis (see Japanese Patent Publication No. 63,62195), phospholipase D produced by a microorganism of the genus Actinomadeula (Japanese Patent Publication No. 1-176)
75), phospholipase D produced by a microorganism of the genus Streptomyces (see Japanese Patent Publication No. 1-12474 and Japanese Patent Application Laid-open No. 219373-1983), phospholipase D produced by a microorganism of the genus Kitasatosporia (see Japanese Patent Publication No. 64-80285).

Phospholipase D produced by these microorganisms is
It can be used in the form of live bacterial cells, dried products thereof, crushed products thereof, or in the form of crude enzymes or purified enzymes obtained by separating or purifying them, and if necessary, they can be photocured. It can also be used in the form of entrapping immobilization in polyurethane resin, urethane prepolymer, K-carrageenan, etc.

To carry out the present invention, raw material phosphate ester (II) and polyhydric alcohol (I [I
) in the presence of the phospholipase D to cause a phosphoryl group transfer reaction.

Examples of the solvent used include a mixed solvent of an organic solvent such as ether, benzene, dichloromethane, and chloroform, and a suitable aqueous solvent. Suitable additives that promote the action of phospholipase D or help stabilize the enzyme can be added to the aqueous solvent. Examples include proteins such as albumin and casein, buffers such as acetic acid, citric acid, and phosphoric acid, and neutral salts such as calcium chloride.

The reaction molar ratio, the amount of phospholipase D used, the amount of solvent used, etc. can be selected as appropriate. For example, the reaction molar ratio is usually about 0.1 to 100 times the polyhydric alcohol, preferably 0.1 to 1 mole of the raw material phosphate ester (■).
It is preferable to use up to 10 times the molar amount. The amount of phospholipase D used is about 10 to 100,000 units, preferably about 100 to 500 units, per Ig of raw material phosphate ester (II).
An example is 0 units. Furthermore, the amount of solvent to be used is approximately 2 to 1 with respect to the raw material phosphate ester (I[).
For example, about 00 times.

Although the reaction temperature and reaction time can be selected as appropriate, preferred examples include about 20 to 80°C and about 1 to 240 hours.

In addition, during the above reaction, together with the silicic acid ester represented by the general formula (I), the general formula (IV) R-0-P-0-X
A monophosphoric acid ester represented by -OH(TV)0M (wherein R, M and X have the same meanings as above) is mixed and produced as an intermediate. These reaction mixture products are separated from the reaction system by means such as organic solvent extraction, and the substrate phosphate ester (II
) by adding 0.5 to 1.5 mol, preferably 0.7 to 1.3 mol, and adding phospholipase D again to carry out the reaction repeatedly, the desired silicic acid ester (1) can be obtained at a high concentration. Obtainable.

The phosphoric acid ester (I) produced as described above can be separated and recovered from the reaction system, for example, by extraction treatment with an organic solvent, and if necessary, further solvent fractionation, silica gel chromatography, high performance liquid chromatography,
Although it can be purified using an appropriate method such as centrifugal liquid-liquid partition chromatography, it can be purified without separation and purification.
It can also be used as is for various purposes.

〔Example〕

Hereinafter, the present invention will be explained with reference to Examples.

Example 1 (i) 50 g of 2-(hexyl)decyl phosphoric acid is placed in a reactor, 155 g of IN potassium hydroxide aqueous solution is added, and the temperature is raised to 60° C. while stirring.

A solution prepared by dissolving 117 g of IJ methylammonium chloride in 63 g of water was added dropwise, and the mixture was allowed to react at 60° C. for 5 hours. After the reaction is complete, filter
After the reaction solution was purified by passing it through an electrodialyzer, water was distilled off to obtain 23 g of 2-(hexyl)decyl phosphate having a 2-hydroxy-3-trimethylaminopropyl group in the same molecule.

Below margin (')Ij-((')12) 6-CH2(ii)(i
), 60 g of PEG 400 (polyethylene glycol 400 manufactured by Wako Pure Chemical Industries, Ltd.), 110 g of NaC, 75,000 phospholipase DM, and 150 ml of water! was added and reacted at 37°C for 7 days with shaking.

After the reaction was completed, chloroform and methanol were added and extracted to obtain an organic layer, which was concentrated and dried. Further purification was performed by silica gel chromatography to obtain 2.7 g of diphosphoryl PEG 400, which was the target product.

The resulting diphosphoryl PB0400 having a 2-(hexyl)decyl group was subjected to NMR and elemental analysis to confirm its structure.

The data is shown below.

'H-NMR [270MHz manufactured by JEOL Ltd.; CDCl
3. TMS standard δ (ppm)] 0.9 (t, 12H, a), 1.3 (bs, 4g)
1. b).

1,5 (bs, 2H,c), 3.7 (m,
44H, d).

4,0 (m, 48.e) Elemental analysis of the following margin: Calculated value as C5JzoPiO+aNaz C: 56.13%, H: 9.60%, P: 5.4
% measurement value C: 55.78%, H: 9.53%, P:
5.2% Example 2 15 g of a phosphoric acid ester having a 2-hydroxy-3-trimethylaminopropyl group in the same molecule, synthesized from 2-(tetradecyl)octadecyl phosphoric acid by the same method as in Example 1 (i) ), Example 1
400117) Bill 1. Using 80 g of mPG 750 (polyglycerin #750 manufactured by Hanhon Yakuhin Co., Ltd.), the same operation as in Example 1 (ii) was carried out to obtain diposilyl PG 7 having a 2-(tetradecyl)octadecyl group.
502. Ig was obtained.

The following margin [1, H, (CH2) = CH2 CH2 (CH2) , , CH3 CH3 (CH2), 3CHOOell (CH2), 3C
)I31 II CIt, -Q-P-0(C3H6(12), Q-P
-0-CIt2 elemental analysis: CsJ+5oP2L7Na
Calculated value as s C: 60.68%, H: 10.29
%, P: 3.3% measured value C: 60.21%, lI
: 10.06%, P: 3.1% Example 3 Using 15 g of n-)decylphosphorylcholine as the raw material phosphoric acid ester, P instead of PE6400 in Example 1.
EG 600 (polyethylene glycol 6 manufactured by Wako Pure Chemical Industries, Ltd.
00) Using 45 g, the same operation as in Example 1(u) was carried out to obtain diphosphoryl PB having an n-dodecyl group.
6600 1.5g was obtained.

Margin elemental analysis below: Calculated values as C5JrosPzL1Na2 C: 53.14%, H: 9.09%, P: 5.3%
Measured value C: 52.77%, lI: 8.91%, P
:5.2% Example 4 Oleylphosphorylcholine 1 as raw material phosphate ester
5g of PE in place of PEG 400 in Example 1.
6200 (Polyethylene glycol 200 manufactured by Wako Pure Chemical Industries)
Using 30 g, the same operation as in Example 1 (u) was carried out to obtain diphosphoryl PE6200 having an oleyl group.
1.8g was obtained.

Margin below

Claims (1)

[Claims] 1. General formula (II) ▲ Numerical formulas, chemical formulas, tables, etc. are included ▼ (II) [In the formula, R is a saturated or unsaturated linear or branched carbonized carbon having 8 to 32 carbon atoms. Represents a hydrogen group, A represents an organic residue obtained by removing one hydroxyl group from a primary hydroxyl group-containing base having 1 to 6 carbon atoms, and M represents a hydrogen atom, an alkali metal, an alkaline earth metal, ammonium, alkylammonium, or an alkanol. Ammonium] A compound represented by the general formula (III) HO-X-OH (III) [In the formula, X is a residue obtained by removing two hydroxyl groups from any of the following compounds (1) to (4) (1) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (where m is an integer of 2 to 50, Y is an alkylene group or substituted alkyl group having 2 to 4 carbon atoms) Mono or polyether represented by (2) Polyglycerin with a degree of condensation of 2 to 50 (3) Monosaccharides or disaccharides with 4 to 7 carbon atoms having two or more primary alcohol groups in the molecule (4) Sugar alcohols with 3 to 7 carbon atoms] General formula (I) characterized by reacting the compound represented by in the presence of phospholipase D that causes a transfer reaction between phospholipids and primary alcohols ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I) A method for producing a phosphoric acid ester represented by the formula [wherein R, X and M have the same meanings as above].