KR0162283B1 - Nonionic vitamine-e derivatives and their preparation method - Google Patents

Abstract

The present invention relates to a nonionic vitamin E derivative capable of forming an amphiphilic polymer vesicle and a method for preparing the same. More specifically, the nonionic compound represented by the following Chemical Formula 1 can form an amphiphilic polymer vesicle having an antioxidant action that improves thermodynamic stability and excellent in vivo compatibility and protects living cells from harmful free radicals. Vitamin E or polyethoxylated vitamin E derivatives and methods for their preparation, and amphipathic polymer vesicles obtained therefrom:

[Formula 1]

Wherein n is 0 An integer of 50; A is -CH ₂ -CH (CH ₃ )-or CH = C (CH ₃ )-; B is CH ₃ bonded to at least one of 5-, 7- and 8- positions; m is 1 An integer of 3; R is an acrylic acid derivative, methacrylic acid derivative or crotonic acid derivative represented by the following formula (2).

Description

Nonionic Vitamin E Derivatives and Methods for Making the Same, and Amphiphilic Polymer Baccicles Having Antioxidant Activity Formed Using the Same

In Figure 1, the vesicle of Example 1 is a transmission electron micrograph (uranyl acetate coloring, magnification 100,000 times).

2 is a transmission electron micrograph of the vesicle of Example 6 (uranyl acetate coloring, magnification 100,000 times).

3 is a transmission electron micrograph of the vesicle of Example 10 (uranyl acetate coloring, magnification 100,000 times).

4 is a transmission electron microscope photograph of the vesicle of Example 13 (uranyl acetate coloring, magnification 100,000 times).

5 is a transmission electron microscope photograph of the vesicle of Example 16 (uranyl acetate coloring, magnification 100,000 times).

6 is a transmission electron micrograph of the vesicle of Example 17 (uranyl acetate coloring, magnification 100,000 times).

[Purpose of invention]

[Technical field to which the invention belongs and the prior art in that field]

The present invention relates to a nonionic vitamin E derivative capable of forming an amphiphilic polymer vesicle and a method for preparing the same. More specifically, nonionic vitamin E or polyethoxyl which can form amphiphilic polymeric vesicles with improved thermodynamic stability and good in vivo compatibility and antioxidant activity protecting biological cells from harmful free radicals. A related vitamin E derivative and a method for preparing the same, and an amphiphilic polymer vesicle obtained therefrom.

In cosmetics and external ointments for skin, oily substances such as triglycerides, esters, and paraffins are used in large amounts as emollients in order to prevent moisture evaporation of the skin. However, these oily substances are incompatible with water and water-soluble components, which are the main bases such as cosmetics and skin ointment, due to their structural characteristics, and therefore, additional use of surfactants is inevitable for stability and long-term preservation of emulsified products.

Surfactants are called amphiphilic or amphiphatic molecules in which a lyophilic group and a lyophilic group are simultaneously present in a molecule with chemical solvents. It consists of several polar groups. These molecules have an interfacial activity in solution, and above the critical micelle concentration, the molecules gather to form spherical, rod or layer micelles, and these micelles solubilize non-aqueous materials.

On the other hand, there are many known amphiphilic structures among natural biological components, for example, various glycolipids, proteins, phospholipids, saponins, bile acids, and the like, which exhibit surface activity, can be listed. They are derived from living organisms and are called "biosurfactants," and have improved solubility in water, so that they can effectively exert physiologically active functions in the living body and facilitate the absorption of other substances. In particular, the phospholipid is a component of the membrane lipid (membrane lipid) has a hydrophobic portion composed of two lipid chains to form liposomes easily, and because it is a component of a living cell itself, it is an excellent safety or moisturizing component to be. However, since phospholipids are composed of chains with double bonds, they are easily oxidized to peroxides, causing cell damage and promoting aging.

Therefore, a lot of efforts have been made to develop materials capable of forming vesicles, which are minute membrane vesicles at the molecular level, such as liposomes by phospholipids, using alkyl group components other than phospholipids. A vesicle is the simplest functional membrane defined as a bilayer smetic mesophase, exhibits surfactant activity and can retain water within the drug delivery system and photochemical solar energy system. Applications have been attempted in chemical solar energy systems, reactivity control systems, and the like.

Accordingly, research on surfactants is focused on the development of synthetic amphiphilic materials having vesicle-forming ability such as phospholipids. Becyclocer, a synthetic amphiphilic molecule, was first proposed in 1975 by JM Gebicki and M. Hicks, a thin film of oleic acid and linolenic acid. It was formed by shaking in buffer. However, the closed double layer membrane structure has a pH of 6 It was unstable outside the range of 8, and had a problem that concentration by centrifugation was impossible. Subsequently, vesicles formed by ultrasonic dispersion of dialkyl dimethyl ammonium salts and dihexadecyl phosphate by Kunitake et al. Have been proposed, which form stably at a full range of pH. It became. However, these synthetic surfactant vesicles are difficult in their application because they are thermodynamically unstable and precipitate out of fusion upon long term storage.

Recently, in order to improve the stability of synthetic vesicles, "polymerization of vesicles" has been proposed, and the polymerized form of amphiphilic molecules composed of a single line of alkyl chains before the concept of vesicles is known as "polysorb ( ploysoap) ", but is being actively studied with the concept of such polymerized vesicles.

[Technical problem to be achieved]

Accordingly, the present inventors have focused on the development of polymerized amphiphilic vesicles, and have sufficient hydrophobicity and orientation properties so that vitamin E or polyethoxylated vitamin E can be used as the hydrophobic group of the vesicle. And cationic vitamin E derivatives or polyethoxylated vitamin E derivatives which have already been prepared by introducing a cationic group of quaternary nitrogen into vitamin E or polyethoxylated vitamin E. A method and an amphiphilic polymer vesicle having an antioxidant action formed therefrom have been filed under the name of the invention (Patent Application No. 96-11673). Furthermore, the present inventors have found that the cationic amphiphilic vitamin E derivative in which the cationic group of the quaternary nitrogen introduced by the patent application 96-11673 is introduced has excellent vesicle forming ability, but the monomer and the polymer are positive (+) In consideration of the possibility of compatibility with many negative or positive ionic components in vivo, research has been conducted on the development of nonionic amphiphilic vitamin E derivatives. .

However, in the case of nonionics, the electrostatic force is weak, and unlike cationic amphiphilic monomers, in general, monoalkyl type monomers cannot produce stable vesicles, and must be distinguished to form vesicles that exhibit stability. Many times you can. The present inventors have diligently researched for the purpose of providing a nonionic vitamin E derivative capable of forming amphiphilic vesicles having excellent thermal stability even with monomers themselves. As a result, acrylic acid derivatives and methacrylic acid in vitamin E or polyethoxylated vitamin E The present invention has been accomplished by discovering that the above object can be achieved by introducing a derivative or a crotonic acid derivative.

Accordingly, an object of the present invention is to provide a nonionic vitamin E or a polyethoxylated vitamin E derivative which is capable of forming an amphiphilic vesicle with improved thermodynamic stability and excellent biocompatibility and having antioxidant bioactive function. will be.

It is another object of the present invention to improve the thermodynamic stability obtained by polymerizing the above-mentioned nonionic vitamin E or polyethoxylated vitamin E derivatives, to improve in vivo compatibility, and to have an amphiphilic polymer vesicle having antioxidant bioactive function. To provide.

[Configuration and Function of Invention]

The above object can be achieved by a compound of formula (I):

Wherein n is 0 An integer of 50; A is -CH ₂ -CH (CH ₃ )-or CH = C (CH ₃ )-; B is CH ₃ bonded to at least one of 5-, 7- and 8- positions; m is 1 An integer of 3; R is an acrylic acid derivative, methacrylic acid derivative or crotonic acid derivative represented by the following formula (2).

Wherein R ₁ and R ₂ are H or CH ₃ .

In addition, the amphiphilic polymer vesicle according to the present invention may be represented by the following formula (3).

Wherein n, A, B, M and R are the same as defined in Chemical Formulas 1 and 2, and P represents the degree of polymerization of the polymer and is an integer of 10-6,000.

The compound of Formula 1 may be obtained by reacting a vitamin E or polyethoxylated vitamin E derivative of Formula 4 with an acrylic acid derivative, methacrylic acid derivative or crotonic acid derivative represented by Formula 2 in the presence of a catalyst. .

Wherein A, B, n and m are the same as defined in formula (1).

Vitamin E used in the production method of the present invention is natural vitamin E or synthetic vitamin E extracted from the seeds of plants, synthetic vitamin E is - Tocopherol, - Tocopherol, - Tocopherol or - Tocopherol may be selected.

In addition, the added mole number of ethylene oxide in the vitamin E or polyethoxylated vitamin E derivative used in the preparation method of the present invention is zero for the fluidity and crystallinity necessary for the water solubility and the regular arrangement of the amphiphilic polymer vesicle obtained. A range of 50 moles is suitable.

In addition, in the above production method, the reaction is 0 30 It is carried out in the temperature range of. The reaction is carried out in the presence of a catalyst, for example triethylamine can be used as the reaction catalyst.

In addition, the amphiphilic polymer vesicle of the formula (3) according to the present invention can be obtained by ultrasonic dispersion of the nonionic vitamin E derivative itself of formula (1) prepared by the above method, and the ultrasonic dispersion of the nonionic vitamin E derivative It can also be obtained by polymerizing after that. When polymerizing nonionic vitamin E derivatives, the free radical initiator may be used to 80 The reaction is carried out in the temperature range or polymerized by irradiation with ultraviolet rays. At this time, the polymerization degree is 10 for proper fluidity and arrangement stability. The range of 6,000 is preferred.

Examples of free radical initiators used in the preparation of amphiphilic polymer vesicles include, for example, potassium persurfate (K ₂ S ₂ O ₈ ), hydrogen peroxide (H ₂ O ₂ ), azo Azoisobutyronitile (AIBN), azobis (4-cyanovaleric acid) (Azobis (4-cyanovaleric acid)) can be used.

Compound of formula (1) provided according to the above production method is, by combining a non-ionic group of acrylic acid derivatives, methacrylic acid derivatives or crotonic acid derivatives with a hydrophobic group consisting of vitamin E or polyethoxylated vitamin E, ultrasonic dispersion A vesicle may be formed by, for example, injection of a cylinder, and may be easily polymerized by radical or ultraviolet radiation by having a double bond which may be polymerized in a molecule. Amphiphilic polymer vesicles provided by the present invention are intramolecular nonionic groups, and have good compatibility with effective water-soluble and oil-soluble substances in the base when used in medicines and cosmetics, and the affinity of these active substances with skin. By improving the effect can be improved. In addition, it has improved oxidative stability and moisturizing properties that vitamin E does not have compared to vitamin E, and furthermore, it has excellent bio stability and antioxidant power, so that physiologically active substances that are easily oxidized can be preserved more stably and delivered to the living body. By preventing the oxidation of the biofilm can delay the aging of the living body.

Hereinafter, an Example is given and this invention is demonstrated concretely. However, these examples only illustrate the present invention, and the present invention is not limited only to these examples.

(1) Synthesis of Nonionic Vitamin E Derivatives

Example 1

Polyethoxylated vitamin E (n = 2, 24.1 g, 46.4 mM) was dissolved in chloroform, and then acryloyl chloride (4.6 g, 51.0 mM) was added dropwise on ice. After the dropwise addition, the mixture was reacted at room temperature for 8 hours. The reaction solution was washed with 300 ml of ionized water and 5% sodium hydrogen carbonate (NaHCO ₃ ) solution, and again with ionized water. After washing, the resultant was dehydrated with anhydrous sodium sulfate and distilled under reduced pressure to obtain polyethoxylated vitamin E acrylate (24.8 g, yield 93%). The structure of the obtained compound was TLC. Confirmed by NMR and IR.

Example 2

Polyethoxylated vitamin E (n = 5, 14.3 g, 19.6 mM) and acryloyl chloride (4.6 g, 51.0 mM) were carried out in the same manner as in Example 1 to obtain a compound of formula 1 (yield 95 %)

Example 3

Polyethoxylate vitamin E (n = 10, 18.6 g, 19.6 mM) and acryloyl chloride (4.6 g, 51.0 mM) were carried out in the same manner as in Example 1 to obtain a compound of formula (I). %)

Example 4

Polyethoxylated vitamin E (n = 20, 14.3 g, 19.6 mM) and acryloyl chloride (4.6 g, 51.0 mM) were subjected to the same method as Example 1 to obtain a compound of formula 1.

Example 5

Vitamin E (24.1 g, 56.0 mM) was dissolved in chloroform, and methacryloyl chloride (5.3 g, 51.0 mM) was added dropwise on ice. After the dropwise addition, the mixture was reacted at room temperature for 8 hours. The reaction solution was washed with deionized water and 300 ml of 5% sodium hydrogen carbonate solution, and then with ionized water. After washing, it was dehydrated with anhydrous sodium sulfate and distilled under reduced pressure to obtain polyethoxylated vitamin E acrylate (25.7 g, yield 94%). The structure of the obtained compound was confirmed by TLC, NMR and IR.

Example 6

Polyethoxylated vitamin E (n = 5, 14.3 g, 19.6 mM) and methacryloyl chloride (5.3 g, 51.0 mM) were carried out in the same manner as in Example 5 to obtain a compound of formula (I). 95%)

Example 7

Polyethoxylated vitamin E (n = 10, 18.6 g, 19.6 mM) and methacryloyl chloride (5.3 g, 51.0 mM) were carried out in the same manner as in Example 5 to obtain a compound of formula (I). 93%)

Example 8

Polyethoxylated vitamin E (n = 20, 14.3 g, 19.6 mM) and methacryloyl chloride (5.3 g, 51.0 mM) were subjected to the same method as Example 5 to obtain a compound of formula (I). 91%)

Example 9

Polyethoxylated vitamin E (n = 10, 18.6 g, 19.6 mM) and crotonyl chloride (5.3 g, 51.0 mM) were carried out in the same manner as in Example 5 to obtain a compound of formula 1 (yield 92%) . The structure of the obtained compound was TLC. Confirmed by NMR and IR.

(2) Synthesis of Amphiphilic Polymer Blessicle

Example 10

Polyethoxylated vitamin E acrylate (n = 2, 1.0 g) was ultrasonically dispersed in a mixed solution of 180 ml of ion-exchanged water and 20 ml of ethanol, and then degassed in the reactor with nitrogen. After degassing, warm the reactor to 70 80 After maintaining, the polymer polymerization was carried out by adding 10 mg of azoisobutyronitrile (AIBN), a radical polymerization initiator, four times at 2 hour intervals for a total of 8 hours to obtain a polymer vesicle. The structure of the obtained polymer vesicle was confirmed by IR, NMR and GPC. As a result, the peak of δ 6.40-5.30 (m, 3H), the hydrogen peak of the double bond, disappeared, and the ethylene oxide peak of δ 3.80-3.60 and δ 2.15, 2.11, The peaks of the three methyl groups, which are the substituents of the benzene ring of 2.00, shifted to the left 0.2 ppm and existed more slowly than the nonionic vitamin E derivatives.

Example 11

Polyethoxylated vitamin E acrylate (n = 5, 1.0 g) was ultrasonically dispersed in 200 ml of ion-exchanged water, and then degassed in the reactor with nitrogen. After degassing, warm the reactor to 70-80 During the polymerization, 10 mg of potassium persulfate (K ₂ S ₂ O ₈ ), a radical polymerization initiator, was added four times at 2 hour intervals to polymerize for a total of 8 hours to obtain a polymer vesicle. The obtained polymer vesicles were identified by IR, NMR, and GPC. As a result, peaks of δ 6.40-5.30 (m, 3H), the hydrogen peaks of the double bonds disappeared, and ethylene oxide peaks of δ 3.80-3.60 and δ2.15, 2.11 , The peaks of the three methyl groups, the substituents of the benzene ring of 2.00, are shifted to the left by 0.2 ppm and present in a gentler form than the nonionic vitamin E derivatives.

Example 12

Polyethoxylated vitamin E methacrylate (n = 2, 1.0 g) was polymerized in the same manner as in Example 10 to obtain a polymer vesicle.

Example 13

Polyethoxylated vitamin E methacrylate (n = 10, 1.0 g) was polymerized in the same manner as in Example 11 to obtain a polymer vesicle.

Example 14

Polyethoxylated vitamin E crotonate (n = 10, 1.0 g) was polymerized in the same manner as in Example 11 to obtain a polymer vesicle.

Example 15

Polyethoxylated vitamin E acrylate (n = 5, 0.01 g) was ultrasonically dispersed in 2 ml of ion-exchanged water, and then degassed in a UV reactor with nitrogen. After degassing, 350W of ultraviolet rays were irradiated for 2 hours to obtain a polymer vesicle. As a result of confirming the structure of the obtained polymer vesicle by IR, NMR and GPC, the peak of δ 6.40-5.30 (m. 3H), the hydrogen peak of the double bond, disappeared, and the ethylene oxide peak of δ 3.80-3.60 and δ 2.15, 2.11, The peaks of the three methyl groups, which are the substituents of the benzene ring of 2.00, shift to the left of 0.2 ppm and exist in a gentler form than the nonionic vitamin E derivatives.

Example 16

0.5 g of n = 2 and 0.5 g of n = 5 in the polyethoxylated vitamin E acrylate were mixed and ultrasonically dispersed in a mixed solution of 180 ml of ion-exchanged water and 20 ml of ethanol, and the inside of the reactor was degassed with nitrogen. After degassing, warm the reactor to 70-80 After maintaining, the solution was polymerized for a total of 8 hours by adding 10 mg of azoisobutyronitrile four times at 2 hour intervals to obtain a polymer vesicle. As a result of confirming the structure of the obtained polymer vesicle by IR, NMR and GPC, the peak of δ 6.40-5.30 (m. 3H), the hydrogen peak of the double bond, disappeared, and the ethylene oxide peak of δ 3.80-3.60 and δ 2.15, 2.11, The peaks of the three methyl groups, the substituents of the benzene ring of 2.00, shifted 0.2 ppm to the left, presenting a gentle form of the nonionic vitamin E derivative.

Example 17

0.5g of n = 0 and 0.5g of n = 10 in the polyethoxylated vitamin E acrylate were ultrasonically dispersed in 200 ml of 10% ethanol-ion-exchanged water, and the reactor was degassed with nitrogen. After degassing, warm the reactor to 70-80 After maintaining, the solution was polymerized for a total of 8 hours by adding 10 mg of potassium persulfate four times at 2 hour intervals to obtain a polymer vesicle. The structure of the obtained polymer vesicle was confirmed by IR, NMR and GPC. As a result, the peak of δ 6.40-5.30 (m. 3H), which is a hydrogen peak of the double bond, disappeared, and the ethylene oxide peak of δ 3.80-3.60 and δ 2.15, 2.11, The peaks of the three methyl groups, the benzene ring substituents of 2.00, shift to the left of 0.2 ppm and exist in a gentler form than the nonionic vitamin E derivatives.

Example 18

In the polyethoxylated vitamin E methacrylate, 0.5 g of n = 5 and 0.5 g of n = 10 were mixed and polymerized in the same manner as in Example 11 to obtain a polymer vesicle.

Example 19

0.5g of n = 5 and 0.5g of n = 20 were mixed in the polyethoxylated vitamin E methacrylate and polymerized in the same manner as in Example 11 to obtain a polymer vesicle.

Example 20

Polyethoxylated vitamin E acrylate (n = 2, 0.3g) and polyethoxylated vitamin E methacrylate (n = 20, 0.7g) were mixed and polymerized in the same manner as in Example 10 to obtain polymer polymers. Obtained a cycle.

Example 21

Polyethoxylated vitamin E acrylate (n = 5, 0.7g) and polyethoxylated vitamin E methacrylate (n = 5, 0.3g) were mixed and polymerized in the same manner as in Example 11 to obtain polymer polymers. Obtained a cycle.

Example 22

Polymer vesicles were obtained by polymerizing in the same manner as in Example 15 by mixing 0.002 g of n = 2 and 0.008 g of n = 20 in the polyethoxylated vitamin E acrylate.

Example 23

Polyethoxylated vitamin E acrylate (n = 10, 0.7g) and polyethoxylated vitamin E methacrylate (n = 5, 0.3g) were mixed and polymerized in the same manner as in Example 11 to obtain polymer polymers. Obtained a cycle. When the structure of the obtained polymer vesicle was confirmed by IR, NMR and GPC, the peak of δ 6.40-5.30, which is a double bond hydrogen peak of polyethoxylated vitamin E acrylated disappeared, and polyethoxylated vitamin E methacryl The peaks of the hydrogen bond peaks of δ 6.25, 5.70 disappear, and the peaks of the three methyl groups, which are the substituents of the ethylene oxide peak and the benzene ring of δ2.15, 2.11, and 2.00, move to the left of 0.2 ppm, resulting in nonionic vitamin E derivatives. Exists in a more gentle form.

[Test Example 1]

[Creation confirmation test of vesicle]

The vesicle formation of the nonionic vitamin E derivatives according to the present invention was observed by transmission electron microscopy (TEM (JEOL, TEM-100CX). The vesicles can be obtained by ultrasonic dispersion in aqueous or ethanol aqueous solution above the phase transition temperature of each material. In the case of a polymer, a vesicle may be formed after ultrasonic dispersion.

Electron micrograph of the vesicle according to the embodiment 6 degrees. As a result, the nonionic vitamin E derivative was excellent in vesicle formation ability and stability by itself, and the vesicle stability was further improved by polymerizing.

[Test Example 2]

[Thermal Stability Test]

The amphipathic polymer vesicles obtained in Examples 10-23 were all 37 Stable for 6 months at, and also 90 All of them, which were cooled to room temperature after being heated, were stable for at least 3 months.

[Test Example 3]

Antioxidant Test

The antioxidant powers of the nonionic vitamin E derivatives obtained in Example 5 of the present invention and the amphiphilic polymer vesicles obtained in Examples 11 and 17 were measured by the following two methods. Also, for effectiveness comparison, vitamin E, vitamin E acetate, , The antioxidant power of the amphipathic polymer vesicle obtained by polymerizing '-dihexadecyl-oxyglyceryl-oxycarbonylmethyl-2- (methacryloxy) ethyldimethylammonium chromide (DHEMEA) was also measured.

[Test Example 3-1]

[Antioxidant Test Using DPPH]

DPPH (diphenylpicrylhydrazyl: diphenyl picryl hydrazyl) is a powerful radical reaction inhibitor that reacts with radicals to form a stable compound. This experiment uses this property.

Add about 50ml of DPPH to the test tube, add the measuring material and place it in the water bath for about 30 minutes. Was maintained. At this time, the sample without color change means that there is no antioxidant, and when it is difficult to measure with the naked eye, it was measured by UV. The test results are shown in Table 1.

[Test Example 3-2]

[Antioxidant Test Using Linoleic Acid]

Linoleic acid is a compound with a double bond, which is easily oxidized to a peroxide. This experiment uses this property. A control sample solution containing 2.88 ml of 2.5% linoleic acid ethanol solution and 9 ml of 40 mM phosphate buffer (PH 7.0) was added to 120 ml of ethanol. Stored in the dark. Samples were taken at regular time intervals and the time at which the samples did not change was defined as "the duration of antioxidant activity".

0.1 ml of the mixture prepared above, 9.7 ml of 75% ethanol and 0.1 ml of 30% amminothiocyanate were added. At this time, 0.1 ml of each sample was added dropwise, and after 3 minutes, UV absorbance was measured at 50 nm. The lower the absorbance value, the better the antioxidant properties. The test results are shown in Table 1.

From the results of Table 1, it can be seen that the nonionic vitamin E derivatives and the amphipathic polymer vesicles of the present invention exhibit an antioxidant capacity similar to that of vitamin E.

Claims (6)

A nonionic vitamin E derivative represented by the following formula (1): [Formula 1] Wherein n is 0 An integer of 50; A is -CH ₂ -CH (CH ₃ )-or CH = C (CH ₃ )-; B is CH ₃ bonded to at least one of 5-, 7- and 8- positions; m is 1 An integer of 3; R is an acrylic acid derivative, methacrylic acid derivative or crotonic acid derivative represented by the following formula (2). [Formula 2] Wherein R ₁ and R ₂ are H or CH ₃ . Amphiphilic polymer vesicles represented by the following general formula (3) comprising a nonionic vitamin E or polyethoxylated vitamin E derivative according to claim 1 as a repeating unit: [Formula 3] Wherein n, A, B, M and R are the same as defined in Chemical Formulas 1 and 2, and P represents the degree of polymerization of the polymer and is an integer of 10-6,000. Formula 1 according to claim 1 characterized by reacting the vitamin E or polyethoxylated vitamin E derivative of the formula (4) and the acrylic acid derivative, methacrylic acid derivative or crotonic acid derivative represented by the formula (2) in the presence of a catalyst Preparation of nonionic vitamin E derivatives of [Formula 4] Wherein A, B, n and m are the same as defined in formula (1). The method of claim 3, wherein the vitamin E is a synthetic vitamin E or natural vitamin E. The method of claim 4 wherein the synthetic vitamin E is - Tocopherol, - Tocopherol, - Tocopherol or - Method for producing a tocopherol. The reaction temperature of claim 3, wherein the reaction temperature is zero. 30 Range, the catalyst being triethylamine.