JPH0581577B2 - - Google Patents

Description

[Detailed description of the invention]

(Industrial Application Field) The present invention is directed to tropical turmeric (Curcuma longa).
It is produced by further demethylating tetrahydrocurcumin, which is produced by a reduction reaction using curcumin as a raw material, which is produced from a plant belonging to the Zingiberaceae family and is widely used as a yellow pigment in spices, curry powder, pickles, etc. This article relates to a new compound, dihydroxytetrahydrocurcumin, which has strong antioxidant activity and reduced yellow color, and an antioxidant containing this as an active ingredient. ,
It is applied to the food industry, cosmetics industry, pharmaceutical industry, etc. (Prior Art) Foods are generally manufactured from agricultural products, marine products, livestock products, and the like. However, during the storage and preservation processing of food raw materials and products, food raw materials and products deteriorate due to microbial contamination, putrefaction, and chemical effects, reducing their commercial value. For this reason, various food additives have been developed, as well as temperature treatment,
Methods such as deoxidation treatment, vacuum treatment, low temperature storage, and radiation treatment have been developed and put into practical use. Among these types of deterioration of food materials and products, the most problematic is the oxidation or peroxidation reaction of food components caused by oxygen in the air. Oxygen is important for maintaining the life of living organisms through respiration, but on the other hand, as it is a highly reactive compound, it reacts with various components in food, oxidizing or peroxidizing them, reducing their value as products. It is known that not only does it reduce the amount of carbon dioxide, but it also leads to the production of harmful substances in food. For example, nutritionally essential unsaturated fatty acids such as linoleic acid and linolenic acid contained in foods are easily peroxidized by oxygen in the air, producing peroxidized fatty acids and reactive radicals (free radicals). It has also been reported that carcinogenic substances such as malondialdehyde are produced. It has also been reported that peroxidized lipids, which are produced when unsaturated fatty acid molecules in lipids are peroxidized, alter proteins and nucleic acids in living organisms through chemical reactions, and have carcinogenic effects on living organisms. .
"(Mutagen and Toxicity" Vol. 5, p. 243 (1982); "Food Packaging" Vol. 17, p. 106 (1986)). To prevent such lipid peroxidation,
Packaging techniques such as oxygen absorbers to remove oxygen from packaging, vacuum packaging, and nitrogen gas displacement packaging are used. With the development of the chemical industry, synthetic antioxidants such as butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) have been commonly used. However, as the use of these synthetic antioxidants increases, food pollution increases, leading to major safety issues, and consumers increasingly reject synthetic antioxidants, leading to a decline in their usage. The current situation is that As mentioned above, it is thought that peroxides and carcinogens that are generated in animal bodies due to the toxic effects of oxygen have a negative effect on animal cells. is thought to be related to cell aging and, ultimately, to lifespan (free radical aging theory). Therefore, highly safe, naturally derived antioxidant substances are used as substances that support the body's antioxidant defense mechanism in foods, especially health foods and nutritional foods, as well as pharmaceuticals and cosmetics. It is highly anticipated in the technical field. However, natural antioxidants that are expected to be used in place of synthetic antioxidants that pose food pollution problems include vitamin C produced by chemical synthesis and vitamin E (tocopherol) extracted and purified from natural products. has just been put into practical use. These naturally derived antioxidants can be used in foods, medicines, etc.
In order to use them appropriately in cosmetics, etc., it is important to find natural antioxidants with different properties and use them under conditions that exhibit their respective characteristics. Plant-derived spices contain various compounds with antioxidant activity, and spices have been added to foods as food preservatives.
(Food Packaging, Vol. 19, No. 1, p. 97, 1987). However, many spices have strong aromas and colors, and these properties naturally limit the scope of their use when added to foods as antioxidants. For example, it has been used in food since ancient times. Curcumin contained in turmeric has antioxidant properties and has been used as a main component of spices produced from turmeric to preserve and stabilize foods. In other words, curcumin contains the phenolic hydroxyl group of vitamin E in its molecule and the beta-diketone structure, a new type of antioxidant found in the leaf wax of eucalyptus leaves.・Food Chemistry, Vol. 33, p. 777, 1985), it is known to exhibit strong antioxidant activity. On the other hand, in addition to the above-mentioned antioxidant properties, curcumin is known to be a pigment that exhibits a strong yellow color (Phytochemistry, Vol. 27, No. 4, 969).
Page, 1988), and is used as a food additive colorant, and is used to color curry powder and takuan. The present invention uses curcumin, which is naturally derived and has long been used in food as a spice, curry powder, and food coloring, as a starting material, and produces it using tetrahydrocurcumin obtained through a normal reduction reaction. However, it is applied as an antioxidant related to these naturally derived substances. (Problems to be Solved by the Invention) Various synthetic antioxidants currently in use and naturally derived antioxidant substances. By improving naturally derived substances with strong antioxidant properties to replace vitamin C and vitamin E, and supplying highly safe antioxidant substances, we hope to enable their application in foods, medicines, and cosmetics. It is something to do. In particular, curcumin, which is known as an antioxidant, has a strong yellow tone, so when it is applied to foods, etc., the food will be colored yellow. Therefore, curcumin cannot be used in food products that do not like coloring, no matter how strong its antioxidative properties are, and it inevitably suffers from a significant lack of versatility. In this way, substances with two types of properties are advantageous if they activate both properties at the same time, but their use is often limited in food products that require a variety of properties. is the current situation. As for antioxidants, a highly versatile and safe antioxidant that exhibits strong antioxidant activity and does not have coloring ability has not yet been developed. (Means for Solving the Problems) The present invention has been made to solve these problems all at once, and in particular, from the viewpoint of pollution prevention and ensuring safety, which have been drawing attention recently. Improving highly safe naturally derived substances that have been used in foods since ancient times and utilizing the useful properties of naturally derived substances is
This was done based on the idea that it would be more industrially useful than using synthetic chemicals. After considering various aspects, we focused on curcumin, a yellow pigment and antioxidant that is the main component of turmeric (genus Curcuma), which is produced from plants in nature and has been used in food and medicine since ancient times. , I got the idea that if I modified this chemically, I might be able to obtain the desired new antioxidant. As a result of extensive attempts at various chemical modifications, we obtained a new compound, dihydroxytetrahydrocurcumin, by demethylating tetrahydrocurcumin obtained by hydrogenating curcumin with boron tribromide, and completed the present invention. be. It was discovered that the substance of the present invention, dihydroxytetrahydrocurcumin, does not have a double bond related to color development in its molecule, so that the yellow tone is bleached. This property exactly overcomes the drawbacks of curcumin, which had limited its use due to its strong yellow color, and has been used industrially.
This is an epoch-making product that will expand its application to food additives, cosmetic additives, etc.

[Chemical formula] The antioxidant effect of dihydrotetrahydrocurcumin is thought to be due to the hydroxyl groups of the phenol rings at both ends and the diketone structure of the intermediate chain. The antioxidant activity analysis method used in the present invention is a chemical analysis method using a natural linoleic acid oxidation reaction system (Agricultural and Biological Chemistry, 45, p. 735, 1981), the peroxidation reaction of rabbit red blood cell membrane lipids, which is commonly used as an analytical method similar to biological systems, and the analytical method using the rat liver microsomal enzyme system (antimutagenesis and・Dihydroxytetrahydrocurcumin used in the present invention showed strong antioxidant activity in both analytical methods. . Next, a method for producing dihydroxytetrahydrocurcumin will be described. There is no problem with the reduction reaction of curcumin produced from turmeric, as it can be obtained through a normal hydrogenation reaction. The demethylation reaction of the obtained tetrahydrocurcumin with boron tribromide can be carried out as follows. That is, dihydroxytetrahydrocurcumin can be obtained by dissolving tetrahydrocurcumin in an organic solvent such as anhydrous dichloromethane acetone or alcohol, adding boron tribromide, and performing the reaction by cooling. To recover the dihydroxytetrahydrocurcumin thus obtained, conventional isolation and purification methods such as silica gel chromatography and high performance liquid chromatography can be used. Structural analysis of dihydroxytetrahydrocurcumin purified as a single component can be easily performed because the structure of the raw material, tetrahydrocurcumin, is clear. In other words, since the o-methoxyphenol structure of dihydroxytetrahydrocurcumin is demethylated to become an o-dihydroxyphenol structure, it is difficult to detect changes in its structure.
NMR (Nuclear Magnetic Resonance), IR (Infrared Absorption), MASS
This was confirmed from the results of instrumental analysis such as (mass spectrometry). The molecular weight was determined to be 344 by MASS. The data from the NMR analysis are shown in Table 1 below.

【table】

【table】

[Chemical] In addition, IR analysis revealed that the methoxy group absorption observed at 1033 cm ^-1 in tetrahydrocurcumin was not observed in dihydroxytetrahydrocurcumin. These results showed that the two methoxy groups of the raw material tetrahydrocurcumin were demethylated. Dihydroxytetrahydrocurcumin is a derivative of curcumin with the structure shown below, but as a result of searching the chemical literature, it was found that no reports have been found so far, and that it is a new compound.

[Chemical formula] The antioxidant activity of the dihydroxytetrahydrocurcumin thus obtained will be described. (1) Natural oxidation reaction system of linoleic acid The concentration of the test substance in the final reaction solution was adjusted to 20 μM (micromolar), and thiobarbilylic acid (TBA) was added.
When the production of linoleic acid oxide was measured using a coloring method, the results shown in FIG. 1 were obtained. When the degree of oxidation in the area where no antioxidant substance is added is 100%,
Dihydroxytetrahydrocurcumin was 23% and showed strong antioxidant activity. (2) Rat liver microsomal enzyme system This is a method used to evaluate antioxidant substances that act in vivo. The concentration of the test substance in the final reaction solution was 100 μM (micromolar). The results are shown in Figure 2. Dihydroxytetrahydrocurcumin, a substance of the present invention which has both a β-diketone structure and an o-dihydroxyphenol structure in its molecule, exhibited strong antioxidant activity similar to α-tocopherol. As mentioned above, the dihydroxytetrahydrocurcumin having antioxidant activity according to the present invention is a chemically modified naturally occurring curcumin pigment, and therefore has an imperceptibly low toxicity and is extremely safe. This antioxidant substance can be added to foods and cosmetics as it is, dissolved in a solvent, or dissolved in oil or essential oil. Alternatively, an extract containing curcumin group compounds (curcuminoids) extracted from turmeric can be used. An antioxidant composition containing the substance of the present invention may be obtained by directly carrying out a reduction reaction and a demethylation reaction, and this may be added to foods and cosmetics. The present invention will be explained below with reference to Examples, but these are illustrative and do not limit the present invention. Example 1 100 mg of tetrahydrocurcumin was dissolved in 10 ml of anhydrous dichloromethane in a 50 ml glass container. To this, 800 microliters of boron tribromide was added as a demethylating agent, and a reaction was carried out for 10 minutes while cooling to -70°C. Reduce the reaction solution to about 0
The temperature was returned to ℃ and 5 ml of cold water was added to stop the reaction. Add 20 ml of ethyl acetate to 15 ml of the reaction completed solution,
Dihydroxytetrahydrocurcumin was extracted. This operation was performed twice. 100 ml of saturated saline was added to the obtained extract to wash away the acid in the extract. After washing the remaining salt with 50 ml of water, anhydrous sodium sulfate was appropriately added to completely remove water in the extract. The thus obtained extract was purified using a preparative silica gel chromatography plate using a mixed solvent (chloroform:methanol:acetic acid ratio: 19:1:0.2 (volume ratio)).
The product was developed and purified. By repeating this method and successively removing impurities, 36 ml of dihydroxytetrahydrocurcumin was obtained. The structure and antioxidant activity of the obtained dihydroxytetrahydrocurcumin are as described above. (Effects of the Invention) The present invention is naturally derived and has been used as a food product since ancient times. This project proposes a new antioxidant substance that has been improved from curcumin, the yellow pigment of turmeric, as a starting material, and can be safely used in foods, cosmetics, and pharmaceuticals as an antioxidant that can replace conventionally produced synthetic antioxidants. It is used as a raw material for etc. The novel antioxidant substance according to the present invention has more subtle properties than curcumin, and is particularly excellent in that it has strong antioxidant activity and is not colored.

[Brief explanation of the drawing]

FIG. 1 shows the results of measuring antioxidant activity using the natural oxidation reaction system of linoleic acid. FIG. 2 shows the results of measuring antioxidant activity using the rat liver microsomal enzyme system.

Claims (1)

[Claims] 1. Dihydroxytetrahydrocurcumin, which is a novel compound represented by the following structural formula []. [Chemical formula] Structural formula [] 2 An antioxidant containing dihydroxytetrahydrocurcumin as an active ingredient, which is represented by the following structural formula []. [ ] Structural formula [ ]