KR101511279B1 - Derivatives of cyclohexandiol and cosmetic composition comprising the same - Google Patents

Abstract

(n=m+2 또는 n=m+3이고, m=1, 2 또는 3이며, R3, R4, R5 와 R6는 각각 독립적으로 수소 또는 C₁ 내지 C₁₀의 알킬기 또는 아실기이다.)The present invention relates to a derivative of a novel cyclohexanediol, a process for producing the same, and a whitening cosmetic composition containing the same. The novel cyclohexanediol derivative according to the present invention exhibits excellent whitening activity through inhibition of strong melanin formation, and thus is useful as a skin whitening cosmetic.

(for n = m + 2 or m + n = 3, and, m = 1, 2 or 3, R3, R4, R5 and R6 are independently hydrogen or C ₁ to C _10, respectively An alkyl group or an acyl group.

Description

[0001] The present invention relates to a cyclohexanediol derivative and a whitening cosmetic composition comprising the same,

The present invention relates to a novel cyclohexanediol derivative having excellent whitening activity through inhibition of melanin formation, a process for producing the same, and a whitening cosmetic composition containing the same.

Since ancient times, mankind has worshiped the sun and used it to treat anemia, rickets, tuberculosis, and skin diseases using sunlight. Some people enjoyed excessive sunbathing in the 20th century, believing that they made beautiful skin through suntan. However, in the late 1960s, overexposure to sunlight caused skin cancer and melanogenesis, leading to skin disorders that lead to pigmentation, such as spots and freckles. On the other hand, There has been a phenomenon. Skin blackening is a phenomenon in which melanin synthesized by melanocytes is transferred to keratinocytes, which are other skin cells, and these cells accumulate and accumulate through the keratinization process. Melanin has the ability to protect the skin, but excessive calm is causing cosmetic problems, especially for women. The synthesis of melanin in cells is very complex and controlled by various enzymes and substances. Among them, tyrosinase, a kind of polymerase that regulates the rate determining step, is the most important enzyme. Melanin is produced by rapid oxidation after tyrosine is decarboxylated naturally by tyrosinase through DOPA, dopaquinone, and dopachrome processes. Since melanin biosynthesis is an oxidation reaction, in the past, it was thought that melanin would be synthesized if only one enzyme of tyrosinase was found. However, as molecular biology developed, several genes similar to tyrosinase were found, which were called tyrosinase related proteins, Related protein-1 (TRP-1) and tyrosinase related protein-2 (TRP-2). TRP-1 and TRP-2 were found to be involved in decarboxylation and oxidation in dopachrome during melanin synthesis. It is known that melanin produced by this oxidation reaction is excessively deposited in the skin to form spots, freckles, black spots and the like, and seriously to skin cancer. In the treatment of such diseases, whitening cosmetics containing hydroquinone, kojic acid, arbutin, vitamin C and derivatives thereof, mulberry extract, oil soluble licorice extract, glucose acylated derivatives and the like have been developed . However, hydroquinone has been approved but has been limited in some medicines because of its irritation, and the use of kojic acid has been banned in 2003 due to the findings that it causes liver cancer. In addition, vitamin C and its derivatives are easily oxidized, and substances derived from natural extracts are more safe than synthetic substances, but their effects are insufficient, and glucose acylated derivatives have a very low synthesis efficiency. Korean Patent Laid-Open No. 10-2008-0004128 discloses a cyclic derivative compound in which a saturated or unsaturated linear or branched alkyl or acyl group is introduced into a hydroxyl group at 1 or 2 position by etherification or esterification reaction, It has been desired to develop a more safe and whitening compound.

Accordingly, the present inventors synthesized novel compound derivatives in order to reduce the pigmentation occurring on the skin as an active ingredient having high safety, such as a substance derived from a natural extract, and to develop an effective melanogenesis inhibitor even at a low concentration. Thereby confirming their excellent whitening effect, thereby completing the present invention.

Therefore, it is an object of the present invention to provide a novel cyclohexanediol derivative which is easy to manufacture, has excellent economic efficiency, is safe and has no whitening effect on skin, and has excellent whitening effect.

Another object of the present invention is to provide a process for preparing the novel cyclohexanediol derivative.

It is still another object of the present invention to provide a whitening cosmetic composition comprising the novel cyclohexanediol derivative.

In order to accomplish the above object, there is provided a cyclohexanediol derivative compound represented by the following formula (I) according to the present invention.

(I)

(I)

wherein A is an aliphatic cyclic compound having 6 carbon atoms and R1 and R2 are independently selected from the group consisting of a saturated or unsaturated straight or branched chain R3, R4, R5 and R6 are each independently selected from the group consisting of hydrogen, an alkyl group, an alkoxy group, an acyl group, a hydroxy group, an acyl group, a substituent selected from the group consisting of a hydroxyl group, a vinyl group, a nitrile group, a carboxyaldehyde group and an aldehyde group.

In formula (I), the bond of the oxygen atom connected to C m and C n respectively includes a cis or a trans bond.

In the above formula (I), R 1 and R 2 are preferably a saturated or unsaturated straight-chain or branched alkyl group or an acyl group which is a C ₂ to C ₁₂ saturated or unsaturated straight-chain or branched alkyl group or an acyl group.

R3, R4, R5 and R6 each independently may be selected from the group consisting of hydrogen, an alkyl group, an alkoxy group, an acyl group, a hydroxyl group, a vinyl group, a nitrile group, a carboxyaldehyde group and an aldehyde group, of ₁ to C ₁₀ An alkyl group or an acyl group.

According to another aspect of the present invention, there is provided a process for preparing a cyclohexanediol, comprising dissolving a cyclohexanediol of formula (II) in a solvent; Dissolving an alkyl halide or an acyl halide having 2 to 12 carbon atoms in a solvent and then adding the cyclohexanediol in an amount of 2.0 to 3.0 equivalents of the cyclohexanediol in the presence of a catalyst at a temperature of 10 to 35 ° C to effect etherification or esterification; And

Followed by separation and purification after completion of the reaction, to prepare a novel cyclohexanediol derivative.

(II)

(II)

(for n = m + 2 or m + n = 3, and, m = 1, 2 or 3, R3, R4, R5 and R6 are independently hydrogen or C ₁ to C _10, respectively An alkyl group or an acyl group.

Examples of the organic solvent used in the reaction include tetrahydrofuran, dichloromethane, 1,4-dioxane, diethyl ether, chloroform, and the like. It is most preferred to use dichloromethane, although it may be used.

As the catalyst, sodium hydrogen carbonate may be used in the etherification reaction, and triethylamine and 4-dimethylaminopyridine may be used in the esterification reaction.

According to another aspect of the present invention, there is provided a whitening cosmetic composition comprising the cyclohexanediol derivative compound represented by the formula (I) in an amount of 0.001 to 10 wt% based on the total weight of the cosmetic composition.

The novel cyclohexanediol derivative of the present invention is easy to manufacture and has excellent melanin formation inhibitory effect and pigment inhibition inhibitory effect even without skin irritation. Therefore, the novel cyclohexanediol derivative can be used for whitening skin which can prevent skin spots, freckles, It can be usefully used as a cosmetic composition.

Hereinafter, the present invention will be described in detail.

The novel cyclohexanediol derivative represented by the above formula (I) can be prepared by the following reaction scheme 1 and scheme 2.

The method for preparing a novel cyclohexanediol derivative represented by the above formula (I) is characterized in that a hydroxy group is bonded to an aliphatic cyclic compound having 6 carbon atoms at positions 1 and 3 (meta) or at positions 1 and 4 The compound of the ring structure at the para position is dissolved in an appropriate solvent and then one or two kinds of alkyl halides or acyl halides are dissolved in an appropriate solvent at a ratio of 2.0 to 3.0 equivalents of cyclohexanediol in an appropriate solvent, Or ester reaction. The organic solvent used in the reaction may be selected from tetrahydrofuran, dichloromethane, 1,4-dioxane, diethyl ether, chloroform, etc. Most preferably, dichloromethane is used.

Sodium hydrogen carbonate may be used as a catalyst in the etherification reaction of the following reaction formula (1). In the esterification reaction of the following reaction formula 2, triethylamine or 4-dimethylaminopyridine may be used as a catalyst.

In the following Reaction Scheme 1, C1 and C2 can be both 1 and 3 (meta) positions or 1 and 4 (para) positions, and R1 and R2 are saturated or unsaturated alkyl groups having 2 to 12 carbon atoms, Everything is possible. The reaction temperature is suitably 20 to 35 占 폚, preferably 25 to 30 占 폚. Unreacted materials remain at lower temperatures, while organic solvents used at temperatures above 35 ° C volatilize, making reaction difficult.

[Reaction Scheme 1]

In the following Reaction Scheme 2, C1 and C2 are both in positions 1 and 3 (meta) or in positions 1 and 4 (para), and R1 and R2 are saturated or unsaturated acyl groups having 2 to 12 carbon atoms, The reaction temperature is in the range of 10 to 15 ° C, and the reaction temperature after completion of addition of the acyl halide is preferably 25 to 30 ° C.

[Reaction Scheme 2]

As specific examples of the more preferable compounds obtained by the reaction formula 1 and the reaction formula 2 in the present invention, the cyclic compound A is derived from 1,3-cyclohexanediol, and R3, R4, R5 and R6 are hydrogen .

Specific examples of the 1,3-cyclohexanediol derivative include 1,3-diethoxycyclohexane, 1,3-dipropoxycyclohexane, 1,3-dibutoxycyclohexane, 1,3-bis (pentyloxy) (Octyloxy) cyclohexane, 1,3-bis (hexyloxy) cyclohexane, 1,3-bis (heptyloxy) cyclohexane, Cyclohexane, cyclohexane, 1,3-bis (decyloxy) cyclohexane, 1,3-bis (undecyloxy) cyclohexane, Cyclohexane, cyclohexane, 1,3-diisobutoxycyclohexane, 1,3-bis (3-methylbutoxy) cyclohexane, 1,3- (2-ethylbutoxy) cyclohexane, 1,3-bis (2-ethylbutyloxy) cyclohexane, Cyclohexane) cyclohexane, 1,3-bis (2-hexenyloxy) cyclohexane, 1,3-bis Cyclohexane, 1,3-bis (2-methylpentyloxy) cyclohexane, 1,3-bis (3-methyl- ) Cyclohexane, 1,3-bis (5-heptenyloxy) cyclohexane, 1,3-bis (4-pentenyloxy) cyclohexane, , 3-bis (5-hexenyloxy) cyclohexane, 1,3-bis (6-heptenyloxy) cyclohexane, 1-pentenyloxy) cyclohexane, 1,3-bis (7-octenyloxy) cyclohexane, 1,3-bis (9-decenyloxy) cyclohexane, Dimethyl-2,6-octadienyloxy) cyclohexane, 1,3-bis (10-undecenyloxy) cyclohexane, 1,3-bis (ethanoyloxy) cyclohexane, Cyclohexane) cyclohexane, 1,3-bis (butanoyloxy) cyclohexane, 1,3-bis (pentanoyloxy) (Heptanoyloxy) cyclohexane, 1,3-bis (octanoyloxy) cyclohexane, 1,3-bis- (nonanoyloxy) cyclohexane, 1,3-bis Cyclohexane) cyclohexane, 1,3-bis (undecanoyloxy) cyclohexane, 1,3-bis (dodecanoyloxy) cyclohexane, 1,3- , 1, 3-bis (2-butenoyloxy) cyclohexane, 1,3-bis (2-ethylbutanoyloxy) cyclohexane, Cyclohexane, 1,3-bis (2-methylpentanoyloxy) cyclohexane, 1,3-bis (2-methylbutanoyloxy) , 3-bis (2-methylbutanoyloxy) cyclohexane, 1,3-bis (2,2-dimethylpentanoyloxy) cyclohexane, , 1,3-bis (2,4-hexadienoyloxy) cyclohexane, 1,3-bis (2,4-pentadienoyloxy ) Cyclohexane, 1,3-bis (3-methyl-2-butenoyloxy) cyclohexane, 1,3-bis (2-methylheptanoyloxy) cyclohexane, (3-methylbutanoyloxy) cyclohexane, 1,3-bis (3-methylbutanoyloxy) cyclohexane, 1,3- Oxy) cyclohexane, 1,3-bis (3-methylpentanoyloxy) cyclohexane, 1,3-bis (4-methylhexanoyloxy) cyclohexane, Cyclohexane, 1,3-bis (5-oxohexanoyloxy) cyclohexane, 1,3-bis (6-oxoheptanoyloxy) cyclohexane, , 1,3-bis (3,5,5-trimethylhexanoyloxy) cyclohexane, and the like. Among these compounds, 1,3-bis (hexanoyloxy) cyclohexane, 1,3-bis (octanoyloxy) cyclohexane and 1,3-bis (decanoyloxy) cyclohexane have a more excellent inhibitory effect on melanin formation Respectively.

As another specific example, ring compound A is derived from 1,4-cyclohexanediol, and R3, R4, R5 and R6 are hydrogen.

Specific examples of the derivatives of 1,4-cyclohexanediol include 1,4-diethoxycyclohexane, 1,4-dipropoxycyclohexane, 1,4-dibutoxycyclohexane, 1,4-bis (pentyloxy Cyclohexane) cyclohexane, 1,4-bis (octyloxy) cyclohexane, 1,4-bis (hexyloxy) cyclohexane, ) Cyclohexane, 1,4-bis (dodecyloxy) cyclohexane, 1,4-bis (undecyloxy) cyclohexane, 1,4- 1,4-bis (3-methylbutoxy) cyclohexane, 1,4-bis (2,3-dimethylbutoxy) cyclohexane, 1,4-diisobutoxycyclohexane, Bis (2-ethylbutyloxy) cyclohexane, 1,4-bis (2-ethylbutoxy) cyclohexane, 1,4- Heptenyloxy) cyclohexane, 1,4-bis (2-hexenyloxy) cyclohexane, 1,4-bis Butene) cyclohexane, 1,4-bis (2-methylpentyloxy) cyclohexane, 1,4-bis (5-heptenyloxy) cyclohexane, 1,4-bis (4-pentenyloxy) cyclohexane, 1,4-bis (5-heptenyloxy) cyclohexane, Cyclohexane, 1,4-bis (5-hexenyloxy) cyclohexane, 1,4-bis (6-heptenyloxy) cyclohexane, 1,4- 1-pentenyloxy) cyclohexane, 1,4-bis (7-octenyloxy) cyclohexane, 1,4-bis (9-decenyloxy) cyclohexane, 1,4- (Dimethyl-2,6-octadienyloxy) cyclohexane, 1,4-bis (10-undecenyloxy) cyclohexane, 1,4-bis (ethanoyloxy) cyclohexane, Bis (pentanoyloxy) cyclohexane, 1,4-bis (butanoyloxy) cyclohexane, 1,4-bis (Heptanoyloxyl) cyclohexane, 1,4-bis (octanoyloxyl) cyclohexane, 1,4-bis- (nonanoyloxyl) cyclohexane, 1,4-bis Decanoyloxy) cyclohexane, 1,4-bis (undecanoyloxy) cyclohexane, 1,4-bis (dodecanoyloxy) cyclohexane, 1,4- (2-methylbutanoyloxy) cyclohexane, 1,4-bis (2-buthonyloxy) cyclohexane, 1,4-bis Bis (2-methylpentanoyloxy) cyclohexane, 1,4-bis (2-methylbutenoyloxy) cyclohexane, 1,4- (2,4-hexadienoyloxy) cyclohexane, 1,4-bis (2,2-dimethylpentanoyloxy) cyclohexane, 1,4-bis Hexane, 1,4-bis (2,4-hexadienoyloxy) cyclohexane, 1,4-bis (2,4-pentadienoyl Bis (2-methylheptanoyloxy) cyclohexane, 1,4-bis (2-methylheptanoyloxy) cyclohexane, Bis (3-methylbutanoyloxy) cyclohexane, 1,4-bis (3-methylbutanoyl) cyclohexane, (4-methylpentanoyloxy) cyclohexane, 1,4-bis (4-methylpentanoyloxy) cyclohexane, 1,4-bis ) Cyclohexane, 1,4-bis (5-oxohexanoyloxy) cyclohexane, 1,4-bis (6-oxoheptanoyloxy) Hexane, 1,4-bis (3,5,5-trimethylhexanoyloxy) cyclohexane, and the like. Among these compounds, 1,4-bis (butanoyloxy) cyclohexane, 1,4-bis (octanoyloxy) cyclohexane, 1,4-bis (decanoyloxy) cyclohexane, 1,4- - ethylhexanoyloxy) cyclohexane showed more excellent melanin formation inhibitory effect.

The thus synthesized 1,3-cyclohexanediol or 1,4-cyclohexanediol derivative of the formula (I) of the present invention is mixed with a commonly used cosmetic carrier to produce cosmetic cream, softening longevity, essence, cosmetic pack and nutrition Cosmetics such as lotion and the like, or ointment for external skin is manufactured.

As the cosmetic carrier, diethyl sebacate, stearic acid, glycerin and the like commonly used can be used, but the present invention is not limited thereto. The content of the cyclohexanediol derivative in the cosmetic composition or the ointment for skin is preferably 0.001 to 10% by weight. If the content is less than 0.001% by weight, the whitening effect of the skin is not sufficiently exhibited. If the content is more than 10% by weight, Not only does the skin whitening effect increase due to the use of the click derivative, but also reduces the other cosmetic effects of the cosmetic.

Hereinafter, the present invention will be described in detail with reference to the following examples and test examples. However, these examples are provided to aid understanding of the present invention, and the present invention is not limited thereto.

[Example]

Example 1: Preparation of 1,3-bis (propanoyloxy) cyclohexane

5 g (43 mmol) of 1,3-cyclohexanediol and 80 ml of dichloromethane were added to a one-necked round bottom flask (250 ml), and the mixture was cooled to 10 ° C. using ice bath. 10 g (99 mmol) of triethylamine A mixture of 10.55 g (99 mmol) of propanoyl chloride and 100 ml of dichloromethane was slowly added dropwise. After completion of the dropwise addition, the ice bath was removed, and the mixture was stirred at room temperature for 6 hours. The reaction mixture was filtered and washed three times with 5% brine. The organic layer was dehydrated using anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and purified by silica gel column chromatography to obtain 10.3 g (yield: 93.4%) of 1,3-bis (propanoyloxy) cyclohexane.

_{^{1 H-NMR (CDCl 3)}} : δ 1.11 (t, 6H), 1.39~1.48 (m, 2H), 1.53~2.05 (m, 8H), 2.05 (q, 4H), 3.88 (m, 2H)

Example 2: Preparation of 1,3-bis (butanoyloxy) cyclohexane

(Butanolyloxy) cyclohexane (yield: 92.7%) was obtained in the same manner as in Example 1, except that butyryl chloride was used in place of propanoyl chloride.

¹ H-NMR (CDCl ₃ ):? 0.98 (t, 6H), 1.40-2.01 (m, 8H)

Example 3: Preparation of 1,3-bis (hexanoyloxy) cyclohexane

12.3 g (yield: 91.6%) of 1,3-bis (hexanoyloxy) cyclohexane was obtained in the same manner as in Example 1, except that hexanoyl chloride was used in place of propanoyl chloride.

¹ H-NMR (CDCl ₃ ):? 0.93 (t, 6H), 1.25-1.30 (m, 8H), 1.66 (m, 4H), 1.30-1.52 (m 2H), 1.52-2.02 2.26 (t, 4H), 3.75-3.94 (m, 2H)

Example 4: Preparation of 1,3-bis (octanoyloxy) cyclohexane

(Octanoyloxy) cyclohexane (yield: 87.4%) was obtained in the same manner as in Example 1, except that octanoyl chloride was used in place of propanoyl chloride.

¹ H-NMR (CDCl ₃ ):? 0.96 (t, 6H), 1.28-1.31 (m, 12H), 1.34 (m, 4H), 1.38-1.48 , 2.29 (t, 4 H), 3.95 (m, 2 H)

Example 5: Preparation of 1,3-bis (decanoyloxy) cyclohexane

(Decanoyloxy) cyclohexane (yield: 93.6%) was obtained in the same manner as in Example 1, except that decanoyl chloride was used in place of propanoyl chloride.

¹ H-NMR (CDCl ₃ ):? 0.92 (t, 6H), 1.28 (s, 20H), 1.34 (m, 4H), 1.38-1.46 (t, 4 H), 3.95 (m, 2 H)

Example 6: Preparation of 1,3-bis (2-methylbutanoyloxy) cyclohexane

(Yield: 94.9%) of 1,3-bis (2-methylbutanoyloxy) cyclohexane was prepared in the same manner as in Example 1, except that 2-methylbutanoyl chloride was used in place of propanoyl chloride. ≪ / RTI >

¹ H-NMR (CDCl ₃ ):? 1.01 (t, 6H), 1.28 (d, 6H), 1.40-1.47 (m, 2H), 1.54-2.07 (m, 2H)

Example 7: Preparation of 1,3-bis (2-methylpentanoyloxy) cyclohexane

(2-methylpentanoyloxy) cyclohexane The title compound was prepared in the same manner as in Example 1, except that 2-methylpentanoyl chloride was used instead of 2-methylpentanoyl chloride to give 1,3-bis 11.9 g (yield: 88.6%) was obtained.

¹ H-NMR (CDCl ₃ ):? 0.98 (t, 6H), 1.28 (d, 6H), 1.34 (m, 4H), 1.41-2.11 , 2H)

Example 8: Preparation of 1,3-bis (2-methylhexanoyloxy) cyclohexane

(Yield: 90.2%) of 1,3-bis (2-methylhexanoyloxy) cyclohexane was prepared in the same manner as in Example 1, except that 2-methylhexanoyl chloride was used in place of propanoyl chloride. ≪ / RTI >

¹ H-NMR (CDCl ₃ ):? 1.01 (t, 6H), 1.28 (d, 6H), 1.36 (m, 4H) (m, 10H), 2.52 (m, 2H), 3.95 (m, 2H)

Example 9: Preparation of 1,3-bis (2-methylheptanoyloxy) cyclohexane

(Yield: 87.7%) of 1,3-bis (2-methylheptanoyloxy) cyclohexane was prepared in the same manner as in Example 1, except that 2-methylheptanoyl chloride was used in place of propanoyl chloride. ≪ / RTI >

¹ H-NMR (CDCl ₃ ):? 1.02 (t, 6H), 1.28 (d, 6H), 1.33 (m, 8H) (m, 10H), 2.53 (m, 2H), 4.04 (m, 2H)

Example 10: Preparation of 1,3-bis (2-ethylhexanoyloxy) cyclohexane

14.3 g (yield: 90.2%) of 1,3-bis (2-ethylhexanoyloxy) cyclohexane was prepared in the same manner as in Example 1 except that 2-ethylhexanoyl chloride was used in place of propanoyl chloride. ≪ / RTI >

_{^{1 H-NMR (CDCl 3)}} : δ 0.99 (t, 12H), 1.31 (m, 4H), 1.34 (m, 4H), 1.38~1.48 (m, 2H), 1.56~2.09 (m, 14H), 2.36 (m, 2 H), 3.96 (m, 2 H)

Example 11: Preparation of 1,3-bis (2-methyl-4-pentenoyloxy) cyclohexane

(2-methyl-4-pentenoyloxy) cyclohexane was prepared in the same manner as in Example 1, except that 2-methyl-4-pentenoyl chloride was used in place of propanoyl chloride. 11.7 g (yield: 88.2%) was obtained.

_{^{1 H-NMR (CDCl 3)}} : δ 1.28 (d, 6H), 1.41~1.52 (m, 2H), 1.59~2.10 (m, 6H), 2.21~2.43 (m, 4H), 2.57 (m, 2H) , 3.95 (m, 2H), 4.95-5.05 (m, 4H), 5.71-5.75 (m, 2H)

Example 12: Preparation of 1,4-bis (propanoyloxy) cyclohexane

5 g (43 mmol) of 1,4-cyclohexanediol and 80 ml of dichloromethane were added to a one-necked round bottom flask (250 ml), and the mixture was cooled to 10 ° C using ice bath. 10 g (99 mmol) of triethylamine A mixture of 10.55 g (99 mmol) of propanoyl chloride and 100 ml of dichloromethane was slowly added dropwise. After completion of the dropwise addition, the ice bath was removed, and the mixture was stirred at room temperature for 6 hours. The reaction mixture was filtered and washed three times with 5% brine. The organic layer was dehydrated using anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain 9.3 g (yield: 94.7%) of 1,4-bis (propanoyloxy) cyclohexane.

¹ H-NMR (CDCl ₃ ):? 1.16 (t, 6H), 1.51-1.76 (m, 8H)

Example 13: Preparation of 1,4-bis (butanoyloxy) cyclohexane

(Butanoyloxy) cyclohexane (yield: 91.6%) was obtained in the same manner as in Example 12 except that butyryl chloride was used in place of propanoyl chloride.

¹ H-NMR (CDCl ₃ ):? 1.0 (t, 6H), 1.48-1.77 (m, 12H)

Example 14: Preparation of 1,4-bis (hexanoyloxy) cyclohexane

(Hexanoyloxy) cyclohexane (yield: 94.5%) was obtained in the same manner as in Example 12, except that hexanoyl chloride was used in place of propanoyl chloride.

_{^{1 H-NMR (CDCl 3)}} : δ 1.10 (t, 6H), 1.27~1.35 (m, 8H), 1.19~1.86 (m, 8H), 2.33 (t, 4H), 4.01 (m, 2H)

Example 15: Preparation of 1,4-bis (octanoyloxy) cyclohexane

(Octanoyloxy) cyclohexane (yield: 85.1%) was obtained in the same manner as in Example 12, except that octanoyl chloride was used in place of propanoyl chloride.

¹ H-NMR (CDCl ₃ ):? 1.09 (t, 6H), 1.29-1.34 (m, 12H), 1.61 (m, 4H), 1.64-1.88 (m, 2H)

Example 16: Preparation of 1,4-bis (decanoyloxy) cyclohexane

(Decanoyloxy) cyclohexane (yield: 89.8%) was obtained in the same manner as in Example 12, except that decanoyl chloride was used in place of propanoyl chloride.

¹ H-NMR (CDCl ₃ ):? 1.06 (t, 6H), 1.36 (s, 20H), 1.39 (m, 4H), 1.64-1.88 , 2H)

Example 17: Preparation of 1,4-bis (2-methylbutanoyloxy) cyclohexane

(Yield: 93.2%) of 1,4-bis (2-methylbutanoyloxy) cyclohexane was prepared in the same manner as in Example 12, except that 2-methylbutanoyl chloride was used in place of propanoyl chloride. ≪ / RTI >

_{^{1 H-NMR (CDCl 3)}} : δ 1.05 (t, 6H), 1.25 (d, 6H), 1.62~1.84 (m, 8H), 2.51 (m, 2H), 3.97 (m, 2H)

Example 18: Preparation of 1,4-bis (2-methylpentanoyloxy) cyclohexane

(Yield: 90.1%) of 1,4-bis (2-methylpentanoyloxy) cyclohexane was obtained in the same manner as in Example 12 except that 2-methylpentanoyl chloride was used instead of 2- ≪ / RTI >

_{^{1 H-NMR (CDCl 3)}} : δ 1.03 (t, 6H), 1.22~1.30 (m, 10H), 1.53~1.77 (m, 12H), 2.38 (m, 2H), 3.40 (m, 2H)

Example 19: Preparation of 1,4-bis (2-methylhexanoyloxy) cyclohexane

(Yield: 90.8%) of 1,4-bis (2-methylhexanoyloxy) cyclohexane was prepared in the same manner as in Example 12, except that 2-methylhexanoyl chloride was used instead of 2- ≪ / RTI >

_{^{1 H-NMR (CDCl 3)}} : δ 1.04 (t, 6H), 1.20~1.34 (m, 12H), 1.48~1.88 (m, 12H), 2.51 (m, 2H), 3.98 (m, 2H)

Example 20: Preparation of 1,4-bis (2-methylheptanoyloxy) cyclohexane

(Yield: 89%) of 1,4-bis (2-methylheptanoyloxy) cyclohexane was prepared in the same manner as in Example 12 except that 2-methylheptanoyl chloride was used instead of 2- ≪ / RTI >

¹ H-NMR (CDCl ₃ ):? 1.05 (t, 6H), 1.34 (m, 8H), 1.32 (m, 4H), 1.57-1.83 , 2H)

Example 21: Preparation of 1,4-bis (2-ethylhexanoyloxy) cyclohexane

14.6 g (yield: 92.1%) of 1,4-bis (2-ethylhexanoyloxy) cyclohexane was prepared in the same manner as in Example 12 except that 2-ethylhexanoyl chloride was used in place of propanoyl chloride. ≪ / RTI >

¹ H-NMR (CDCl ₃ ):? 1.0 (t, 12H), 1.25-1.35 (m, 8H), 1.52-1.79

Example 22: Preparation of 1,4-bis (2-methyl-4-pentenoyloxy) cyclohexane

Prepared by the same method as in Example 12 except that 2-methyl-4-pentenoyl chloride was used in place of propanoyl chloride, to give 12.4 g of 1,4-bis (2-methyl-4-pentenoyloxy) cyclohexane (Yield: 93.5%).

¹ H-NMR (CDCl ₃ ):? 1.16 (d, 6H), 1.53-1.77 (m, 8H), 2.24-2.63 (m, 6H), 3.92 , 5.83 (m, 2 H)

Test Example 1: Melanin production inhibition test

Compounds prepared in accordance with the methods described in Examples 1 to 22 above and 1,2-cyclohexane-based compounds as comparative examples, and beta arbutin, niacinamide, and hydroquinone in rat melanoma cells B- 16) to study the whitening effect at the cellular level. The thus prepared compounds were added to the culture medium of B-16 melanoma cells so as to have a final concentration of 50 ug / mL. After culturing for 24 hours, adherent and growing cells were treated with trypsin-EDTA solution, And then the resulting melanin was extracted. The amount of melanin was determined by measuring the absorbance at 400 nm using a spectrophotometer after cooling to room temperature and boiling the melanin for 10 minutes by adding 1 mL of 1 N NaOH solution to the extract. 10 ⁴ cells). Melanin production relative to the control group was calculated as the inhibition rate, and the results are shown in Table 1 below.

Test substance Material name Melanin synthesis inhibition (%) Example 1 1,3-bis (propanoyloxy) cyclohexane 42.39 Example 2 1,3-bis (butanoyloxy) cyclohexane 59.42 Example 3 1,3-bis (hexanoyloxy) cyclohexane 63.90 Example 4 1,3-Bis (octanoyloxy) cyclohexane 70.11 Example 5 1,3-Bis (decanoyloxy) cyclohexane 72.78 Example 6 1,3-bis (2-methylbutanoyloxy) cyclohexane 49.67 Example 7 1,3-bis (2-methylpentanoyloxy) cyclohexane 58.15 Example 8 1,3-bis (2-methylhexanoyloxy) cyclohexane 48.31 Example 9 1,3-bis (2-methylheptanoyloxy) cyclohexane 54.84 Example 10 1,3-bis (2-ethylhexanoyloxy) cyclohexane 50.41 Example 11 1,3-bis (2-methyl-4-pentenoyloxy) cyclohexane 43.92 Example 12 1,4-bis (propanoyloxy) cyclohexane 30.93 Example 13 1,4-bis (butanoyloxy) cyclohexane 54.38 Example 14 1,4-bis (hexanoyloxy) cyclohexane 37.45 Example 15 1,4-bis (octanoyloxy) cyclohexane 51.11 Example 16 1,4-bis (decanoyloxy) cyclohexane 55.38 Example 17 1,4-bis (2-methylbutanoyloxy) cyclohexane 35.50 Example 18 1,4-bis (2-methylpentanoyloxy) cyclohexane 27.31 Example 19 1,4-bis (2-methylhexanoyloxy) cyclohexane 41.63 Example 20 1,4-bis (2-methylheptanoyloxy) cyclohexane 39.08 Example 21 1,4-bis (2-ethylhexanoyloxy) cyclohexane 37.02 Example 22 1,4-bis (2-methyl-4-pentenoyloxy) cyclohexane 33.71 Comparative Example 1 1,2-bis (propanoyloxy) cyclohexane 15.27 Comparative Example 2 1,2-bis (butanoyloxy) cyclohexane 20.55 Comparative Example 3 1,2-bis (hexanoyloxy) cyclohexane 18.97 Comparative Example 4 1,2-bis (octanoyloxy) cyclohexane 28.58 Comparative Example 5 1,2-bis (decanoyloxyl) cyclohexane 30.24 Comparative Example 6 1,2-bis (2-methylbutanoyloxy) cyclohexane 16.47 Comparative Example 7 1,2-bis (2-methylpentanoyloxy) cyclohexane 13.57 Comparative Example 8 1,2-bis (2-methylhexanoyloxy) cyclohexane 20.58 Comparative Example 9 1,2-bis (2-methylheptanoyloxy) cyclohexane 11.08 Comparative Example 10 1,2-bis (2-ethylhexanoyloxy) cyclohexane 4.86 Comparative Example 11 1,2-bis (2-methyl-4-pentenoyloxy) cyclohexane 9.85 Comparative Example 12 Beta arbutin 1.6 Comparative Example 13 Niacinamide < / RTI > 11.99 Comparative Example 14 Hydroquinone - (death)

All of the compounds of the above examples showed equivalent or better melanin formation inhibitory effects to melanoma cells of cultured rats compared with beta arbutin, niacinamide. In particular, hydroquinone killed all of the melanoma cells in the rat with a cytotoxicity at a concentration of 50 ug / mL, but the compounds do not show cytotoxicity even at a concentration of 50 ug / mL and thus have a melanin formation inhibitory effect superior to hydroquinone . Comparing the 1,2-cyclohexanediol derivatives of the compounds of Comparative Examples 1 to 11 with the inhibitory effects of melanin formation, it was found that 1,3-cyclohexanediol and 1,4-cyclohexanediol derivatives, The inhibitory effect was excellent. Cyclohexanediol derivative compound is superior to the 1,2-cyclohexanediol derivative compound in the effect of inhibiting the melanin formation of the 1,4-cyclohexanediol derivative compound and is superior to 1,4-cyclohexanediol derivative compound in melanin production of the 1,3-cyclohexanediol derivative compound The inhibitory effect was excellent. In particular, the compounds of Examples 3, 4, and 5 relating to the 1,3-cyclohexanediol derivative exhibited remarkably excellent melanin formation inhibitory effect.

Production Examples 1 to 3: Production of softening longevity

The softening longevity was calculated from the composition shown in Table 2 below.

Composition Formulation 1 (% by weight) compare
Production Example 1 Production Example 1 Production Example 2 Production Example 3 1,3-bis (hexanoyloxy) cyclohexane 0.10 - - - 1,3-Bis (octanoyloxy) cyclohexane - 0.10 - - 1,3-Bis (decanoyloxy) cyclohexane - - 0.10 - ethanol 10.00 10.00 10.00 10.00 PIGGY-60 Hydrogenated Castor Oil 0.50 0.50 0.50 0.50 Methylparaben 0.20 0.20 0.20 0.20 glycerin 5.00 5.00 5.00 5.00 Butylene glycol 3.00 3.00 3.00 3.00 incense Suitable amount Suitable amount Suitable amount Suitable amount Purified water to 100 to 100 to 100 to 100

Production Examples 4 to 6: Production of emulsion

An emulsion was prepared with the composition shown in Table 3 below.

Composition
Formulation 2 (% by weight) compare
Production Example 2 Production Example 4 Production Example 5 Production Example 6 1,3-bis (hexanoyloxy) cyclohexane 0.10 - - - 1,3-Bis (octanoyloxy) cyclohexane - 0.10 - - 1,3-Bis (decanoyloxy) cyclohexane - - 0.10 - Propylene glycol 10.00 10.00 10.00 10.00 glycerin 5.00 5.00 5.00 5.00 Butylene glycol 5.00 5.00 5.00 5.00 Cetearyl Olivate / Sorbitan Olivate 3.00 3.00 3.00 3.00 Caprylic / capric triglyceride 10.00 10.00 10.00 10.00 Carbomer 0.30 0.30 0.30 0.30 Triethanolamine 0.30 0.30 0.30 0.30 Propylparaben 0.05 0.05 0.05 0.05 Methylparaben 0.15 0.15 0.15 0.15 incense Suitable amount Suitable amount Suitable amount Suitable amount Purified water to 100 to 100 to 100 to 100

Production Examples 7 to 9: Preparation of cream

Creams were prepared with the compositions shown in Table 4 below.

Composition Formulation 3 (% by weight) compare
Production Example 3 Production Example 7 Production Example 8 Production Example 9 1,3-bis (hexanoyloxy) cyclohexane 0.10 - - - 1,3-Bis (octanoyloxy) cyclohexane - 0.10 - - 1,3-Bis (decanoyloxy) cyclohexane - - 0.10 - Propylene glycol 10.00 10.00 10.00 10.00 glycerin 8.00 8.00 8.00 8.00 Betaine 1.00 1.00 1.00 1.00 Butylene glycol 5.00 5.00 5.00 5.00 Polyglyceryl-3 methyl glucoside distearate 2.00 2.00 2.00 2.00 Caprylic / capric triglyceride 10.00 10.00 10.00 10.00 Cetanol 1.00 1.00 1.00 1.00 Mineral oil 5.00 5.00 5.00 5.00 Carbomer 0.50 0.50 0.50 0.50 Triethanolamine 0.50 0.50 0.50 0.50 Propylparaben 0.05 0.05 0.05 0.05 Butyl paraben 0.05 0.05 0.05 0.05 Methylparaben 0.20 0.20 0.20 0.20 incense Suitable amount Suitable amount Suitable amount Suitable amount Purified water to 100 to 100 to 100 to 100

Test Example 2: Confirmation of inhibition of pigmentation

Experiments were carried out in the following manner in order to verify the inhibitory effects of the pigment formation by Production Examples 1 to 9 and Comparative Production Examples 1 to 3 described above.

A total of 45 healthy subjects were irradiated with light of 60 mJ / cm ² using an artificial solar irradiator at a distance of 10 cm from the arm. Before irradiation, the irradiated portions were washed well with an aqueous solution of 70% ethanol, and the compositions of Production Examples 1 to 9 and Comparative Production Examples 1 to 3 were applied twice a day from 3 days before irradiation until 8 weeks after irradiation.

The inhibition effect of pigmentation was measured by using a colorimeter (SPECTROPHOTOMETER CM-3500d, KONICA MINOLTA, JAPAN) at intervals of 2 weeks after the irradiation of the sunlight immediately before and after the application of the formulations. .

Experimental material L value Early 4 weeks 8 weeks Comparative Preparation Example 1 58.42 + - 0.95 59.99 + - 0.53 61.62 ± 0.38 Formulation 1 Production Example 1 57.44 + 0.92 62.51 + - 0.17 66.21 + - 0.27 Production Example 2 58.09 + - 0.85 62.36 + - 0.23 66.72 ± 0.69 Production Example 3 58.58 ± 0.91 60.17 + - 0.72 63.13 + - 0.52 Comparative Production Example 2 58.66 ± 1.32 59.72 ± 0.18 62.55 + - 1.05 Formulation 2 Production Example 4 57.16 + - 1.23 61.65 ± 0.37 66.19 + - 0.85 Production Example 5 58.35 + - 1.11 63.76 ± 0.64 68.03 + - 0.92 Production Example 6 57.55 +/- 1.65 61.68 ± 0.06 66.54 0.35 Comparative Production Example 3 58.12 ± 1.02 59.38 ± 0.56 61.84 + - 0.42 Formulation 3 Production Example 7 57.66 + - 1.64 61.81 + - 0.10 67.98 + - 0.52 Production Example 8 58.01 + - 1.79 62.99 + - 0.14 69.70 + - 0.61 Production Example 9 58.36 ± 1.88 62.07 ± 0.12 67.29 + - 0.86

As shown in the above table, the cosmetics of Production Examples 1 to 9 containing the substances of the present invention showed a superior skin whitening effect as compared with the cosmetics of Comparative Production Examples 1 to 3.

Test Example  3: Skin irritation test

The skin irritation tests according to Preparation Examples 1 to 9 and Comparative Preparation Examples 1 to 3 were carried out in the same manner as in Test Example 2. The degree of stimulation was visually evaluated, and the results are shown in Table 6 below.

Tester Formulation 1 Comparative Preparation Example 1
Formulation 2 Comparative Production Example 2
Formulation 3 Comparative Production Example 3
Production Example 1 Production Example 2 Production Example 3 Production Example 4 Production Example 5 Production Example 6 Production Example 7 Production Example 8 Production Example 9 One 0 0 0 0 0 0 One One One One One One 2 0 0 One One 0 0 One One One One One 2 3 0 0 0 0 0 0 0 0 0 0 0 0 4 One One 2 2 One One 2 One 2 2 2 3 5 One 0 2 2 One 0 2 2 One 2 3 3 6 0 0 0 0 0 0 One One One One 2 3 7 0 One One One 0 One One 2 One 2 2 2 8 0 0 0 0 0 0 0 0 0 0 0 One 9 0 0 One One 0 0 One 2 One One 2 3 10 0 0 0 0 0 0 0 One 0 One One 2 11 0 0 0 0 0 0 0 0 0 0 0 0 12 One One One One One One One 2 One 2 2 2 13 0 One One 2 One One One 2 One One 2 2 14 0 0 0 One 0 0 One 2 0 One 2 2 15 0 0 0 One 0 0 0 One 0 0 0 One Average 0.20 0.27 0.60 0.80 0.27 0.27 0.80 1.20 0.67 1.00 1.33 1.80

Degree of stimulation (0: No stimulation ~ 5: Disused by stimulation)

As shown in the above table, the cosmetics of Production Examples 1 to 9 containing the substances of the present invention were found to have less skin irritation than the cosmetics of Comparative Production Examples 1 to 3.

Claims (8)

1. A skin whitening cyclohexanediol derivative represented by the following formula (I), wherein the derivative is 1,3-bis (hexanoyloxy) cyclohexane, 1,3-bis (octanoyloxy) 3-bis (decanoyloxy) cyclohexane. ≪ / RTI >

(I)
[Cm is the cyclic structure at Cn and the 1 and 3 (meta) positions, R1 and R2 are C ₃ to C ₁₀ acyl, and R 3, R 4, R 5 and R 6 are hydrogen .] delete delete delete delete delete delete A cyclohexanediol derivative represented by the following formula (I), wherein the derivative is 1,3-bis (hexanoyloxy) cyclohexane, 1,3-bis (octanoyloxy) cyclohexane or 1,3- Decanoyloxy) cyclohexane, wherein the skin-whitening cyclohexanediol derivative compound is contained in an amount of 0.001 to 10% by weight based on the total weight of the cosmetic composition.

(I)
[Cm is the cyclic structure at Cn and the 1 and 3 (meta) positions, R1 and R2 are C ₃ to C ₁₀ acyl, and R 3, R 4, R 5 and R 6 are hydrogen .]