JPH013192A - Furan compounds and oil and fat antioxidants containing them as active ingredients - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to a furan compound having an antioxidant effect on fats and oils, and furthermore to an antioxidant for fats and oils containing such a compound as an active ingredient. Alternatively, it can be used in fields where oxidation of oils and fats, such as foods used for animals, cosmetics, or pharmaceutical additives, is beneficial.

[Prior art and its problems] Conventionally, synthetic compounds such as BHT or BHA and natural tocopherols (including dl-tocopherol) have been used to prevent the oxidation of natural oils and fats ingested by humans or animals. Recently, the latter has been gaining importance from the perspective of using materials that are closer to nature. In addition, it is sometimes effective to coexist with citric acid, ascorbic acid, etc. in the hope of having an auxiliary effect, but it is an acidic substance (solubility problem), and ascorbic acid used in aqueous form may be contaminated with metal ions. [Means for solving the problem] The present inventors have long experience in preventing oxidation of oils and fats. As a result of extensive research, it was discovered that compounds having the general formula and the general formula CH-○A have excellent oil and fat oxidation inhibitory effects, and the present invention was completed.

In the above general formulas (I) and (II), R□ represents a hydrogen atom, a linear or branched alkyl group having 1 to 24 carbon atoms, an alkenyl group, a glycolyl group, or a cholesteryl group, and R2 represents a linear or branched alkyl group, alkenyl group, glycolyl group, cholesteryl group or group having 1 to 24 carbon atoms, A is a hydrogen atom, -p(=o) (OH)2, -
P (=0) (OH) -0-(CH2)z -B
or a group, X and Y are the same or different and represent a hydrogen atom or a methyl group, and B is -Nl(2 or -N(CH,)3
shows. m and n represent integers of 2 to 14.

Some of the compounds having formula (I) and formula (II) are compounds known to exist naturally [RoL, Klass et al., Rivit 9, p. 1004 (1974);
Vol. 0, p. 695 (1975); Vol. 17, p. 828 (
(1977); Watanabe et al. (1984) et al.
Its action is unknown biologically or technologically.

The present inventors synthesized compounds having the above formulas (I) and (II), studied their antioxidant effects on fats and oils under various conditions, and discovered their effectiveness.

As described above, the compound group according to the present invention is a fatty acid containing furan (hereinafter abbreviated as FA). As is clear from the above literature, FA is widely distributed in freshwater fish, and is also found in cod, cod, etc.
Cholesterol esters and triglycerides are also contained in small amounts in marine fish such as salmon, and these fish and their oils (cod liver oil, etc.) have been enjoyed for many years, but there are problems in terms of safety, taste, aroma, etc. There is no.

FA has almost the same carbon chain length as natural fatty acids, and by having carboxylic acid in the same position, it has extremely good affinity with fats and oils in all conditions, regardless of the presence or absence of water. Furthermore, the position of the furan ring is almost the same as the position occupied by the double bond of the unsaturated fatty acid, which is convenient for interaction during the oxidation reaction. In this way, compound (II) is actively mixed into emulsified state, micelles or liposomes, and not only exhibits a remarkable antioxidant effect, but also significantly enhances the action of commonly used antioxidants such as tocopherol. FA does not react with diphenylvicrylhydrazyl (DPPH), and when added to linoleic acid hydropermicide, P
Since this acid reduces Ov, it does not act by stopping the radical chain reaction, but decomposes hydroperoxide and exhibits an antioxidant effect.

The esters of the general formula (I) are synthesized from free acids by conventional methods. In addition, free acids are CM, S, and F synthesized according to known methods.

Leekenzie et al., Chemistry and Physics of Lipids, Vol. 20, p. 1 (1978); C, H
, Rahn et al., Journal of Organic Chemistry, Vol. 44, p. 3420 (1979); R.

Schodel et al., Helvetica Kimi Power Acta Volume 68, 162
4 (1985)).

For some of the compounds having the general formula (1,I), a glycero A compound substituted with FA at the 1.2-position can be synthesized by dehydrating and condensing two molecules of FA required for A-substituted chrycerol. In addition, other compounds are obtained by using the 5n-II compound obtained in the same manner as a raw material, converting it into a lyso form by the enzymatic reaction of phospholipase A2, and dehydrating and condensing the desired fatty acid at the 2-position, which has become free 10f-1, again. can get.

[Example] Next, the present invention will be explained in more detail with reference to Examples.
The present invention is not limited thereby.

Example 1 Synthesis of di-9-(3,4-dimethyl-5-pentyl-2-furyl)nonanoylphosphatidylcholine 3.4 mmol of L-d-glycerophosphorylcholine cadmium chloride salt was dissolved in 150-proof anhydrous chloroborum, and 8. 5 mmol of 9-(3,4-dimethyl-5-pentyl-2-furyl)nonanoic acid, 10 mmol of dimethylaminopyridine and 27 mmol of DCC were added, and 18
The reaction was completed after being left for some time. The product purified by silica gel column chromatography was found to be single by TLC, and the quantitative value of furan fatty acid methyl ester obtained by metalysis with anhydrous hydrochloric acid and methanol by gas chromatography was approximately 2 to 1 of phosphoric acid.

Example 2 9-(3,4-dimethyl-5-benzene 2
Synthesis of 0.012 mmol of the compound obtained in Example 1 of -furyl)nonanoyl-9,12-octadecadininoyl-phosphatidylcholine in 5 ml
Dissolved in ether-ethanol (19:1), O,1
ml of phospholipase A2 enzyme solution (1 mg enzyme 450 units/1 ml 0.2 mol Tris-HCl, pH 7,
5) and 0.05 ml of 0.2 mol cadmium chloride are added, sonicated for 5 seconds, and reacted at 37°C for 16 hours. After taking the aqueous layer and washing it with ether, the water was blown off and ethanol was added to transfer it. After removing the precipitate by centrifugation, the ethanol was distilled off and washed with ether, then dissolved in ethanol again to remove the ether. Additionally, collect the precipitate.

The obtained compound is a lyso compound in which the 2-position of the glyceryl group is free. This was added in 5 ml of anhydrous chloroform with 0.0
Acylation at the 2-position was performed using 2 mmol of linoleic acid, 0.02 mmol of dimethylaminopyridine, and 0.06 mmol of DCC. Purify by silica gel column chromatography. This showed a single spot on TLC and was treated with approximately 1 mol of phospholipase A2 enzyme.
An equivalent amount of linoleic acid is liberated. The quantitative ratio of FA and each ester of linoleic acid obtained by metatolysis was approximately 1:1, indicating that the compound was the desired compound.

Example 3 Mass spectra Di-8-(5-hexyl-2-
(Furyl) After treating octanoyl-phosphatidylcholine, phospholipase C was applied to liberate the 3-position of the glyceryl group, and t-butyldimethylsilyl chloride was reacted to form t-butyltrimethylsilyl ether. Mass spectra were measured.7' −(70+++eV
).

M/e: 701 (N-57), 351 (acyl+7
4), 281,277 (acyl), 207,165 (
Furan ring, base peak), 731. Mass spectrum of 2-di-balmitoyl-glycero-3-t-butyltrimethylsilyl ether M/e: 625 (
M-57), 313 (acyl+74), 239 (ac
yl)/11-Example 4 Antioxidant effect on methyl linoleate oil 0.01 g of methyl 8-(5-to≦sil-2-furyl)7r ctanoate (
When comparing the antioxidant effect when adding FA) with the same amount of α-tocopherol (TO), POV,
The initial COV (45° C. incubator, shielded from light) values showed good results.

Example 5 Antioxidant effect on safflower oil The effects of methyl 8-(5-hexyl-2-furyl) octanoate (FA) on safflower oil are as follows, demonstrating its effectiveness.

Safflower oil contained 0.026% α-tocopherol as determined by HPLC and ODC column fluorescence measurement, so the enhancement effect was investigated.

Add 2g of safflower oil and 0.02g of sample.

45°C1 incubator, shielded from light.

Example 6 Antioxidant effect of linoleic acid in aqueous micelle state g-(3゜4-dimethyl-5-benzene-2-furyl)nonanoic acid (FA) on linoleic acid in aqueous micelle state
Regarding the antioxidant effect of conjugated diene generated by radical reaction, 234 nm 0.0. At the same time, the remaining amount of linoleic acid was measured by gas chromatography.

The synergy with α-tocopherol was particularly potent.

70 mg of linoleic acid and 0.5 g of Tνeen 20 were added to 100 ml of phosphate buffer pH 6.9 to form micelles, each reagent was added, and a reaction was carried out at 24 to 26°C. The amount of residual linoleic acid was methylated with trimethylsilyldiazomethane after extraction with ether, and quantified by gas chromatography.

234nm 0. D. Changes over time and residual linoleic acid Example 7 Synthetic phosphatidylcholine Antioxidant effect of FA derivatives on liposomes - 111 Absorbance measurement 30 μmol of stearoylyl phosphatidylcholine synthesized in the same manner as in Example 2 was dissolved in chloroform. 1mol1% of the sample and 7.5μmol of 2,2'-azobis-(2,
After adding 4-dimethylnitrile (AMI/N) and evaporating the solvent under reduced pressure at room temperature to coat the flask wall in a film form, add 3 m] of 0.1N NaCl solution and shake to form liposomes. The reaction was carried out while warming to 50°C and stirring. Take 50 μm of reaction solution over time 4
ml of ethanol was added and the absorbance at 233 nm was measured.

F3: 9-(3,4-dimethyl-5-benzene-2-
Furyl) nonanoyl 18:2 : Riluoyl P: Phosphoryl C: Choline Example 8 Antioxidant effect of FA derivative (formula (II) compound) on autoxidation of soybean lecithin liposome --- Absorbance measurement exactly the same as Example 7 I did it. The average molecular weight of soybean lecithin was 775.

Example 9 Effect of furocarboxylic acid (FA) and tocopherol (TO) on autoxidation of synthetic phosphatidylcholine liposomes The reaction was carried out in exactly the same manner as in Example 7.

Example 10 Effect of FA on oxygen absorption during autoxidation of synthetic phosphatidylcholine liposomes The reaction was carried out under the same reaction conditions as in Example 7, except that the reaction temperature was maintained at 37°C, and the amount of dissolved oxygen was adjusted to YSI mode.
Measurements were made with a 153 oxygen monitor. Shown as residual oxygen amount (%).

FA and TO have the same meanings as in Example 9.

[Effects of the Invention] When the furancarboxylic acid compound is added in the form of an ester directly to fats and oils itself, an antioxidant effect is observed. Generally, natural oils and fats contain or intentionally add phenolic antioxidants such as tocopherol, and when a furancarboxylic acid compound is added to such a state, the effect is further enhanced. On the other hand, in the case of emulsified oils and fats that coexist with water, that is, aqueous micelles or liposomal oils, they maintain stability as they have polar groups, but it is difficult to use furancarboxylic acid compounds as antioxidants. As the free acid, even more preferably in liposomal form the general formula (I
By actively incorporating the glyceride type shown in I), the effectiveness can be further enhanced.

Claims (1)

[Claims] 1. A furan compound having the formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼. (In the formula, R_2 represents a linear or branched alkyl group having 1 to 24 carbon atoms, an alkenyl group, a glycolyl group, a cholesteryl group, or a group (numerical formula, chemical formula, table, etc.), and A' is -P(=O)(OH)_2, -P(=O
)(OH)-O-(CH_2)_2-B, X and Y are the same or different and represent a hydrogen atom or a methyl group, and B represents -NH_2 or -N(CH_3)_3. m and n
represents an integer from 2 to 14. ) 2. An oil and fat antioxidant containing a furan compound as an active ingredient having the formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or the formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼. (In the formula, R_1 represents a hydrogen atom, a linear or branched alkyl group having 1 to 24 carbon atoms, an alkenyl group, a glycolyl group, or a cholesteryl group, and R_2 represents a hydrogen atom having 1 to 24 carbon atoms.
24 linear or branched alkyl groups, alkenyl groups, glycolyl groups, cholesteryl groups or groups ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ where A is a hydrogen atom, -P(=O)( OH)_2,-
P(=O)(OH)-O-(CH_2)_2-B or group ▲There are mathematical formulas, chemical formulas, tables, etc.▼, X and Y are the same or different and represent a hydrogen atom or a methyl group, and B is -NH_2 or -N(CH_3)_3. m and n represent integers of 2 to 14. )