JP2921730B2 - Gelling agent for organic solvents or fats and oils - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a gelling agent for organic solvents or fats and oils containing a cyclic dipeptide comprising a specific amino acid as an active ingredient.

[0002]

2. Description of the Related Art Heretofore, there have not been many studies and reports on oil-based gelling agents as compared with aqueous gelling agents. However, in recent years, among the oil-based gelling agents, 12-hydroxystearic acid obtained from castor oil as a raw material has been marketed as a waste oil treating agent, and development in this field has been progressing recently. However, 12-hydroxystearic acid is limited in the type of oily substance to be gelled, and the resulting gel tends to have a rough feel, and its application range is narrow.

On the other hand, to solve these problems, gelling agents utilizing various amino acids (for example, N-lauroyl-L-glutamic acid-α, γ-di-n-butylamide) have been developed. This is a compound that can gel various organic solvents and fats and oils by chemically modifying amino acids themselves or by selecting substances that react with functional groups such as amino groups and carboxyl groups. It is. Also, the gel strength has been studied a lot because it can be adjusted by preparing the amino acid derivative by performing the same treatment as described above. However, these amino acid-based oil-based gelling agents have mainly been linear peptide derivatives as described in, for example, JP-A-51-91884. In addition, these peptide derivatives were not always satisfactory with respect to gelling ability and feeling of the obtained gel.

[0004]

SUMMARY OF THE INVENTION The present inventors have made various amino acid compounds based on the present situation, and have conducted detailed comparison of the gel forming ability and the like. As a result, the present inventors have completed the present invention. It is. That is, an object of the present invention is to provide a gelling agent which is excellent in gelling ability as compared with conventional oil-based gelling agents and forms a gel having a good feel.

[0005]

In order to achieve the above object, the present invention provides a compound represented by the following general formula (1) comprising leucine and one selected from the group consisting of valine, leucine, isoleucine and phenylalanine. The gist of the present invention is a gelling agent containing a cyclic dipeptide as an active ingredient.

Embedded image [However, in the formula (1), A is (CH ₃ ) ₂ CH, (C
_{H 3) 2 CHCH 2, (} C 2 H 5) (CH 3) CH or

Embedded image It is. ]

The essential component in the gelling agent of the present invention is selected from the group consisting of leucine, an aliphatic neutral amino acid, and valine, leucine, isoleucine and phenylalanine, which are aliphatic or aromatic neutral amino acids. A species is a cyclic dipeptide in which a six-membered ring structure is formed by two amide bonds. Such a cyclic dipeptide is represented by the general formula (1).

The starting amino acids of the cyclic dipeptides of the present invention include those obtained by extracting acid, alkali or enzymatic hydrolysates of proteins derived from natural products, those isolated from fermentation and culture products of microorganisms, and those obtained by chemicals. Any of those obtained by the synthesis method may be used. The optical isomers can be used irrespective of the difference between the D-form, L-form and DL-form (racemic form). Available and convenient.

[0008] The cyclic dipeptide of the present invention can be synthesized by appropriately selecting the amino acids and using a known method. For example, the aliphatic or aromatic neutral amino acid is
After protecting the α-amino group which is one of the functional groups, amidation reaction with leucine is carried out to form a dipeptide, and then the protecting group of the α-amino group is eliminated, and finally a cyclic dipeptide is formed. As a protecting group for this, a benzyloxycarbonyl group (Z group), a t-butoxycarbonyl group (Boc group), a 9-fluorenylmethoxycarbonyl group (Fmoc group), a 3-nitro-2-pyridinesulfenyl group ( Npys group) and the like, but it is common to introduce a Z group which can be easily removed.
Introduction of the Z group can be carried out by benzyloxycarbonyl chloride (ZC
Using l), a reaction is performed simultaneously with an aqueous solution of sodium hydroxide by a Schoftten-Baumann reaction.

Next, the above-described leucine and the neutral amino acid into which the Z group has been introduced are combined with dicyclocarbodiimide (D
Amidation reaction at 40 ° C. for about half a day using CC),
A linear dipeptide derivative is prepared, and this is
Hydrogen gas is blown for several hours at about room temperature in the presence of a catalyst such as palladium carbon, nickel, or platinum using a hydrocarbon of about 0 as a solvent to perform deprotection. In this way, other methods of deprotection are generally acid treatment with trifluoroacetic acid or hydrogen anhydride, but in the case of elimination from short-chain peptides, a mild catalytic reduction method is often used. Used. After removing the catalyst from the reaction, mesitylene,
The cyclic dipeptide of the present invention (a cyclized product of leucine and the above-mentioned neutral amino acid) can be obtained as crystals by dissolving in dioxane, dichloromethane, tetrahydrofuran or the like and refluxing for several hours. The cyclic dipeptide can be further purified by recrystallization using a lower alcohol such as methanol or ethanol as a solvent.

The cyclic dipeptide of the present invention gels various organic solvents or fats and oils. Particularly, for halogen and aromatic organic solvents, leucine and any one of leucine, isoleucine and phenylalanine are used. A cyclic dipeptide is preferred, and a cyclic dipeptide of leucine and phenylalanine is particularly preferred. For oils and fats, a cyclic dipeptide of leucine and phenylalanine is more preferable.

The various cyclic dipeptides thus obtained are
One or more of these can be used as appropriate to form the gelling agent of the present invention. Further, the gelling agent of the present invention may contain known gelling agents, thickeners, waxes and the like in addition to the cyclic dipeptide. Known gelling agents include aqueous gelling agents such as pectin, sodium alginate, carrageenan, polyacrylic acid or sodium polymethacrylate, and also mocro, 12-hydroxystearic acid, N-lauroyl-L-glutamic acid- N-acyl- such as α, γ-di-n-butylamide
There are oil-based gelling agents such as amino acid-alkylamides, lipophilic sucrose fatty acid esters, dextrin fatty acid esters, starch fatty acid esters, dibenzylidene sorbitol, dibenzylidene xylitol, acrylic acid or methacrylic acid polymers.

Examples of known thickeners include gum arabic, xanthan gum, guar gum, tragacanth gum, locust bean gum, curdlan, gellan gum, flaxseed gum, carboxymethylcellulose, hydroxyethylcellulose and hydroxypropylmethylcellulose. Examples of known waxes include carnauba wax, candelilla wax, shellac wax, beeswax, sugarken wax, rice wax, cottonseed wax, sunflower wax, paraffin wax, montan wax, and bayberry wax. be able to.

The gelling agent of the present invention comprises the cyclic dipeptide in an amount of 20 to 100% by weight, preferably 50 to 100% by weight.
It is made by blending. If the amount is less than 20% by weight, it is not possible to exhibit an effective gelling ability as compared with a conventional oil-based gelling agent, or it is difficult to obtain a gel having a good feel. The gelling agent of the present invention, for organic solvents or fats and oils,
0.1 to 10% by weight / volume (unit weight of organic solvent or oil / fat: The addition weight of the gelling agent of the present invention per ml: Percentage of g is shown. The same applies hereinafter.), Preferably 0.1 to 5% by weight. /% By volume to have good gelling ability. If less than 0.1% by weight / volume, no gel can be obtained and 10% by weight / volume
If it exceeds, the crystallization tendency becomes large.

In the present invention, various organic solvents can be used. Halogen solvents and aromatic solvents are particularly preferable, and benzene solvents are preferable. Specific examples thereof include carbon tetrachloride, benzene, toluene, xylene, methoxybenzene, and the like. Chlorobenzene, nitrobenzene and the like. The fats and oils are preferably liquid to semi-solid at room temperature, and more preferably exhibit a liquid state, and are soybean oil, rapeseed oil, corn oil, safflower oil, sunflower oil, cottonseed oil, olive oil, palm oil, Linseed oil, castor oil, fish oil, lard, beef tallow, and processed fats and the like obtained by mixing, fractionating, or transesterifying them, and further include triacetin, tributyrin, tricaprylin, triglyceride comprising a mixed fatty acid of caprylic acid and capric acid, and the like Glycerides containing a single or mixed fatty acid having about 2 to 10 carbon atoms as a constituent fatty acid (may include diglyceride and monoglyceride).

A predetermined amount of the gelling agent of the present invention is added to the above-mentioned organic solvent or fats and oils, and if necessary, the mixture is heated to about 40 to 80 ° C., stirred and mixed and dissolved.
(25 ° C.), a gelled product can be prepared. The resulting gel-like material is not a fragile material such as agar or gelatin, but is in a uniform and smooth state. There is no fluidization.

In the following Synthesis Examples, Examples and Comparative Examples,% is by weight unless otherwise specified. Synthesis Example 1 58.6 g of L-valine was added to a 2N aqueous solution of sodium hydroxide 2
The mixture was dissolved in 50 ml, and ether (50 ml) was added as a solvent. After stirring at ice temperature for 10 minutes, 85.3 g of benzyloxycarbonyl chloride and 250 ml of a 2N aqueous sodium hydroxide solution were simultaneously added in 10 portions. This solution was transferred to a separating funnel, and the aqueous layer was separated while washing with ether. To this, add about 250 ml of ethyl acetate, and further add 1N hydrochloric acid 6
00 ml was added and stirred. Washing with water was repeated three times, and magnesium sulfate was added to the ethyl acetate layer to remove water. The water was removed by filtration with filter paper. The filtrate was placed in an eggplant flask, and ethyl acetate was distilled off under reduced pressure. Add 150ml of new ethyl acetate
The mixture was added while warming, and shaken while adding petroleum ether little by little. Petroleum ether is added until the liquid becomes turbid even after shaking, and this is left to cool in a refrigerator to recrystallize, and Z-L-valine (hereinafter, ZL-Val) is added.
70.8 g). On the other hand, L-leucine 30g
Was suspended in 300 ml of absolute ethanol, dried hydrogen chloride gas was introduced while cooling in ice water, and then allowed to stand at room temperature while avoiding moisture to obtain a hydrochloride, which was washed with cold ethanol and anhydrous ether successively. After drying under reduced pressure, the product was recrystallized from ethanol and ether and L-leucine ethyl ester [hereinafter abbreviated as L-Leu (O-Et)] 23.5.
g was obtained.

Next, L-Leu (O-Et) and ZLV
The reaction with al was performed. Add ZL-Val to the eggplant flask.
25.1 g and 400 ml of ethyl acetate were added, and the mixture was stirred in an ice bath. In addition, dicyclohexylcarbodiimide 22.7
g was added and stirred at room temperature for 1 hour, whereby the system became cloudy. In this state, 19.8 g of L-Leu (O-Et) was added, the mixture was stirred for 1 hour, and further heated to 40 ° C., and the reaction was continued overnight. 800 ml of ethyl acetate was added to the reaction solution,
After heating and stirring, the resulting precipitate was removed, and ethyl acetate was distilled off under reduced pressure to recrystallize. After cooling, suction filtration was performed to obtain crystals. The filtrate was dissolved in 800 ml of ethyl acetate, and treated in the same manner to obtain crystals, and both crystals were combined. This is vacuum dried to obtain L-leucine ethyl ester and ZL
-Val and a linear dipeptide derivative [hereinafter, ZL-
Val-L-Leu (O-Et)].
Obtained.

ZL-Val-L-Leu (O-Et)
15 g was dissolved in 500 ml of methanol, and 10
% Palladium on carbon 2% and added at room temperature for 6 hours,
De-Z grouping was performed by injecting hydrogen gas. Filtering off the catalyst,
After concentrating the filtrate, the resulting L-Val-L-Leu was obtained.
(O-Et) was dissolved in 400 ml of mesitylene (2,4,6-trimethylbenzene) and refluxed for 5 hours to effect a cyclization reaction. After the reaction, mesitylene was concentrated to 100 ml, and the precipitated crystals were separated by filtration with filter paper, washed with petroleum ether and dried under reduced pressure to obtain a crude product. This was further recrystallized with 100 ml of ethanol to obtain a cyclic dipeptide in which L-leucine and L-valine had a six-membered ring structure through two amide bonds [hereinafter, cyclo (L-Val-L-Le).
u)] (Sample No. 1) (10.2 g) was obtained.

The outline of the above reaction step is represented by the following formulas (2) and (3).

Embedded image

Embedded image

Synthesis Examples 2 to 8 ZL-Leu2 obtained according to the method described in Synthesis Example 1
Using 6.5 g and 19.8 g of L-leucine ethyl ester, the same treatment was carried out to obtain 2 L-leucine.
21.2 g of a cyclic dipeptide (hereinafter abbreviated as cyclo (L-Leu-L-Leu)) (sample No. 2) having a six-membered ring structure via two amide bonds was obtained. Further, in the same manner as in Synthesis Example 1, a cyclic dipeptide of L-leucine and L-isoleucine each having a six-membered ring structure via two amide bonds [hereinafter, cyclo (L-iLeu)
-L-Leu)] (Sample No. 3), a cyclic dipeptide of L-leucine and L-phenylalanine [hereinafter, c
yclo (L-Phe-L-Leu)] (Sample N
o. 4) a cyclic dipeptide of L-glycines [hereinafter abbreviated as cyclo (L-Gly-L-Gly)]
(Sample No. 5), cyclic dipeptide of L-valine [hereinafter abbreviated as cyclo (L-Val-L-Val)] (Sample No. 6), cyclic dipeptide of L-phenylalanine [hereinafter, cyclo (L -Phe-LP
he)) (Sample No. 7), and a cyclic dipeptide of L-glycine and L-valine [hereinafter, cyclo (L)
-Val-L-Gly)] (Sample No. 8).

EXAMPLE 1 Cyclic dipeptide of L-leucine and L-valine [cyc
lo (L-Val-L-Leu), sample no. The gelling ability of 1) for organic solvents or fats and oils was examined by the following method. That is, 300 mg of the cyclic dipeptide and 10 ml of an organic solvent or fats and oils were taken in a test tube with a lid, and heated.
After dissolution, the state when cooled to 25 ° C. was observed.
The entire content is in a gel state, and when the test tube is tilted, the liquid substance does not exude and does not fluidize. The gel is used as the gel. For the gelled substance, the critical gelation concentration (organic solvent or oil / fat The minimum weight of the cyclic dipeptide required to gel 1 ml of the class (percentage of g, unit is weight / volume%, hereinafter referred to as CGC) was determined. As a result, cy
Clo (L-Val-L-Leu) (Test No. 1) C
GC is 1.6% by weight / volume with respect to chloroform and 2.0% by weight / volume with respect to toluene, has a gelling ability with respect to an organic solvent, and is suitable as the gelling agent of the present invention. Was observed. In addition, all of the obtained gels had a uniform and smooth feel.

Example 2 Cyclo (L-Leu) was obtained in the same manner as in Example 1.
-L-Leu) (Sample No. 2) was examined for its gelling ability with respect to organic solvents or fats and oils, and its CGC was 2.0% by weight / volume with respect to carbon tetrachloride and 0.2% with respect to benzene. 4% weight / volume, 0.9% weight / toluene
% By volume, and 0.2% w / v based on soybean oil. From this, cyclo (L-Leu-LL-L)
eu) has a gelling ability with respect to organic solvents and fats and oils, and the obtained gels have a uniform and smooth feel, which proved to be suitable as the gelling agent of the present invention.

Example 3 Cyclo (L-iLe) was obtained in the same manner as in Example 1.
When the gelling ability of u-L-Leu) (sample No. 3) with respect to organic solvents or fats and oils was examined, its CGC was 1.8% by weight / volume with respect to carbon tetrachloride and 0% with respect to benzene. 0.4% w / v, 1.1% w / v based on toluene and 0.3% w / v based on soybean oil. From this result, cyclo (L-iLeu-L-
Leu) has a gelling ability with respect to organic solvents and fats and oils, and the resulting gels have a uniform and smooth feel, which proved to be suitable as the gelling agent of the present invention.

Example 4 Cyclo (L-Phe) was obtained in the same manner as in Example 1.
-L-Leu) (Sample No. 4) was examined for gelling ability with respect to organic solvents or fats and oils, and its CGC was 2.0% by weight / volume with respect to acetone and 2.0% with respect to ethyl acetate. Wt / vol%, 2.0 wt / vol% for chloroform, 2.0 wt / vol% for benzene, 0.5 wt / vol% for toluene, 0.3 wt for methoxybenzene / Vol%, 0.3 wt / vol% for chlorobenzene, 0.3 wt / vol% for nitrobenzene, 0.2 wt / vol% for tricaprylin, 0.2 wt% for triolein % W / v, and 0.1% w / v based on soybean oil. From these results, it is clear that cyclo (L-Phe-L-Leu) has a gelling ability with respect to organic solvents and fats and oils, and that the resulting gels have a uniform and smooth feel. It proved to be suitable as an agent.

Example 5 Cyclo (L-Val-L-Leu) (Sample No. 1):
40%, cyclo (L-Leu-L-Leu) (sample
No. 2): 40% and 12-hydroxystearic acid:
Heat the mixture consisting of 20% to 80 ° C and mix evenly,
Cooled to room temperature. Organic solvents or fats and oils containing 3% by weight and 8% by weight of this were prepared, and the presence or absence of gel formation was examined by the same method as in Example 1.
For chloroform, carbon tetrachloride, benzene, toluene, triolein and soybean oil, it was recognized that a gel having a uniform and smooth feel was obtained.

Example 6 Cyclo (L-Phe-L-Leu) (Sample No.
4): 50%, 12-hydroxystearic acid: 30
%, Sunflower wax: 10% and beeswax 10% were heated to 80 ° C., mixed uniformly, and cooled to room temperature. In the same manner as in Example 1, organic solvents or fats and oils containing 1% by weight, 7% by weight, and 10% by weight / volume were prepared, and the presence or absence of gel formation was examined. As a result, for acetone, ethyl acetate, chloroform, benzene, toluene, methoxybenzene, chlorobenzene, nitrobenzene, tricaprylin, triolein, soybean oil, and rapeseed oil, it was confirmed that a gel having a uniform and smooth feel was obtained. .

Comparative Example 1 12-hydroxystearic acid was added to acetone, ethyl acetate, chloroform, carbon tetrachloride, benzene, toluene, methoxybenzene, chlorobenzene, nitrobenzene, tricaprylin, triolein and soybean oil in the same manner as in soybean oil.
When 0% (w / v) was added and the gelling ability was examined in the same manner as in Example 1, the gelling ability was not dissolved in the organic solvent and dissolved in fats and oils, but showed a viscous fluid state. Did not give a uniform gel. Further, when the gelling ability was similarly examined by adding 2.0% by weight / volume of 12-hydroxystearic acid to the fats and oils, a gel was obtained, but the gel was brittle and brittle.

Comparative Example 2 Cyclo (L-Gly) was prepared in the same manner as in Example 1.
-L-Gly) (Sample No. 5), cyclo (L-Va)
IL-Val) (Sample No. 6), cyclo (LP)
he-L-Phe) (Sample No. 7) and cyclo
As a result of examining the gelling ability of (L-Val-L-Gly) (Sample No. 8) with respect to organic solvents or fats and oils, any of these cyclic dipeptides was found to be the organic solvent and fats and oils described in Comparative Example 1. , And did not form a uniform and smooth gel which was the object of the present invention.

[0029]

According to the present invention, a gelling agent having an excellent gelling ability with respect to various organic solvents, especially a halogen-based solvent and an aromatic solvent, particularly a benzene-based solvent, or an oil or fat, to form a uniform and smooth gel. Agent can be provided.

──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int. Cl. ⁶ , DB name) C09K 3/00 103 C11B 15/00 CA (STN) REGISTRY (STN)

Claims (4)

(57) [Claims] 1. A gelling agent for organic solvents or fats and oils containing leucine and one selected from the group consisting of valine, leucine, isoleucine and phenylalanine as an active ingredient, comprising a cyclic dipeptide represented by the following general formula (1): . Embedded image [However, in the formula (1), A is (CH ₃ ) ₂ CH, (C
H ₃ ) ₂ CHCH ₂ , (C ₂ H ₅ ) (CH ₃ ) CH or It is. ] 2. In the general formula (1), A is (CH ₃ )
₂ CH, (CH ₃ ) ₂ CHCH ₂ or The gelling agent according to claim 1, which is: 3. In the general formula (1), A is The gelling agent according to claim 2, which is 4. The gelling agent according to claim 1, wherein the organic solvent is a halogen-based solvent or a benzene-based solvent.