KR100682549B1 - Sesamol derivatives and process for preparing the same - Google Patents

Abstract

The present invention relates to sesamol derivatives represented by the following formula (1) and a method for preparing the same. More specifically, the sesamol derivative is prepared by reacting sesamol and adamantanol in an acid condition at an equivalent ratio of 1: 1.0 to 1.3, and recrystallization in a polar solvent.

The derivative is a substance having a strong antioxidant power can be used for the recovery and prevention of skin damaged by harmful free radicals, can prevent the aging of the biofilm, and can inhibit the production of unsaturated fatty acids and peroxides thereof.

Sesamol Derivative * Antioxidant * Peroxide * Adamantanol * Sesamol

Description

Sesamol derivatives and process for preparing the same {Sesamol derivatives and process for preparing the same}

The present invention relates to sesamol derivatives represented by the following formula (1) and a method for preparing the same. More specifically, the sesamol derivative is prepared by reacting sesamol and adamantanol in an acid condition at an equivalent ratio of 1: 1.0 to 1.3, and recrystallization in a polar solvent.

[Formula 1]

The function of cosmetics is to cleanse, beautify and health the skin and hair. In particular, many studies have been made to prevent the formation of fine wrinkles on the skin due to antioxidant activity, and many substances have been developed and used. As such substances, vitamins such as ascorbic acid and tocopherol, flavonoids extracted from various animals and plants are known.

Sesamol, another powerful antioxidant in nature, is the main component of sesame oil. Sesame oil is known to be less likely to produce acid than other oils, the reason for this phenomenon is due to the antioxidant efficacy of sesamol. However, sesamol also has a problem of being unstable when applied to the formulation, like other natural antioxidants, despite a variety of antioxidant efficacy.

Accordingly, the present inventors have studied to develop sesamol derivatives having improved stability to solve the above problems, and as a result, the antioxidant efficacy of sesamol is increased and stability is improved by introducing the adamantane group directly into sesamol. The present invention was completed.

Accordingly, it is an object of the present invention to provide sesamol derivatives having improved antioxidant efficacy and improved stability by introducing adamantane groups directly into sesamol.

Another object of the present invention is to provide a method for preparing the sesamol derivative.

In order to achieve the above object, the present invention is characterized by providing a derivative of sesamol represented by the following formula (1).

[Formula 1]

Hereinafter, the present invention will be described in more detail.

Sesamol derivatives according to the present invention are prepared by reacting sesamol and adamantanol in acid conditions at an equivalent ratio of 1: 1.0 to 1.3, and recrystallization in a polar solvent.

The method for preparing sesamol derivatives according to the present invention may be represented by Scheme 1 below;

In Scheme 1, it is preferable to react the sesamol and adamantanol under an equivalence ratio of 1: 1.0 to 1.3 under acidic conditions. At this time, if the equivalent ratio is less than 1: 1.0, the desired product cannot be obtained. If the ratio exceeds 1: 1.3, the amount of by-products and unreacted substances other than the desired product is increased.

In addition, the reaction temperature and the reaction time is preferably reacted for 1 to 2 hours at a temperature of 10 ~ 50 ℃. If it is less than 10 ℃ has a disadvantage that the reaction time is too slow, the reaction time is long and the content of unreacted material is increased, the reaction yield is lowered, the excess by-products are generated above 50 ℃.

In addition, the acid used in Scheme 1 may be hydrochloric acid, nitric acid, sulfuric acid, p-toluenesulfonic acid, benzenesulfonic acid, acetic acid, trichloroacetic acid, trichloroacetic acid, and the like, preferably sulfuric acid, trichloroacetic acid, It is to use trifluoroacetic acid.

In addition, as the solvent used in Scheme 1, an organic solvent such as dichloromethane, tetrahydrofuran, ethyl acetate, acetonitrile, chloroform, ethyl ether, trichloroethylene, benzene, toluene, etc. may be used, and the acid used may be a liquid. In this case, acid may be used as a solvent. Preferably, toluene is used or trichloroacetic acid and trichloroacetic acid are used as the solvent and the acid.

When the reaction is completed, recrystallization is performed using a polar solvent, and the polar organic solvent used herein is not particularly limited, but for example, methanol, ethanol, isopropanol, acetone, acetonitrile, water and the like.

Sesamol derivatives according to the present invention exhibit improved antioxidant activity than sesamol alone.

Sesamol derivatives of the present invention may be applied to cosmetic and pharmaceutical compositions. On the other hand, when used in medicine, those skilled in the art can easily appropriately limit the amount of use according to the condition of the patient, the degree of illness.

Although an Example and a test example are given to the following and this invention is demonstrated in more detail, this invention is not limited only to these examples.

Example 1 3,4-methylenedioxy-6-adamantylphenol

1.38 g (1.0 eq) of sesamol and 1.52 g (1.0 eq) of adamantanol were added to 5 ml of trichloroacetic acid, and the temperature was warmed to about 40 ° C. and stirred for about 1 hour. 50 ml of methanol or water is added to the reaction solution after the reaction is completed, followed by stirring for about 30 minutes. After crystallization, the mixture was filtered and then dried in vacuo to yield 2.2 g of 3,4-methylenedioxy-6-adamantylphenol as a solid.

1 H-NMR (CDCl 3): δ (ppm) = 1.78 (6H), 2.07 (9H), 4.76 (s, 1H), 5.91 (s, 2H), 6.21 (s, 1H), 6.52 (s, 1H)

Test Example 1 Measurement of Antioxidant Effect Using HaCat Model

Human keratinocytes HaCat cell lines were aliquoted at 1.0 × 10 ⁶ per 60 mm dish and incubated for one day at 37 ° C., 5% CO ₂ conditions using DMEM (FBS 10%) medium with penicillin / streptomycin. Next, sesamol and the sesamol derivative of Example 1 were treated at a concentration of 10 ⁻⁴ mole, and tocopherol used as a positive control was also treated at the same concentration for 24 hours. The next day, after treatment with 4mM of t-BHT (t-butyl hydroperoxide) simultaneously with the above composition, cells were obtained after incubation for 4 hours at 37 ℃, 5% CO ₂ conditions. The cells were lysed by repeating the freezing / thawing process, and the following test was performed according to the method described in the assay kit.

That is, in the present invention, Calbiochem lipid peroxidation assay kit was used as a reagent, and ester peroxides associated with long-chain unsaturated fatty acids such as malonaldehyde and 4-hydroxy alkenal react with the reagent to form a stable compound at 586 nm. Lipid peroxidation was measured using. The results of the non-treated group as 100 are shown in Table 1 below.

compound MDE ^* Control 100 t-BHT 320 Tocopherol 270 Sesa Mall 250 Example 1 230 * MDE: Refers to malondialdehyde, a lipid peroxide product.

As can be seen in Table 1, the 3,4-methylenedioxy-6-adamantylphenol of Example 1 according to the present invention showed a superior lipid peroxidation inhibitory effect than tocopherol and sesamol used as a positive control Confirmed.

Test Example 2 Measurement of Antioxidant Effect by DPPH Method

Antioxidant effect was measured by the method according to Korean Patent Application No. 10-2002-0027050. Specifically, the measuring method is 1,1-diphenyl-2-picryl-hydrazyl (1,1-diphenyl-2-picryl-hydrazyl, DPPH) method, wherein the reagent is US Sigma (St. Louis, MO , USA). The reagent is used as a primary in vitro methods (in Vitro) In the process of determining the free-radical scavenging activity due to the presence of a relatively stable free radicals. Tocopherol, sesamol and Example 1, which are used for the measurement of DPPH free radical scavenging activity, and 96-well plates by concentrations of 500 μg / ml, 100 μg / ml, 20 μg / ml, 4 μg / ml and 0.8 μg / ml In each, and added DPPH made of 100M ethanol solution to make the total volume of solution 200µl. After leaving it at 37 ° C. for 30 minutes, absorbance was measured using a 520 nm ELISA reader. Free radical scavenging activity (%) was calculated by the following equation (1), and the concentration (IC 50) showing a radical scavenging ability of 50% was calculated. The results are shown in Table 2 below.

<Equation 1>

A: Absorbance of control wells without sample

B: Absorbance of Experimental Wells Treated with Samples

compound Radical scavenging ability (IC50) µg / ml Tocopherol - Sesa Mall 13.2 Example 1 10.2

As can be seen in Table 2, it was confirmed that the 3,4-methylenedioxy-6-adamantylphenol of Example 1 of the present invention showed an excellent radical scavenging effect than tocopherol and sesamol used as a positive control. .

Test Example 3 Discoloration Comparison Experiment

The sesamol and the sesamol derivative of Example 1 were dissolved in a vehicle (dimethylformaldehyde: ethanol: water = 5: 3: 2), and then visually observed for discoloration while being stored at 40 ° C. in a room temperature and evaluated based on the following criteria. It was. The results are shown in Table 3 below.

<Evaluation Criteria>

         ⊙ almost no discoloration

         O: discolored to pale yellow

         △: discolored to dark yellow

         X: discolored to dark brown

compound 30 days 60 days 90 days Sesa Mall △ X X Example 1 ⊙  O △

As can be seen in Table 3, the 3,4-methylenedioxy-6-adamantylphenol of Example 1 according to the present invention was confirmed to improve the problem of discoloration compared to sesamol.

Sesamol derivatives according to the present invention can be used in the external preparation composition for the skin, which is not particularly limited in the formulation. For example, supple cosmetics, astringent cosmetics, nourishing cosmetics, nourishing cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, powder, body lotion, body cream, body oil, body It may be formulated into a cosmetic composition such as an essence, a makeup base, a foundation, a hair dye, a shampoo, a rinse or a body cleanser, or a pharmaceutical composition such as an ointment, a gel, a cream, a patch or a spray. Each of these formulations may contain various bases and additives necessary and appropriate for the formulation of the formulation, and the types and amounts of these components can be easily selected by the inventors.

Formulation Example 1 Preparation of Nutritious Cosmetic Water (Milk Lotion)

Nutrients containing the sesamol derivatives prepared in Example 1 was prepared.

ingredient Content (% by weight) 1. Purified water To 100 2. Glycerin 8.0 3. Butylene Glycol 4.0 4. Hyaluronic Acid Extract 5.0 5. Beta Glucan 7.0 6. Carbomer 0.1 7. Sesamol Derivatives Quantity 8. Caprylic Capric Triglycerides 8.0 9. Squalane 5.0 10. Cetearyl Glucoside 1.5 11.Sorbitan Stearate 0.4 12. Cetearyl Alcohol 1.0 13. Preservative Quantity 14. Incense Quantity 15. Coloring Quantity 16. Triethanolamine 0.1

Formulation Example 2 Preparation of Nutritional Cream

Nutritional cream containing sesamol derivatives prepared in Example 1 was prepared.

ingredient Content (% by weight) 1. Purified water To 100 2. Glycerin 3.0 3. Butylene Glycol 3.0 4. Liquid paraffin 7.0 5. Beta Glucan 7.0 6. Carbomer 0.1 7. Sesamol Derivatives Quantity 8. Caprylic Capric Triglycerides 3.0 9. Squalane 5.0 10. Cetearyl Glucoside 1.5 11.Sorbitan Stearate 0.4 12. Polysorbate 1.2 13. Preservative Quantity 14. Incense Quantity 15. Coloring Quantity 16. Triethanolamine 0.1

Formulation Example 3 Preparation of Massage Cream

A massage cream containing sesamol derivatives prepared in Example 1 was prepared.

ingredient Content (% by weight) 1. Purified water To 100 2. Glycerin 8.0 3. Butylene Glycol 4.0 4. Liquid paraffin 45.0 5. Beta Glucan 7.0 6. Carbomer 0.1 7. Sesamol Derivatives Quantity 8. Caprylic Capric Triglycerides 3.0 9. Beeswax 4.0 10. Cetearyl Glucoside 1.5 11.Sesqui oleic acid sorbitan 0.9 12. Vaseline 3.0 13. Preservative Quantity 14. Incense Quantity 15. Coloring Quantity 16. Paraffin 1.5

Formulation Example 4 Preparation of Ointment

An ointment containing the sesamol derivatives prepared in Example 1 was prepared.

ingredient Content (% by weight) 1. Purified water To 100 2. Glycerin 8.0 3. Butylene Glycol 4.0 4. Liquid paraffin 15.0 5. Beta Glucan 7.0 6. Carbomer 0.1 7. Sesamol Derivatives Quantity 8. Caprylic Capric Triglycerides 3.0 9. Squalene 1.0 10. Cetearyl Glucoside 1.5 11.Sorbitan Stearate 0.4 12. Cetearyl Alcohol 1.0 13. Preservative Quantity 14. Incense Quantity 15. Coloring Quantity 16. Beeswax 4.0

As can be seen from the above, the sesamol derivative of the formula (1) provided by the present invention, by introducing the adamantane group directly into sesamol to increase the antioxidant effect and to improve the stability of the skin damaged by harmful free radicals It can be used for recovery and prevention, can prevent the aging of the biological membrane, can inhibit the production of peroxides of unsaturated fatty acids and derivatives thereof, it is possible to apply to other fields using the same.

Claims (6)

Sesamol derivative represented by the following formula (1). [Formula 1]

As a method for producing sesamol derivative of the general formula (1) represented by the following reaction formula 1, which is prepared by reacting sesamol and adamantanol at an equivalent ratio of 1: 1.0 to 1.3 in acidic conditions, and then recrystallized in a polar solvent. Scheme 1

[Formula 1]

 The acid is at least one selected from the group consisting of hydrochloric acid, nitric acid, sulfuric acid, p-toluenesulfonic acid, benzenesulfonic acid, acetic acid, trichloroacetic acid and trifluoroacetic acid, The polar solvent is a method for producing sesamol derivatives, characterized in that at least one selected from the group consisting of methanol, ethanol, isopropanol, acetone, acetonitrile and water. delete  According to claim 2, wherein the solvent used to react the sesamol and adamanthanol in an acid ratio of 1: 1.0 to 1.3 equivalent ratio of dichloromethane, tetrahydrofuran, ethyl acetate, acetonitrile, chloroform, ethyl ether, A method for producing sesamol derivatives, characterized in that at least one selected from the group consisting of trichloroethylene, benzene, and toluene. delete        A cosmetic composition comprising the sesamol derivative of claim 1.