JP2000109473A - New flavan derivative, its production and cosmetic containing the derivative as active ingredient - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new flavan derivative having excellent pigmentation- inhibiting effect, excellent beautifully whitening effect, high skin safety and storage stability and useful as an active ingredient for cosmetics. SOLUTION: A compound of formula I (R1 to R3 are each H, a 1-20C alkyl, an alkenyl or the like), preferably 2-(2,4-dihydroxyphenyl)-7-hydroxychroman. The compound of formula I is obtained by catalytically hydrogenating a hydrochalcone derivative of formula II (R4 to R7 are each H, a 1-20C alkyl, an alkenyl or the like) [for example, 1,3-bis(2,4-dibenzyloxyphenyl)-3-hydroxy-1- propene] in a solvent such as methanol usually at 0-100 deg.C under the atmospheric pressure to 1 MPa.G, for example, by a method for bringing the compound of formula II into contact with hydrogen in the presence of a catalyst such as Pd/C, and subsequently removing protecting groups.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel flavan derivative expected as an antioxidant, an ultraviolet absorber, a whitening agent, etc., a method for producing the same, and skin safety containing the flavan derivative as an active ingredient. The present invention relates to a cosmetic having excellent storage stability, and an excellent pigmentation inhibiting effect and whitening effect.

[0002]

2. Description of the Related Art The skin is inflamed mainly by erythema due to sunlight, particularly ultraviolet rays, and various chemical mediators are released to stimulate melanocytes. This promotes melanin synthesis, changes the skin tone, and turns black.
This darkening is due to overproduction of melanin, which is produced in melanocytes and passed to epidermal cells.

[0003] Conventionally, vitamin C has been used to prevent skin pigmentation, spots, freckles, etc., and to maintain original white skin.
Whitening cosmetics containing salts of (ascorbic acid) and various derivatives, hydroquinone monobenzyl ether, hydrogen peroxide and the like have been proposed. In addition, those using various plant extracts, plant-derived gallic acid, geraniin, and the like have been proposed. Furthermore, it has been reported that hydroquinone or hydrochalcone derivatives such as florin, phlorizin, phlorezin (JP-A-4-235112) and dihydrophloretin (WO95 / 11662) have a melanin production inhibitory effect. However, these are often insufficient in storage stability in the preparation or inferior in the effect of suppressing inflammation caused by ultraviolet rays, so that the pigmentation suppressing effect and the whitening effect are not sufficiently recognized. In addition, when hydroquinone monobenzyl ether or the like is mixed in the cosmetic, it has a lightening effect on the pigmented skin, but has problems in skin safety such as allergy and skin irritation. Furthermore, various plant extracts have the problem that the effect is insufficient or the quality is not constant.

[0004] US Patent No. 4,954,659 reports that a hydrochalcone derivative has an antioxidant effect, but does not disclose its usefulness as a cosmetic. Further, JP-A-5-213729 reports that a dihydrochalcone derivative has an excellent melanin-suppressing effect, but the effect is not sufficient. JP-A-9-221439 discloses a hydrochalcone derivative exhibiting a high whitening effect. However, in the method of obtaining the same, the quality is not constant by the plant extraction method, and severe conditions are required for chemical synthesis. However, there are problems such as difficulty in establishing an industrial production method.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to develop a cosmetic which is excellent in the effect of inhibiting pigmentation and whitening, has high skin safety and is excellent in storage stability.

[0006]

Means for Solving the Problems Accordingly, the present inventors have:
As a result of intensive studies in view of the above problems, high tyrosinase activity inhibition is observed in specific flavan derivatives, and high skin safety, and excellent storage stability even when blended in various cosmetics. Have found that they have excellent ultraviolet absorbing ability and can be easily manufactured industrially, and have completed the present invention.

That is, the present invention relates to: General formula (1)

[0008]

Embedded image (Wherein R ^{1 to} R ³ are each independently a hydrogen atom,
Represents up to 20 linear or branched alkyl, alkenyl, and acyl groups, and an optionally substituted benzyl group. )

A novel flavan derivative represented by the formula: Equation (2)

[0010]

Embedded image

[0011] 2- (2,4-dihydroxyphenyl) -7 represented by
-Hydroxy chroman,. General formula (3)

[0012]

Embedded image (Wherein R ^{4 to} R ⁷ are each independently a hydrogen atom,
Represents up to 20 linear or branched alkyl, alkenyl, and acyl groups, and an optionally substituted benzyl group. )

A hydrochalcone derivative represented by the formula: General formula (3)

[0014]

Embedded image (Wherein R ^{4 to} R ⁷ are each independently a hydrogen atom,
Represents up to 20 linear or branched alkyl, alkenyl, and acyl groups, and an optionally substituted benzyl group. )

Catalytic hydrogenation or catalytic hydrogenation and deprotection of a hydrochalcone derivative represented by the general formula (1)

[0016]

Embedded image (Wherein R ^{1 to} R ³ are each independently a hydrogen atom,
Represents up to 20 linear or branched alkyl, alkenyl, and acyl groups, and an optionally substituted benzyl group. )

A method for producing a flavan derivative represented by the formula: General formula (4)

[0018]

Embedded image (Wherein R ^{4 to} R ⁷ are each independently a hydrogen atom,
Represents up to 20 linear or branched alkyl, alkenyl, and acyl groups, and an optionally substituted benzyl group. )

Wherein the chalcone derivative represented by the general formula (3) is reduced:

[0020]

Embedded image (In the formula, R4 to R7 each independently represent a hydrogen atom, a linear or branched alkyl group, alkenyl group, acyl group having 1 to 20 carbon atoms, and an optionally substituted benzyl group.)

Method for producing hydrochalcone derivative represented by And a flavan derivative as described above as an active ingredient.

[0022]

Embodiments of the present invention will be described below in detail. In the general formula (1) of the present invention, R ^{1 to} R ³ each independently represent a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, an alkenyl group, an acyl group, and an optionally substituted benzyl group. Include, for example, methyl, ethyl,
Alkyl groups such as propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, octyl, nonyl, decyl, dodecyl, octadecyl, ethylhexyl, alkenyl groups such as propenyl, butenyl, pentenyl and hexenyl, and acetyl groups Acyl groups such as octanoyl group, decanoyl group and lauroyl group; and benzyl groups which may be substituted such as benzyl and p-methoxybenzyl.

Specific examples of the flavan derivative represented by the general formula (1) of the present invention include, for example, 2- (2,4-dihydroxyphenyl) -7-hydroxychroman,
(2,4-dimethoxyphenyl) -7-methoxychroman, 2- (2,4-diethoxyphenyl) -7-ethoxycycloman, 2- (2,4-dibenzyloxyphenyl) -7-benzyloxychroman, 2- (2,4-diacetoxyphenyl) -7-acetoxycycloman, 2-
(2,4-dilauroyloxyphenyl) -7-lauroyloxychroman, 2- (2,4-dihydroxyphenyl) -7-methoxychroman, 2- (2,4-dihydroxyphenyl) -7-ethoxycycloman, − (2,
4- (dihydroxyphenyl) -7-benzyloxychroman, 2- (2,4-dihydroxyphenyl) -7-acetoxycycloman, 2- (2,4-dihydroxyphenyl) -7-lauroyloxychroman, 2- (2 4-
Diethoxyphenyl) -7-methoxychroman, 2-
(2,4-diethoxyphenyl) -7-benzyloxychroman, 2- (2,4-diethoxyphenyl) -7-
Hydroxychroman, 2- (2,4-diethoxyphenyl) -7-acetoxycycloman, 2- (2,4-diethoxyphenyl) -7-lauroyloxychroman, 2-
(2,4-dimethoxyphenyl) -7-ethoxycycloman, 2- (2,4-dimethoxyphenyl) -7-benzyloxychroman, 2- (2,4-dimethoxyphenyl) -7-hydroxychroman, 2- ( 2,4-dimethoxyphenyl) -7-acetoxycycloman, 2- (2,2
4-dimethoxyphenyl) -7-lauroyloxychroman, 2- (2,4-dibenzyloxyphenyl) -7
-Ethoxycycloman, 2- (2,4-dibenzyloxyphenyl) -7-methoxychroman, 2- (2,4-dibenzyloxyphenyl) -7-hydroxychroman,
2- (2,4-dibenzyloxyphenyl) -7-acetoxycycloman, 2- (2,4-dibenzyloxyphenyl) -7-lauroyloxychroman, 2- (2,4
-Diacetoxyphenyl) -7-ethoxycycloman, 2
-(2,4-diacetoxyphenyl) -7-methoxychroman, 2- (2,4-diacetoxyphenyl) -7-
Hydroxychroman, 2- (2,4-diacetoxyphenyl) -7-benzyloxychroman, 2- (2,4-
Diacetoxyphenyl) -7-lauroyloxychroman, 2- (2,4-dilauroyloxyphenyl) -7
-Ethoxycycloman, 2- (2,4-dilauroyloxyphenyl) -7-methoxychroman, 2- (2,4-
Dilauroyloxyphenyl) -7-hydroxychroman, 2- (2,4-dilauroyloxyphenyl) -7
-Benzyloxychroman, 2- (2,4-dilauroyloxyphenyl) -7-acetoxycycloman, 2-
(2-hydroxy-4-ethoxyphenyl) -7-ethoxycycloman, 2- (2-hydroxy-4-ethoxyphenyl) -7-methoxychroman, 2- (2-hydroxy-4-ethoxyphenyl) -7-hydroxy Chroman, 2- (2-hydroxy-4-ethoxyphenyl)-
7-benzyloxychroman, 2- (2-hydroxy-
4-ethoxyphenyl) -7-acetoxycycloman, 2
-(2-hydroxy-4-ethoxyphenyl) -7-lauroyloxychroman, 2- (2-hydroxy-4-
Methoxyphenyl) -7-ethoxycycloman, 2- (2
-Hydroxy-4-methoxyphenyl) -7-methoxychroman, 2- (2-hydroxy-4-methoxyphenyl) -7-hydroxychroman, 2- (2-hydroxy-4-methoxyphenyl) -7-benzyloxychroman , 2- (2-hydroxy-4-methoxyphenyl)-
7-acetoxycycloman, 2- (2-hydroxy-4-
Methoxyphenyl) -7-lauroyloxychroman,
2- (2-hydroxy-4-benzyloxyphenyl)
-7-ethoxycycloman, 2- (2-hydroxy-4-
Benzyloxyphenyl) -7-methoxychroman, 2
-(2-hydroxy-4-benzyloxyphenyl)-
7-hydroxychroman, 2- (2-hydroxy-4-
Benzyloxyphenyl) -7-benzyloxychroman, 2- (2-hydroxy-4-benzyloxyphenyl) -7-acetoxycycloman, 2- (2-hydroxy-4-benzyloxyphenyl) -7-lauroyloxychroman, 2- (2-hydroxy-4-acetoxyphenyl) -7-ethoxycycloman, 2- (2-hydroxy-4-acetoxyphenyl) -7-methoxychroman, 2- (2-hydroxy-4-acetoxyphenyl)
-7-hydroxychroman, 2- (2-hydroxy-4
-Acetoxyphenyl) -7-benzyloxychroman, 2- (2-hydroxy-4-acetoxyphenyl)
-7-acetoxycycloman, 2- (2-hydroxy-4
-Acetoxyphenyl) -7-lauroyloxychroman, 2- (2-hydroxy-4-lauroyloxyphenyl) -7-ethoxycycloman, 2- (2-hydroxy-4-lauroyloxyphenyl) -7-methoxychroman, 2 -(2-hydroxy-4-lauroyloxyphenyl) -7-hydroxychroman, 2- (2-hydroxy-4-lauroyloxyphenyl) -7-benzyloxychroman, 2- (2-hydroxy-4-lauroyloxyphenyl) ) -7-Acetoxycycloman, 2-
(2-hydroxy-4-lauroyloxyphenyl)-
7-lauroyloxychroman, 2- (2-methoxy-
4-ethoxyphenyl) -7-ethoxycycloman, 2-
(2-methoxy-4-ethoxyphenyl) -7-methoxychroman, 2- (2-methoxy-4-ethoxyphenyl) -7-hydroxychroman, 2- (2-methoxy-
4-ethoxyphenyl) -7-benzyloxychroman, 2- (2-methoxy-4-ethoxyphenyl) -7
-Acetoxycycloman, 2- (2-methoxy-4-ethoxyphenyl) -7-lauroyloxychroman, 2-
(2-methoxy-4-benzyloxyphenyl) -7-
Ethoxycycloman, 2- (2-methoxy-4-benzyloxyphenyl) -7-methoxychroman, 2- (2-
Methoxy-4-benzyloxyphenyl) -7-hydroxychroman, 2- (2-methoxy-4-benzyloxyphenyl) -7-benzyloxychroman, 2- (2
-Methoxy-4-benzyloxyphenyl) -7-acetoxycycloman, 2- (2-methoxy-4-benzyloxyphenyl) -7-lauroyloxychroman, 2-
(2-methoxy-4-acetoxyphenyl) -7-ethoxycycloman, 2- (2-methoxy-4-acetoxyphenyl) -7-methoxychroman, 2- (2-methoxy-4-acetoxyphenyl) -7-hydroxy Chroman, 2- (2-methoxy-4-acetoxyphenyl)-
7-benzyloxychroman, 2- (2-methoxy-4
-Acetoxyphenyl) -7-acetoxycycloman, 2
-(2-methoxy-4-acetoxyphenyl) -7-lauroyloxychroman, 2- (2-methoxy-4-lauroyloxyphenyl) -7-ethoxycycloman,
-(2-methoxy-4-lauroyloxyphenyl)-
7-methoxychroman, 2- (2-methoxy-4-lauroyloxyphenyl) -7-hydroxychroman, 2
-(2-methoxy-4-lauroyloxyphenyl)-
7-benzyloxychroman, 2- (2-methoxy-4
-Lauroyloxyphenyl) -7-acetoxycycloman, 2- (2-methoxy-4-lauroyloxyphenyl) -7-lauroyloxychroman, 2- (2-methoxy-4-hydroxyphenyl) -7-ethoxycycloman, -(2-methoxy-4-hydroxyphenyl)-
7-methoxychroman, 2- (2-methoxy-4-hydroxyphenyl) -7-hydroxychroman, 2- (2
-Methoxy-4-hydroxyphenyl) -7-benzyloxychroman, 2- (2-methoxy-4-hydroxyphenyl) -7-acetoxycycloman, 2- (2-methoxy-4-hydroxyphenyl) -7-lauroyloxy Chroman, 2- (2-ethoxy-4-methoxyphenyl) -7-ethoxycycloman, 2- (2-ethoxy-4
-Methoxyphenyl) -7-methoxychroman, 2-
(2-ethoxy-4-methoxyphenyl) -7-hydroxychroman, 2- (2-ethoxy-4-methoxyphenyl) -7-benzyloxychroman, 2- (2-ethoxy-4-methoxyphenyl) -7- Acetoxycycloman, 2- (2-ethoxy-4-methoxyphenyl) -7
-Lauroyloxychroman 2- (2-ethoxy-4-
Benzyloxyphenyl) -7-ethoxycycloman, 2
-(2-ethoxy-4-benzyloxyphenyl) -7
-Methoxychroman, 2- (2-ethoxy-4-benzyloxyphenyl) -7-hydroxychroman, 2-
(2-ethoxy-4-benzyloxyphenyl) -7-
Benzyloxychroman, 2- (2-ethoxy-4-benzyloxyphenyl) -7-acetoxycycloman,
-(2-ethoxy-4-benzyloxyphenyl) -7
-Lauroyloxychroman, 2- (2-ethoxy-4)
-Acetoxyphenyl) -7-ethoxycycloman, 2-
(2-ethoxy-4-acetoxyphenyl) -7-methoxychroman, 2- (2-ethoxy-4-acetoxyphenyl) -7-hydroxychroman, 2- (2-ethoxy-4-acetoxyphenyl) -7-benzyl Oxychroman, 2- (2-ethoxy-4-acetoxyphenyl) -7-acetoxycycloman, 2- (2-ethoxy-
4-acetoxyphenyl) -7-lauroyloxychroman, 2- (2-ethoxy-4-lauroyloxyphenyl) -7-ethoxycycloman, 2- (2-ethoxy-
4-lauroyloxyphenyl) -7-methoxychroman, 2- (2-ethoxy-4-lauroyloxyphenyl) -7-hydroxychroman, 2- (2-ethoxy-
4-lauroyloxyphenyl) -7-benzyloxychroman, 2- (2-ethoxy-4-lauroyloxyphenyl) -7-acetoxycycloman, 2- (2-ethoxy-4-lauroyloxyphenyl) -7-lauroyloxy Chroman, 2- (2-ethoxy-4-hydroxyphenyl) -7-ethoxycycloman, 2- (2-ethoxy-4-hydroxyphenyl) -7-methoxychroman, 2- (2-ethoxy-4-hydroxyphenyl) −
7-hydroxychroman, 2- (2-ethoxy-4-hydroxyphenyl) -7-benzyloxychroman, 2
-(2-ethoxy-4-hydroxyphenyl) -7-acetoxycycloman, 2- (2-ethoxy-4-hydroxyphenyl) -7-lauroyloxychroman, 2-
(2-benzyloxy-4-methoxyphenyl) -7-
Ethoxycycloman, 2- (2-benzyloxy-4-methoxyphenyl) -7-methoxychroman, 2- (2-
Benzyloxy-4-methoxyphenyl) -7-hydroxychroman, 2- (2-benzyloxy-4-methoxyphenyl) -7-benzyloxychroman, 2- (2
-Benzyloxy-4-methoxyphenyl) -7-acetoxycycloman, 2- (2-benzyloxy-4-methoxyphenyl) -7-lauroyloxychroman, 2-
(2-benzyloxy-4-ethoxyphenyl) -7-
Ethoxycycloman, 2- (2-benzyloxy-4-ethoxyphenyl) -7-methoxychroman, 2- (2-
Benzyloxy-4-ethoxyphenyl) -7-hydroxychroman, 2- (2-benzyloxy-4-ethoxyphenyl) -7-benzyloxychroman, 2- (2
-Benzyloxy-4-ethoxyphenyl) -7-acetoxycycloman, 2- (2-benzyloxy-4-ethoxyphenyl) -7-lauroyloxychroman, 2-
(2-benzyloxy-4-acetoxyphenyl) -7
-Ethoxycycloman, 2- (2-benzyloxy-4-
(Acetoxyphenyl) -7-methoxychroman, 2-
(2-benzyloxy-4-acetoxyphenyl) -7
-Hydroxychroman, 2- (2-benzyloxy-4)
-Acetoxyphenyl) -7-benzyloxychroman, 2- (2-benzyloxy-4-acetoxyphenyl) -7-acetoxycycloman, 2- (2-benzyloxy-4-acetoxyphenyl) -7-lauroyloxychroman, 2- (2-benzyloxy-4-lauroyloxyphenyl) -7-ethoxycycloman, 2- (2
-Benzyloxy-4-lauroyloxyphenyl)-
7-methoxychroman, 2- (2-benzyloxy-4)
-Lauroyloxyphenyl) -7-hydroxychroman, 2- (2-benzyloxy-4-lauroyloxyphenyl) -7-benzyloxychroman, 2- (2-
Benzyloxy-4-lauroyloxyphenyl) -7
-Acetoxycycloman, 2- (2-benzyloxy-4)
-Lauroyloxyphenyl) -7-lauroyloxychroman, 2- (2-benzyloxy-4-hydroxyphenyl) -7-ethoxycycloman, 2- (2-benzyloxy-4-hydroxyphenyl) -7-methoxychroman, 2- (2-benzyloxy-4-hydroxyphenyl) -7-hydroxychroman, 2- (2-benzyloxy-4-hydroxyphenyl) -7-benzyloxychroman, 2- (2-benzyloxy-4-hydroxy Phenyl) -7-acetoxycycloman, 2- (2-
Benzyloxy-4-hydroxyphenyl) -7-lauroyloxychroman, 2- (2-acetoxy-4-methoxyphenyl) -7-ethoxycycloman, 2- (2-
Acetoxy-4-methoxyphenyl) -7-methoxychroman, 2- (2-acetoxy-4-methoxyphenyl) -7-hydroxychroman, 2- (2-acetoxy-4-methoxyphenyl) -7-benzyloxychroman, 2- (2-acetoxy-4-methoxyphenyl)-
7-acetoxycycloman, 2- (2-acetoxy-4-
Methoxyphenyl) -7-lauroyloxychroman,
2- (2-acetoxy-4-benzyloxyphenyl)
-7-ethoxycycloman, 2- (2-acetoxy-4-
Benzyloxyphenyl) -7-methoxychroman, 2
-(2-acetoxy-4-benzyloxyphenyl)-
7-hydroxychroman, 2- (2-acetoxy-4-
Benzyloxyphenyl) -7-benzyloxychroman, 2- (2-acetoxy-4-benzyloxyphenyl) -7-acetoxycycloman, 2- (2-acetoxy-4-benzyloxyphenyl) -7-lauroyloxychroman, 2- (2-acetoxyphenyl-4-ethoxy) -7-ethoxycycloman, 2- (2-acetoxy-4-ethoxyphenyl) -7-methoxychroman, 2
-(2-acetoxy-4-ethoxyphenyl) -7-hydroxychroman, 2- (2-acetoxy-4-ethoxyphenyl) -7-benzyloxychroman, 2- (2
-Acetoxy-4-ethoxyphenyl) -7-acetoxycycloman, 2- (2-acetoxy-4-ethoxyphenyl) -7-lauroyloxychroman, 2- (2-acetoxy-4-lauroyloxyphenyl) -7-ethoxy Chroman, 2- (2-acetoxy-4-lauroyloxyphenyl) -7-methoxychroman, 2- (2-
Acetoxy-4-lauroyloxyphenyl) -7-hydroxychroman, 2- (2-acetoxy-4-lauroyloxyphenyl) -7-benzyloxychroman,
2- (2-acetoxy-4-lauroyloxyphenyl) -7-acetoxycycloman, 2- (2-acetoxy-4-lauroyloxyphenyl) -7-lauroyloxychroman, 2- (2-acetoxy-4-hydroxyphenyl) ) -7-Ethoxycycloman, 2- (2-acetoxy-4-hydroxyphenyl) -7-methoxychroman, 2- (2-acetoxy-4-hydroxyphenyl)
-7-hydroxychroman, 2- (2-acetoxy-4)
-Hydroxyphenyl) -7-benzyloxychroman, 2- (2-acetoxy-4-hydroxyphenyl)
-7-acetoxycycloman, 2- (2-acetoxy-4
-Hydroxyphenyl) -7-lauroyloxychroman, 2- (2-lauroyloxy-4-methoxyphenyl) -7-ethoxycycloman, 2- (2-lauroyloxy-4-methoxyphenyl) -7-methoxychroman, 2 -(2-lauroyloxy-4-methoxyphenyl) -7-hydroxychroman, 2- (2-lauroyloxy-4-methoxyphenyl) -7-benzyloxychroman, 2- (2-lauroyloxy-4-methoxyphenyl) ) -7-Acetoxycycloman, 2- (2-lauroyloxy-4-methoxyphenyl) -7-lauroyloxychroman, 2- (2-lauroyloxy-4-
Benzyloxyphenyl) -7-ethoxycycloman, 2
-(2-lauroyloxy-4-benzyloxyphenyl) -7-methoxychroman, 2- (2-lauroyloxy-4-benzyloxyphenyl) -7-hydroxychroman, 2- (2-lauroyloxy-4-benzyl Oxyphenyl) -7-benzyloxychroman, 2-
(2-Lauroyloxy-4-benzyloxyphenyl) -7-acetoxycycloman, 2- (2-lauroyloxy-4-benzyloxyphenyl) -7-lauroyloxychroman, 2- (2-lauroyloxy-4-
(Acetoxyphenyl) -7-ethoxycycloman, 2-
(2-lauroyloxy-4-acetoxyphenyl)-
7-methoxychroman, 2- (2-lauroyloxy-
4-acetoxyphenyl) -7-hydroxychroman,
2- (2-lauroyloxy-4-acetoxyphenyl) -7-benzyloxychroman, 2- (2-lauroyloxy-4-acetoxyphenyl) -7-acetoxycycloman, 2- (2-lauroyloxy-4-acetoxy) Phenyl) -7-lauroyloxychroman, 2-
(2-lauroyloxy-4-ethoxyphenyl) -7
-Ethoxycycloman, 2- (2-lauroyloxy-4)
-Ethoxyphenyl) -7-methoxychroman, 2-
(2-lauroyloxy-4-ethoxyphenyl) -7
-Hydroxychroman, 2- (2-lauroyloxy-
4-ethoxyphenyl) -7-benzyloxychroman, 2- (2-lauroyloxy-4-ethoxyphenyl) -7-acetoxycycloman, 2- (2-lauroyloxy-4-ethoxyphenyl) -7-lauroyloxychroman 2- (2-lauroyloxy-4-hydroxyphenyl) -7-ethoxycycloman, 2- (2-lauroyloxy-4-hydroxyphenyl) -7-methoxychroman, 2- (2-lauroyloxy-4-hydroxy) Phenyl) -7-hydroxychroman, 2- (2
-Lauroyloxy-4-hydroxyphenyl) -7-
Benzyloxychroman, 2- (2-lauroyloxy-4-hydroxyphenyl) -7-acetoxycycloman, 2- (2-lauroyloxy-4-hydroxyphenyl) -7-lauroyloxychroman, 2- (2,4
-Dipropenyloxyphenyl) -7-propenyloxychroman, 2- (2,4-dipropenyloxyphenyl) -7-hydroxychroman, 2- (2,4-dipropenyloxyphenyl) -7-methoxychroman, −
(2-hydroxy-4-propenyloxyphenyl)-
7-hydroxychroman, 2- (2-propenyloxy-4-hydroxyphenyl) -7-hydroxychroman, 2- (2-propenyloxy-4-hydroxyphenyl) -7-propenyloxychroman, 2- (2,4
-Dihydroxyphenyl) -7-propenyloxychroman, 2- (2,4-dimethoxyphenyl) -7-propenyloxychroman, and the like, but are not limited thereto. These may be used alone or in combination of two or more.

In the general formula (3) of the present invention, R ^{4 to} R ⁷ each independently represent a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, an alkenyl group, an acyl group, and an optionally substituted benzyl group. For example, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, t
alkyl groups such as tert-butyl, pentyl, hexyl, octyl, nonyl, decyl, dodecyl, octadecyl, ethylhexyl, propenyl, butenyl, pentenyl,
An alkenyl group such as hexenyl, an acetyl group, an octanoyl group, a decanoyl group, an acyl group such as a lauroyl group, and an optionally substituted benzyl group such as benzyl and p-methoxybenzyl are exemplified.

In the present invention, the hydroform represented by the general formula (3)
Specific examples of chalcone derivatives include, for example, 1,3-
(2,4-dibenzyloxyphenyl) -3-hydroxy
C-1-propene, 1,3- (2,4-diethoxyfe
Nyl) -3-hydroxy-1-propene, 1,3-
(2,4-dimethoxyphenyl) -3-hydroxy-1
-Propene, 1,3- (2,4-dihydroxyphenyl)
L) -3-hydroxy-1-propene, 1,3- (2,
4-diacetoxyphenyl) -3-hydroxy-1-prop
Lopen, 1,3- (2,4-dilauroyloxyphenyl)
1) -3-hydroxy-1-propene, 1- (2,4-
Dibenzyloxyphenyl) -3- (2,4-diethoxy
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dibenzyloxyphenyl) -3- (2,4
-Dimethoxyphenyl) -3-hydroxy-1-prope
, 1- (2,4-dibenzyloxyphenyl) -3-
(2,4-dihydroxyphenyl) -3-hydroxy-
1-propene, 1- (2,4-dibenzyloxyphenyl)
) -3- (2,4-diacetoxyphenyl) -3-h
Droxy-1-propene, 1- (2,4-dibenzylo)
(Xyphenyl) -3- (2,4-dilauroyloxyf)
Enyl) -3-hydroxy-1-propene, 1- (2,
4-diethoxyphenyl) -3- (2,4-dimethoxy
Phenyl) -3-hydroxy-1-propene, 1-
(2,4-diethoxyphenyl) -3- (2,4-dibe
Ndyloxyphenyl) -3-hydroxy-1-prope
1- (2,4-diethoxyphenyl) -3- (2,
4-dihydroxyphenyl) -3-hydroxy-1-prop
Lopen, 1- (2,4-diethoxyphenyl) -3-
(2,4-diacetoxyphenyl) -3-hydroxy-
1-propene, 1- (2,4-diethoxyphenyl)-
3- (2,4-dilauroyloxyphenyl) -3-h
Droxy-1-propene, 1- (2,4-dimethoxyp
Enyl) -3- (2,4-diethoxyphenyl) -3-
Hydroxy-1-propene, 1- (2,4-dimethoxy
Phenyl) -3- (2,4-dihydroxyphenyl)-
3-hydroxy-1-propene, 1- (2,4-dimethoate)
(Xyphenyl) -3- (2,4-dibenzyloxyphene)
Nyl) -3-hydroxy-1-propene, 1- (2,4
-Dimethoxyphenyl) -3- (2,4-diacetoxy
Phenyl) -3-hydroxy-1-propene, 1-
(2,4-dimethoxyphenyl) -3- (2,4-dila
(Uroyloxyphenyl) -3-hydroxy-1-pro
Pen, 1- (2,4-dihydroxyphenyl) -3-
(2,4-diethoxyphenyl) -3-hydroxy-1
-Propene, 1- (2,4-dihydroxyphenyl)-
3- (2,4-dimethoxyphenyl) -3-hydroxy
-1-propene, 1- (2,4-dihydroxyphenyl)
) -3- (2,4-dibenzyloxyphenyl) -3
-Hydroxy-1-propene, 1- (2,4-dihydro
(Xyphenyl) -3- (2,4-diacetoxyphenyl)
1) -3-hydroxy-1-propene, 1- (2,4-
Dihydroxyphenyl) -3- (2,4-dilauroyl
Oxyphenyl) -3-hydroxy-1-propene, 1
-(2,4-diacetoxyphenyl) -3- (2,4-
Dimethoxyphenyl) -3-hydroxy-1-prope
1- (2,4-diacetoxyphenyl) -3-
(2,4-diethoxyphenyl) -3-hydroxy-1
-Propene, 1- (2,4-diacetoxyphenyl)-
3- (2,4-dibenzyloxyphenyl) -3-hydride
Roxy-1-propene, 1- (2,4-diacetoxyf
Enyl) -3- (2,4-dihydroxyphenyl) -3
-Hydroxy-1-propene, 1- (2,4-diacetate)
(Xyphenyl) -3- (2,4-dilauroyloxyf)
Enyl) -3-hydroxy-1-propene, 1- (2,
4-dilauroyloxyphenyl) -3- (2,4-di
Methoxyphenyl) -3-hydroxy-1-propene,
1- (2,4-dilauroyloxyphenyl) -3-
(2,4-diethoxyphenyl) -3-hydroxy-1
-Propene, 1- (2,4-dilauroyloxyphenyl)
) -3- (2,4-dibenzyloxyphenyl) -3
-Hydroxy-1-propene, 1- (2,4-dilauro
Yloxyphenyl) -3- (2,4-dihydroxyf
Enyl) -3-hydroxy-1-propene, 1- (2,
4-dilauroyloxyphenyl) -3- (2,4-di
(Acetoxyphenyl) -3-hydroxy-1-prope
, 1- (2,4-dibenzyloxyphenyl) -3-
(2-benzyloxy-4-ethoxyphenyl) -3-
Hydroxy-1-propene, 1- (2,4-dibenzyl)
Oxyphenyl) -3- (2-benzyloxy-4-me
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2,4-dibenzyloxyphenyl) -3- (2-
Benzyloxy-4-hydroxyphenyl) -3-hydrido
Roxy-1-propene, 1- (2,4-dibenzyloxy)
(Ciphenyl) -3- (2-benzyloxy-4-aceto)
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dibenzyloxyphenyl) -3- (2-b
Benzyloxy-4-lauroyloxyphenyl) -3-
Hydroxy-1-propene, 1- (2,4-dibenzyl)
Oxyphenyl) -3- (2-ethoxy-4-methoxy
Phenyl) -3-hydroxy-1-propene, 1-
(2,4-dibenzyloxyphenyl) -3- (2-e
Toxi-4-hydroxyphenyl) -3-hydroxy-
1-propene, 1- (2,4-dibenzyloxyphenyl)
) -3- (2-ethoxy-4-benzyloxyphenyl)
1) -3-hydroxy-1-propene, 1- (2,4-
Dibenzyloxyphenyl) -3- (2-ethoxy-4
-Acetoxyphenyl) -3-hydroxy-1-prope
, 1- (2,4-dibenzyloxyphenyl) -3-
(2-ethoxy-4-lauroyloxyphenyl) -3
-Hydroxy-1-propene, 1- (2,4-dibenzyl)
Roxyphenyl) -3- (2-methoxy-4-ethoxy)
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dibenzyloxyphenyl) -3- (2-me
Toxi-4-hydroxyphenyl) -3-hydroxy-
1-propene, 1- (2,4-dibenzyloxyphenyl)
) -3- (2-methoxy-4-benzyloxyphenyl)
1) -3-hydroxy-1-propene, 1- (2,4-
Dibenzyloxyphenyl) -3- (2-methoxy-4
-Acetoxyphenyl) -3-hydroxy-1-prope
, 1- (2,4-dibenzyloxyphenyl) -3-
(2-methoxy-4-lauroyloxyphenyl) -3
-Hydroxy-1-propene, 1- (2,4-dibenzyl)
Ruoxyphenyl) -3- (2-hydroxy-4-etho
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dibenzyloxyphenyl) -3- (2-h
(Droxy-4-methoxyphenyl) -3-hydroxy-
1-propene, 1- (2,4-dibenzyloxyphenyl)
) -3- (2-hydroxy-4-benzyloxyphene)
Nyl) -3-hydroxy-1-propene, 1- (2,4
-Dibenzyloxyphenyl) -3- (2-hydroxy
-4-acetoxyphenyl) -3-hydroxy-1-prop
Lopen, 1- (2,4-dibenzyloxyphenyl)-
3- (2-hydroxy-4-lauroyloxyphenyl)
1) -3-hydroxy-1-propene, 1- (2,4-
Dibenzyloxyphenyl) -3- (2-acetoxy-
4-ethoxyphenyl) -3-hydroxy-1-prope
, 1- (2,4-dibenzyloxyphenyl) -3-
(2-acetoxy-4-methoxyphenyl) -3-hydride
Roxy-1-propene, 1- (2,4-dibenzyloxy)
(Ciphenyl) -3- (2-acetoxy-4-benzylo)
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dibenzyloxyphenyl) -3- (2-a
Cetoxy-4-hydroxyphenyl) -3-hydroxy
-1-propene, 1- (2,4-dibenzyloxyphene)
Nil) -3- (2-acetoxy-4-lauroyloxy
Phenyl) -3-hydroxy-1-propene, 1-
(2,4-dibenzyloxyphenyl) -3- (2-la
Uroyloxy-4-ethoxyphenyl) -3-hydro
Xy-1-propene, 1- (2,4-dibenzyloxy)
Phenyl) -3- (2-lauroyloxy-4-methoxy)
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dibenzyloxyphenyl) -3- (2-la
Uroyloxy-4-benzyloxyphenyl) -3-
Hydroxy-1-propene, 1- (2,4-dibenzyl)
Oxyphenyl) -3- (2-lauroyloxy-4-
(Hydroxyphenyl) -3-hydroxy-1-prope
, 1- (2,4-dibenzyloxyphenyl) -3-
(2-lauroyloxy-4-acetoxyphenyl)-
3-hydroxy-1-propene, 1- (2,4-diet
(Xyphenyl) -3- (2-benzyloxy-4-ethoxy)
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2,4-diethoxyphenyl) -3- (2-benzyl
Oxy-4-methoxyphenyl) -3-hydroxy-1
-Propene, 1- (2,4-diethoxyphenyl) -3
-(2-benzyloxy-4-hydroxyphenyl)-
3-hydroxy-1-propene, 1- (2,4-diet
(Xyphenyl) -3- (2-benzyloxy-4-ace
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2,4-diethoxyphenyl) -3- (2-benzyl)
Ruoxy-4-lauroyloxyphenyl) -3-hydrido
Roxy-1-propene, 1- (2,4-diethoxyfe)
Nyl) -3- (2-ethoxy-4-methoxyphenyl)
-3-hydroxy-1-propene, 1- (2,4-die
Toxyphenyl) -3- (2-ethoxy-4-hydroxy
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2,4-diethoxyphenyl) -3- (2-ethoxy)
-4-benzyloxyphenyl) -3-hydroxy-1
-Propene, 1- (2,4-diethoxyphenyl) -3
-(2-ethoxy-4-acetoxyphenyl) -3-h
Droxy-1-propene, 1- (2,4-diethoxyf)
Enyl) -3- (2-ethoxy-4-lauroyloxy
Phenyl) -3-hydroxy-1-propene, 1-
(2,4-diethoxyphenyl) -3- (2-methoxy
-4-ethoxyphenyl) -3-hydroxy-1-pro
Pen, 1- (2,4-diethoxyphenyl) -3- (2
-Methoxy-4-hydroxyphenyl) -3-hydroxy
C-1-propene, 1- (2,4-diethoxyphenyl)
) -3- (2-methoxy-4-benzyloxyphenyl)
1) -3-hydroxy-1-propene, 1- (2,4-
Diethoxyphenyl) -3- (2-methoxy-4-ace
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2,4-diethoxyphenyl) -3- (2-methoxy
Ci-4-lauroyloxyphenyl) -3-hydroxy
-1-propene, 1- (2,4-diethoxyphenyl)
-3- (2-Hydroxy-4-ethoxyphenyl) -3
-Hydroxy-1-propene, 1- (2,4-diethoxy)
(Ciphenyl) -3- (2-hydroxy-4-methoxyphenyl)
Enyl) -3-hydroxy-1-propene, 1- (2,
4-diethoxyphenyl) -3- (2-hydroxy-4
-Benzyloxyphenyl) -3-hydroxy-1-prop
Lopen, 1- (2,4-diethoxyphenyl) -3-
(2-hydroxy-4-acetoxyphenyl) -3-h
Droxy-1-propene, 1- (2,4-diethoxyf)
Enyl) -3- (2-hydroxy-4-lauroyloxy
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2,4-diethoxyphenyl) -3- (2-acetoxy
C-4-ethoxyphenyl) -3-hydroxy-1-prop
Lopen, 1- (2,4-diethoxyphenyl) -3-
(2-acetoxy-4-methoxyphenyl) -3-hydride
Roxy-1-propene, 1- (2,4-diethoxyfe)
Nil) -3- (2-acetoxy-4-benzyloxyf
Enyl) -3-hydroxy-1-propene, 1- (2,
4-diethoxyphenyl) -3- (2-acetoxy-4
-Hydroxyphenyl) -3-hydroxy-1-prope
1- (2,4-diethoxyphenyl) -3- (2-
Acetoxy-4-lauroyloxyphenyl) -3-h
Droxy-1-propene, 1- (2,4-diethoxyf)
Enyl) -3- (2-lauroyloxy-4-ethoxy)
Phenyl) -3-hydroxy-1-propene, 1-
(2,4-diethoxyphenyl) -3- (2-lauroy
Ruoxy-4-methoxyphenyl) -3-hydroxy-
1-propene, 1- (2,4-diethoxyphenyl)-
3- (2-lauroyloxy-4-benzyloxyfe
Nyl) -3-hydroxy-1-propene, 1- (2,4
-Diethoxyphenyl) -3- (2-lauroyloxy
-4-Hydroxyphenyl) -3-hydroxy-1-p
Lopen, 1- (2,4-diethoxyphenyl) -3-
(2-lauroyloxy-4-acetoxyphenyl)-
3-hydroxy-1-propene, 1- (2,4-dimethoate)
(Xyphenyl) -3- (2-benzyloxy-4-ethoxy)
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dimethoxyphenyl) -3- (2-benzyl
Oxy-4-methoxyphenyl) -3-hydroxy-1
-Propene, 1- (2,4-dimethoxyphenyl) -3
-(2-benzyloxy-4-hydroxyphenyl)-
3-hydroxy-1-propene, 1- (2,4-dimethoate)
(Xyphenyl) -3- (2-benzyloxy-4-ace
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2,4-dimethoxyphenyl) -3- (2-benzyl)
Ruoxy-4-lauroyloxyphenyl) -3-hydrido
Roxy-1-propene, 1- (2,4-dimethoxyfe
Nyl) -3- (2-ethoxy-4-methoxyphenyl)
-3-Hydroxy-1-propene, 1- (2,4-dim
Toxyphenyl) -3- (2-ethoxy-4-hydroxy
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dimethoxyphenyl) -3- (2-ethoxy
-4-benzyloxyphenyl) -3-hydroxy-1
-Propene, 1- (2,4-dimethoxyphenyl) -3
-(2-ethoxy-4-acetoxyphenyl) -3-h
Droxy-1-propene, 1- (2,4-dimethoxyp
Enyl) -3- (2-ethoxy-4-lauroyloxy
Phenyl) -3-hydroxy-1-propene, 1-
(2,4-dimethoxyphenyl) -3- (2-methoxy
-4-ethoxyphenyl) -3-hydroxy-1-pro
Pen, 1- (2,4-dimethoxyphenyl) -3- (2
-Methoxy-4-hydroxyphenyl) -3-hydroxy
C-1-propene, 1- (2,4-dimethoxyphenyl)
) -3- (2-methoxy-4-benzyloxyphenyl)
1) -3-hydroxy-1-propene, 1- (2,4-
Dimethoxyphenyl) -3- (2-methoxy-4-ace
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2,4-dimethoxyphenyl) -3- (2-methoxy
Ci-4-lauroyloxyphenyl) -3-hydroxy
-1-propene, 1- (2,4-dimethoxyphenyl)
-3- (2-Hydroxy-4-ethoxyphenyl) -3
-Hydroxy-1-propene, 1- (2,4-dimethoxy)
(Ciphenyl) -3- (2-hydroxy-4-methoxyphenyl)
Enyl) -3-hydroxy-1-propene, 1- (2,
4-dimethoxyphenyl) -3- (2-hydroxy-4
-Benzyloxyphenyl) -3-hydroxy-1-prop
Lopen, 1- (2,4-dimethoxyphenyl) -3-
(2-hydroxy-4-acetoxyphenyl) -3-h
Droxy-1-propene, 1- (2,4-dimethoxyp
Enyl) -3- (2-hydroxy-4-lauroyloxy
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dimethoxyphenyl) -3- (2-acetoxy
C-4-ethoxyphenyl) -3-hydroxy-1-prop
Lopen, 1- (2,4-dimethoxyphenyl) -3-
(2-acetoxy-4-methoxyphenyl) -3-hydride
Roxy-1-propene, 1- (2,4-dimethoxyfe
Nil) -3- (2-acetoxy-4-benzyloxyf
Enyl) -3-hydroxy-1-propene, 1- (2,
4-dimethoxyphenyl) -3- (2-acetoxy-4
-Hydroxyphenyl) -3-hydroxy-1-prope
1- (2,4-dimethoxyphenyl) -3- (2-
Acetoxy-4-lauroyloxyphenyl) -3-h
Droxy-1-propene, 1- (2,4-dimethoxyp
Enyl) -3- (2-lauroyloxy-4-ethoxy)
Phenyl) -3-hydroxy-1-propene, 1-
(2,4-dimethoxyphenyl) -3- (2-lauroy
Ruoxy-4-methoxyphenyl) -3-hydroxy-
1-propene, 1- (2,4-dimethoxyphenyl)-
3- (2-lauroyloxy-4-benzyloxyfe
Nyl) -3-hydroxy-1-propene, 1- (2,4
-Dimethoxyphenyl) -3- (2-lauroyloxy
-4-Hydroxyphenyl) -3-hydroxy-1-p
Lopen, 1- (2,4-dimethoxyphenyl) -3-
(2-lauroyloxy-4-acetoxyphenyl)-
3-hydroxy-1-propene, 1- (2,4-dihydride
Roxyphenyl) -3- (2-benzyloxy-4-e
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2,4-dihydroxyphenyl) -3- (2-ben
(Diloxy-4-methoxyphenyl) -3-hydroxy
-1-propene, 1- (2,4-dihydroxyphenyl)
) -3- (2-benzyloxy-4-hydroxyphene)
Nyl) -3-hydroxy-1-propene, 1- (2,4
-Dihydroxyphenyl) -3- (2-benzyloxy)
-4-acetoxyphenyl) -3-hydroxy-1-prop
Lopen, 1- (2,4-dihydroxyphenyl) -3-
(2-benzyloxy-4-lauroyloxyphenyl
1) -3-hydroxy-1-propene, 1- (2,4-
Dihydroxyphenyl) -3- (2-ethoxy-4-me
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2,4-dihydroxyphenyl) -3- (2-ethoxy
(Xy-4-hydroxyphenyl) -3-hydroxy-1
-Propene, 1- (2,4-dihydroxyphenyl)-
3- (2-ethoxy-4-benzyloxyphenyl)-
3-hydroxy-1-propene, 1- (2,4-dihydride
Roxyphenyl) -3- (2-ethoxy-4-acetoxy
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dihydroxyphenyl) -3- (2-ethoxy
Ci-4-lauroyloxyphenyl) -3-hydroxy
-1-propene, 1- (2,4-dihydroxyphenyl)
) -3- (2-methoxy-4-ethoxyphenyl)-
3-hydroxy-1-propene, 1- (2,4-dihydride
Roxyphenyl) -3- (2-methoxy-4-hydroxy
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dihydroxyphenyl) -3- (2-methoxy)
(S-4-benzyloxyphenyl) -3-hydroxy-
1-propene, 1- (2,4-dihydroxyphenyl)
-3- (2-Methoxy-4-acetoxyphenyl) -3
-Hydroxy-1-propene, 1- (2,4-dihydro
(Xyphenyl) -3- (2-methoxy-4-lauroyl)
Oxyphenyl) -3-hydroxy-1-propene, 1
-(2,4-dihydroxyphenyl) -3- (2-hydrido
Roxy-4-ethoxyphenyl) -3-hydroxy-1
-Propene, 1- (2,4-dihydroxyphenyl)-
3- (2-hydroxy-4-methoxyphenyl) -3-
Hydroxy-1-propene, 1- (2,4-dihydroxy
(Ciphenyl) -3- (2-hydroxy-4-benzylo)
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dihydroxyphenyl) -3- (2-hydro
(Xy-4-acetoxyphenyl) -3-hydroxy-1
-Propene, 1- (2,4-dihydroxyphenyl)-
3- (2-hydroxy-4-lauroyloxyphenyl)
1) -3-hydroxy-1-propene, 1- (2,4-
Dihydroxyphenyl) -3- (2-acetoxy-4-
Ethoxyphenyl) -3-hydroxy-1-propene,
1- (2,4-dihydroxyphenyl) -3- (2-a
Cetoxy-4-methoxyphenyl) -3-hydroxy-
1-propene, 1- (2,4-dihydroxyphenyl)
-3- (2-acetoxy-4-benzyloxyphenyl)
1) -3-hydroxy-1-propene, 1- (2,4-
Dihydroxyphenyl) -3- (2-acetoxy-4-
(Hydroxyphenyl) -3-hydroxy-1-prope
1- (2,4-dihydroxyphenyl) -3- (2
-Acetoxy-4-lauroyloxyphenyl) -3-
Hydroxy-1-propene, 1- (2,4-dihydroxy
(Ciphenyl) -3- (2-lauroyloxy-4-ethoxy
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dihydroxyphenyl) -3- (2-lauro
Yloxy-4-methoxyphenyl) -3-hydroxy
-1-propene, 1- (2,4-dihydroxyphenyl)
) -3- (2-Lauroyloxy-4-benzyloxy)
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dihydroxyphenyl) -3- (2-lauro
Yloxy-4-hydroxyphenyl) -3-hydroxy
C-1-propene, 1- (2,4-dihydroxyphenyl)
) -3- (2-Lauroyloxy-4-acetoxyf)
Enyl) -3-hydroxy-1-propene, 1- (2,
4-diacetoxyphenyl) -3- (2-benzyloxy
C-4-ethoxyphenyl) -3-hydroxy-1-prop
Lopen, 1- (2,4-diacetoxyphenyl) -3-
(2-benzyloxy-4-methoxyphenyl) -3-
Hydroxy-1-propene, 1- (2,4-diacetoxy)
(Ciphenyl) -3- (2-benzyloxy-4-hydro
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2,4-diacetoxyphenyl) -3- (2-benzyl)
Ruoxy-4-acetoxyphenyl) -3-hydroxy
-1-propene, 1- (2,4-diacetoxyphenyl)
) -3- (2-benzyloxy-4-lauroyloxy)
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2,4-diacetoxyphenyl) -3- (2-ethoxy
C-4-methoxyphenyl) -3-hydroxy-1-prop
Lopen, 1- (2,4-diacetoxyphenyl) -3-
(2-ethoxy-4-hydroxyphenyl) -3-hydride
Roxy-1-propene, 1- (2,4-diacetoxyf
Enyl) -3- (2-ethoxy-4-benzyloxyf
Enyl) -3-hydroxy-1-propene, 1- (2,
4-diacetoxyphenyl) -3- (2-ethoxy-4
-Acetoxyphenyl) -3-hydroxy-1-prope
1- (2,4-diacetoxyphenyl) -3- (2
-Ethoxy-4-lauroyloxyphenyl) -3-h
Droxy-1-propene, 1- (2,4-diacetoxy
Phenyl) -3- (2-methoxy-4-ethoxyphenyl)
1) -3-hydroxy-1-propene, 1- (2,4-
Diacetoxyphenyl) -3- (2-methoxy-4-h
Droxyphenyl) -3-hydroxy-1-propene,
1- (2,4-diacetoxyphenyl) -3- (2-meth
Toxy-4-benzyloxyphenyl) -3-hydroxy
C-1-propene, 1- (2,4-diacetoxyphenyi)
) -3- (2-methoxy-4-acetoxyphenyl)
-3-Hydroxy-1-propene, 1- (2,4-dia
Cetoxyphenyl) -3- (2-methoxy-4-lauro
Yloxyphenyl) -3-hydroxy-1-prope
1- (2,4-diacetoxyphenyl) -3- (2
-Hydroxy-4-ethoxyphenyl) -3-hydroxy
C-1-propene, 1- (2,4-diacetoxyphenyi)
) -3- (2-hydroxy-4-methoxyphenyl)
-3-Hydroxy-1-propene, 1- (2,4-dia
Sethoxyphenyl) -3- (2-hydroxy-4-ben
(Diloxyphenyl) -3-hydroxy-1-prope
1- (2,4-diacetoxyphenyl) -3- (2
-Hydroxy-4-acetoxyphenyl) -3-hydro
Xy-1-propene, 1- (2,4-diacetoxyfe)
Nyl) -3- (2-hydroxy-4-lauroyloxy
Phenyl) -3-hydroxy-1-propene, 1-
(2,4-diacetoxyphenyl) -3- (2-aceto
(Xy-4-ethoxyphenyl) -3-hydroxy-1-
Propene, 1- (2,4-diacetoxyphenyl) -3
-(2-acetoxy-4-methoxyphenyl) -3-h
Droxy-1-propene, 1- (2,4-diacetoxy
Phenyl) -3- (2-acetoxy-4-benzyloxy)
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2,4-diacetoxyphenyl) -3- (2-aceto
(Xy-4-hydroxyphenyl) -3-hydroxy-1
-Propene, 1- (2,4-diacetoxyphenyl)-
3- (2-acetoxy-4-lauroyloxyphenyl)
1) -3-hydroxy-1-propene, 1- (2,4-
Diacetoxyphenyl) -3- (2-lauroyloxy
-4-ethoxyphenyl) -3-hydroxy-1-pro
Pen, 1- (2,4-diacetoxyphenyl) -3-
(2-Lauroyloxy-4-methoxyphenyl) -3
-Hydroxy-1-propene, 1- (2,4-diacetate)
(Xyphenyl) -3- (2-lauroyloxy-4-be)
Ndyloxyphenyl) -3-hydroxy-1-prope
1- (2,4-diacetoxyphenyl) -3- (2
-Lauroyloxy-4-hydroxyphenyl) -3-
Hydroxy-1-propene, 1- (2,4-diacetoxy)
(Ciphenyl) -3- (2-lauroyloxy-4-ace
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2,4-Dilauroyloxyphenyl) -3- (2
-Benzyloxy-4-ethoxyphenyl) -3-hydrido
Roxy-1-propene, 1- (2,4-dilauroylo
(Xyphenyl) -3- (2-benzyloxy-4-methoate)
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dilauroyloxyphenyl) -3- (2-
Benzyloxy-4-hydroxyphenyl) -3-hydrido
Roxy-1-propene, 1- (2,4-dilauroylo
(Xyphenyl) -3- (2-benzyloxy-4-ace
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2,4-Dilauroyloxyphenyl) -3- (2
-Benzyloxy-4-lauroyloxyphenyl)-
3-hydroxy-1-propene, 1- (2,4-dilau)
Royloxyphenyl) -3- (2-ethoxy-4-me
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2,4-Dilauroyloxyphenyl) -3- (2
-Ethoxy-4-hydroxyphenyl) -3-hydroxy
C-1-propene, 1- (2,4-dilauroyloxy)
Phenyl) -3- (2-ethoxy-4-benzyloxy
Phenyl) -3-hydroxy-1-propene, 1-
(2,4-dilauroyloxyphenyl) -3- (2-
Ethoxy-4-acetoxyphenyl) -3-hydroxy
-1-propene, 1- (2,4-dilauroyloxyf)
Enyl) -3- (2-ethoxy-4-lauroyloxy
Phenyl) -3-hydroxy-1-propene, 1-
(2,4-dilauroyloxyphenyl) -3- (2-
Methoxy-4-ethoxyphenyl) -3-hydroxy-
1-propene, 1- (2,4-dilauroyloxyphene)
Nil) -3- (2-methoxy-4-hydroxyphenyl)
1) -3-hydroxy-1-propene, 1- (2,4-
Dilauroyloxyphenyl) -3- (2-methoxy-
4-benzyloxyphenyl) -3-hydroxy-1-
Propene, 1- (2,4-dilauroyloxyphenyl)
) -3- (2-methoxy-4-acetoxyphenyl)
-3-hydroxy-1-propene, 1- (2,4-zilla)
Uroyloxyphenyl) -3- (2-methoxy-4-
Lauroyloxyphenyl) -3-hydroxy-1-prop
Lopen, 1- (2,4-dilauroyloxyphenyl)
-3- (2-Hydroxy-4-ethoxyphenyl) -3
-Hydroxy-1-propene, 1- (2,4-dilauro
Yloxyphenyl) -3- (2-hydroxy-4-me
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2,4-Dilauroyloxyphenyl) -3- (2
-Hydroxy-4-benzyloxyphenyl) -3-h
Droxy-1-propene, 1- (2,4-dilauroyl
Oxyphenyl) -3- (2-hydroxy-4-aceto
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dilauroyloxyphenyl) -3- (2-
(Hydroxy-4-lauroyloxyphenyl) -3-h
Droxy-1-propene, 1- (2,4-dilauroyl
Oxyphenyl) -3- (2-acetoxy-4-ethoxy)
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dilauroyloxyphenyl) -3- (2-
Acetoxy-4-methoxyphenyl) -3-hydroxy
-1-propene, 1- (2,4-dilauroyloxyf)
Enyl) -3- (2-acetoxy-4-benzyloxy)
Phenyl) -3-hydroxy-1-propene, 1-
(2,4-dilauroyloxyphenyl) -3- (2-
Acetoxy-4-hydroxyphenyl) -3-hydroxy
C-1-propene, 1- (2,4-dilauroyloxy)
Phenyl) -3- (2-acetoxy-4-lauroylo
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dilauroyloxyphenyl) -3- (2-
Lauroyloxy-4-ethoxyphenyl) -3-hydrido
Roxy-1-propene, 1- (2,4-dilauroylo
(Xyphenyl) -3- (2-lauroyloxy-4-me
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2,4-Dilauroyloxyphenyl) -3- (2
-Lauroyloxy-4-benzyloxyphenyl)-
3-hydroxy-1-propene, 1- (2,4-dilau)
Royloxyphenyl) -3- (2-lauroyloxy
-4-Hydroxyphenyl) -3-hydroxy-1-p
Lopen, 1- (2,4-dilauroyloxyphenyl)
-3- (2-Lauroyloxy-4-acetoxyphenyl)
1) -3-hydroxy-1-propene, 1- (2-dibe)
Benzyloxy-4-ethoxyphenyl) -3- (2-b
Ndyloxy-4-ethoxyphenyl) -3-hydroxy
C-1-propene, 1- (2-dibenzyloxy-4-
Ethoxyphenyl) -3- (2-benzyloxy-4-
Methoxyphenyl) -3-hydroxy-1-propene,
1- (2-dibenzyloxy-4-ethoxyphenyl)
-3- (2-benzyloxy-4-hydroxyphenyl)
1) -3-hydroxy-1-propene, 1- (2-dibe)
Benzyloxy-4-ethoxyphenyl) -3- (2-b
Ndyloxy-4-acetoxyphenyl) -3-hydro
Xy-1-propene, 1- (2-dibenzyloxy-4)
-Ethoxyphenyl) -3- (2-benzyloxy-4
-Lauroyloxyphenyl) -3-hydroxy-1-
Propene, 1- (2-dibenzyloxy-4-methoxy)
Phenyl) -3- (2-benzyloxy-4-ethoxy)
Phenyl) -3-hydroxy-1-propene, 1- (2
-Dibenzyloxy-4-methoxyphenyl) -3-
(2-benzyloxy-4-methoxyphenyl) -3-
Hydroxy-1-propene, 1- (2-dibenzyloxy)
C-4-methoxyphenyl) -3- (2-benzyloxy
(S-4-hydroxyphenyl) -3-hydroxy-1-
Propene, 1- (2-dibenzyloxy-4-methoxy)
Phenyl) -3- (2-benzyloxy-4-acetoxy
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2-dibenzyloxy-4-methoxyphenyl) -3
-(2-benzyloxy-4-lauroyloxyphenyl)
1) -3-hydroxy-1-propene, 1- (2-dibe)
Ndyloxy-4-hydroxyphenyl) -3- (2-
Benzyloxy-4-ethoxyphenyl) -3-hydro
Xy-1-propene, 1- (2-dibenzyloxy-4)
-Hydroxyphenyl) -3- (2-benzyloxy-
4-methoxyphenyl) -3-hydroxy-1-prope
1- (2-dibenzyloxy-4-hydroxyphene)
Nil) -3- (2-benzyloxy-4-hydroxyf
Enyl) -3-hydroxy-1-propene, 1- (2-
Dibenzyloxy-4-hydroxyphenyl) -3-
(2-benzyloxy-4-acetoxyphenyl) -3
-Hydroxy-1-propene, 1- (2-dibenzylo)
Xy-4-hydroxyphenyl) -3- (2-benzyl
Oxy-4-lauroyloxyphenyl) -3-hydro
Xy-1-propene, 1- (2-dibenzyloxy-4)
-Acetoxyphenyl) -3- (2-benzyloxy-
4-ethoxyphenyl) -3-hydroxy-1-prope
, 1- (2-dibenzyloxy-4-acetoxyfe
Nil) -3- (2-benzyloxy-4-methoxy)
Nyl) -3-hydroxy-1-propene, 1- (2-di
Benzyloxy-4-acetoxyphenyl) -3- (2
-Benzyloxy-4-hydroxyphenyl) -3-h
Droxy-1-propene, 1- (2-dibenzyloxy
-4-acetoxyphenyl) -3- (2-benzyloxy
C-4-acetoxyphenyl) -3-hydroxy-1-
Propene, 1- (2-dibenzyloxy-4-acetoxy)
(Ciphenyl) -3- (2-benzyloxy-4-lauro)
Yloxyphenyl) -3-hydroxy-1-prope
, 1- (2-dibenzyloxy-4-lauroyloxy)
(Ciphenyl) -3- (2-benzyloxy-4-ethoxy)
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2-dibenzyloxy-4-lauroyloxyphenyl
) -3- (2-benzyloxy-4-methoxyphenyl)
1) -3-hydroxy-1-propene, 1- (2-dibe)
Benzyloxy-4-lauroyloxyphenyl) -3-
(2-benzyloxy-4-hydroxyphenyl) -3
-Hydroxy-1-propene, 1- (2-dibenzylo)
Xy-4-lauroyloxyphenyl) -3- (2-b
Ndyloxy-4-acetoxyphenyl) -3-hydro
Xy-1-propene, 1- (2-dibenzyloxy-4)
-Lauroyloxyphenyl) -3- (2-benzylo)
(Xy-4-lauroyloxyphenyl) -3-hydroxy
Ci-1-propene, 1- (2-ethoxy-4-benzyl)
Oxyphenyl) -3- (2-benzyloxy-4-e
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2-ethoxy-4-benzyloxyphenyl) -3
-(2-benzyloxy-4-methoxyphenyl) -3
-Hydroxy-1-propene, 1- (2-ethoxy-4)
-Benzyloxyphenyl) -3- (2-benzyloxy
(S-4-hydroxyphenyl) -3-hydroxy-1-
Propene, 1- (2-ethoxy-4-benzyloxyf
Enyl) -3- (2-benzyloxy-4-acetoxy
Phenyl) -3-hydroxy-1-propene, 1- (2
-Ethoxy-4-benzyloxyphenyl) -3- (2
-Benzyloxy-4-lauroyloxyphenyl)-
3-hydroxy-1-propene, 1- (2-ethoxy-
4-methoxyphenyl) -3- (2-benzyloxy-
4-ethoxyphenyl) -3-hydroxy-1-prope
, 1- (2-ethoxy-4-methoxyphenyl) -3
-(2-benzyloxy-4-methoxyphenyl) -3
-Hydroxy-1-propene, 1- (2-ethoxy-4)
-Methoxyphenyl) -3- (2-benzyloxy-4
-Hydroxyphenyl) -3-hydroxy-1-prope
, 1- (2-ethoxy-4-methoxyphenyl) -3
-(2-benzyloxy-4-acetoxyphenyl)-
3-hydroxy-1-propene, 1- (2-ethoxy-
4-methoxyphenyl) -3- (2-benzyloxy-
4-lauroyloxyphenyl) -3-hydroxy-1
-Propene, 1- (2-ethoxy-4-hydroxyphene)
Nyl) -3- (2-benzyloxy-4-ethoxyfe
Nyl) -3-hydroxy-1-propene, 1- (2-e
Toxy-4-hydroxyphenyl) -3- (2-benzyl)
Ruoxy-4-methoxyphenyl) -3-hydroxy-
1-propene, 1- (2-ethoxy-4-hydroxyphenyl)
Enyl) -3- (2-benzyloxy-4-hydroxy
Phenyl) -3-hydroxy-1-propene, 1- (2
-Ethoxy-4-hydroxyphenyl) -3- (2-b
Ndyloxy-4-acetoxyphenyl) -3-hydro
Xy-1-propene, 1- (2-ethoxy-4-hydro
(Xyphenyl) -3- (2-benzyloxy-4-lau)
Royloxyphenyl) -3-hydroxy-1-prope
1- (2-ethoxy-4-acetoxyphenyl)-
3- (2-benzyloxy-4-ethoxyphenyl)-
3-hydroxy-1-propene, 1- (2-ethoxy-
4-acetoxyphenyl) -3- (2-benzyloxy
-4-methoxyphenyl) -3-hydroxy-1-pro
Pen, 1- (2-ethoxy-4-acetoxyphenyl)
-3- (2-benzyloxy-4-hydroxyphenyl)
L) -3-Hydroxy-1-propene, 1- (2-ethoxy)
Xy-4-acetoxyphenyl) -3- (2-benzyl
(Oxy-4-acetoxyphenyl) -3-hydroxy-
1-propene, 1- (2-ethoxy-4-acetoxyf
Enyl) -3- (2-benzyloxy-4-lauroyl
Oxyphenyl) -3-hydroxy-1-propene, 1
-(2-ethoxy-4-lauroyloxyphenyl)-
3- (2-benzyloxy-4-ethoxyphenyl)-
3-hydroxy-1-propene, 1- (2-ethoxy-
4-lauroyloxyphenyl) -3- (2-benzyl
Oxy-4-methoxyphenyl) -3-hydroxy-1
-Propene, 1- (2-ethoxy-4-lauroyloxy)
(Ciphenyl) -3- (2-benzyloxy-4-hydro
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2-ethoxy-4-lauroyloxyphenyl) -3
-(2-benzyloxy-4-acetoxyphenyl)-
3-hydroxy-1-propene, 1- (2-ethoxy-
4-lauroyloxyphenyl) -3- (2-benzyl
Oxy-4-lauroyloxyphenyl) -3-hydro
Xy-1-propene, 1- (2-methoxy-4-benzyl)
Ruoxyphenyl) -3- (2-benzyloxy-4-
Ethoxyphenyl) -3-hydroxy-1-propene,
1- (2-methoxy-4-benzyloxyphenyl)-
3- (2-benzyloxy-4-methoxyphenyl)-
3-hydroxy-1-propene, 1- (2-methoxy-
4-benzyloxyphenyl) -3- (2-benzylo
(Xy-4-hydroxyphenyl) -3-hydroxy-1
-Propene, 1- (2-methoxy-4-benzyloxy)
Phenyl) -3- (2-benzyloxy-4-acetoxy
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2-methoxy-4-benzyloxyphenyl) -3-
(2-benzyloxy-4-lauroyloxyphenyl
1) -3-hydroxy-1-propene, 1- (2-meth
Xy-4-ethoxyphenyl) -3- (2-benzylo)
(Xy-4-ethoxyphenyl) -3-hydroxy-1-
Propene, 1- (2-methoxy-4-ethoxyphenyl)
) -3- (2-benzyloxy-4-methoxyphenyl)
1) -3-hydroxy-1-propene, 1- (2-meth
Xy-4-ethoxyphenyl) -3- (2-benzylo)
(Xy-4-hydroxyphenyl) -3-hydroxy-1
-Propene, 1- (2-methoxy-4-ethoxyphenyl)
) -3- (2-Benzyloxy-4-acetoxyfe
Nyl) -3-hydroxy-1-propene, 1- (2-meth
Toxi-4-ethoxyphenyl) -3- (2-benzyl
Oxy-4-lauroyloxyphenyl) -3-hydro
Xy-1-propene, 1- (2-methoxy-4-hydro
(Xyphenyl) -3- (2-benzyloxy-4-ethoxy)
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2-methoxy-4-hydroxyphenyl) -3- (2
-Benzyloxy-4-methoxyphenyl) -3-hydrido
Roxy-1-propene, 1- (2-methoxy-4-hydride
Roxyphenyl) -3- (2-benzyloxy-4-hi
Droxyphenyl) -3-hydroxy-1-propene,
1- (2-methoxy-4-hydroxyphenyl) -3-
(2-benzyloxy-4-acetoxyphenyl) -3
-Hydroxy-1-propene, 1- (2-methoxy-4
-Hydroxyphenyl) -3- (2-benzyloxy-
4-lauroyloxyphenyl) -3-hydroxy-1
-Propene, 1- (2-methoxy-4-acetoxyfe)
Nyl) -3- (2-benzyloxy-4-ethoxyfe
Nyl) -3-hydroxy-1-propene, 1- (2-meth
Toxy-4-acetoxyphenyl) -3- (2-benzyl)
Ruoxy-4-methoxyphenyl) -3-hydroxy-
1-propene, 1- (2-methoxy-4-acetoxyf
Enyl) -3- (2-benzyloxy-4-hydroxy
Phenyl) -3-hydroxy-1-propene, 1- (2
-Methoxy-4-acetoxyphenyl) -3- (2-b
Ndyloxy-4-acetoxyphenyl) -3-hydro
Xy-1-propene, 1- (2-methoxy-4-aceto
(Xyphenyl) -3- (2-benzyloxy-4-lau)
Royloxyphenyl) -3-hydroxy-1-prope
, 1- (2-methoxy-4-lauroyloxyphenyl)
) -3- (2-benzyloxy-4-ethoxyphenyi)
1) -3-hydroxy-1-propene, 1- (2-meth
Xy-4-lauroyloxyphenyl) -3- (2-b
Ndyloxy-4-methoxyphenyl) -3-hydroxy
C-1-propene, 1- (2-methoxy-4-lauroy)
Ruoxyphenyl) -3- (2-benzyloxy-4-
(Hydroxyphenyl) -3-hydroxy-1-prope
, 1- (2-methoxy-4-lauroyloxyphenyl)
) -3- (2-Benzyloxy-4-acetoxyfe
Nyl) -3-hydroxy-1-propene, 1- (2-meth
Toxy-4-lauroyloxyphenyl) -3- (2-
Benzyloxy-4-lauroyloxyphenyl) -3
-Hydroxy-1-propene, 1- (2-hydroxy-
4-ethoxyphenyl) -3- (2-benzyloxy-
4-ethoxyphenyl) -3-hydroxy-1-prope
, 1- (2-hydroxy-4-ethoxyphenyl)-
3- (2-benzyloxy-4-methoxyphenyl)-
3-hydroxy-1-propene, 1- (2-hydroxy
-4-ethoxyphenyl) -3- (2-benzyloxy
-4-Hydroxyphenyl) -3-hydroxy-1-p
Lopen, 1- (2-hydroxy-4-ethoxyphenyl)
) -3- (2-Benzyloxy-4-acetoxyfe
Nyl) -3-hydroxy-1-propene, 1- (2-h
Droxy-4-ethoxyphenyl) -3- (2-benzyl)
Ruoxy-4-lauroyloxyphenyl) -3-hydrido
Roxy-1-propene, 1- (2-hydroxy-4-me
Toxiphenyl) -3- (2-benzyloxy-4-e
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2-hydroxy-4-methoxyphenyl) -3-
(2-benzyloxy-4-methoxyphenyl) -3-
Hydroxy-1-propene, 1- (2-hydroxy-4
-Methoxyphenyl) -3- (2-benzyloxy-4
-Hydroxyphenyl) -3-hydroxy-1-prope
, 1- (2-hydroxy-4-methoxyphenyl)-
3- (2-benzyloxy-4-acetoxyphenyl)
-3-Hydroxy-1-propene, 1- (2-hydroxy
C-4-methoxyphenyl) -3- (2-benzyloxy
Ci-4-lauroyloxyphenyl) -3-hydroxy
-1-propene, 1- (2-hydroxy-4-methoxy
Phenyl) -3- (2-benzyloxy-4-ethoxy)
Phenyl) -3-hydroxy-1-propene, 1- (2
-Hydroxy-4-methoxyphenyl) -3- (2-b
Ndyloxy-4-methoxyphenyl) -3-hydroxy
C-1-propene, 1- (2-hydroxy-4-methoxy)
(Ciphenyl) -3- (2-benzyloxy-4-hydro
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2-hydroxy-4-methoxyphenyl) -3- (2
-Benzyloxy-4-acetoxyphenyl) -3-h
Droxy-1-propene, 1- (2-hydroxy-4-
Methoxyphenyl) -3- (2-benzyloxy-4-
Lauroyloxyphenyl) -3-hydroxy-1-prop
Lopen, 1- (2-hydroxy-4-acetoxyphenyl)
) -3- (2-benzyloxy-4-ethoxyphenyi)
1) -3-hydroxy-1-propene, 1- (2-hydr)
Roxy-4-acetoxyphenyl) -3- (2-benzyl)
Ruoxy-4-methoxyphenyl) -3-hydroxy-
1-propene, 1- (2-hydroxy-4-acetoxy
Phenyl) -3- (2-benzyloxy-4-hydroxy
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2-hydroxy-4-acetoxyphenyl) -3-
(2-benzyloxy-4-acetoxyphenyl) -3
-Hydroxy-1-propene, 1- (2-hydroxy-
4-acetoxyphenyl) -3- (2-benzyloxy
-4-lauroyloxyphenyl) -3-hydroxy-
1-propene, 1- (2-hydroxy-4-lauroyl
Oxyphenyl) -3- (2-benzyloxy-4-e
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2-hydroxy-4-lauroyloxyphenyl)
-3- (2-benzyloxy-4-methoxyphenyl)
-3-Hydroxy-1-propene, 1- (2-hydroxy
Ci-4-lauroyloxyphenyl) -3- (2-ben
(Diloxy-4-hydroxyphenyl) -3-hydroxy
Ci-1-propene, 1- (2-hydroxy-4-lauro)
Yloxyphenyl) -3- (2-benzyloxy-4
-Acetoxyphenyl) -3-hydroxy-1-prope
1- (2-hydroxy-4-lauroyloxyphene)
Nil) -3- (2-benzyloxy-4-lauroylo
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2-acetoxy-4-ethoxyphenyl) -3- (2
-Benzyloxy-4-ethoxyphenyl) -3-hydrido
Roxy-1-propene, 1- (2-acetoxy-4-e
Toxiphenyl) -3- (2-benzyloxy-4-me
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2-acetoxy-4-ethoxyphenyl) -3-
(2-benzyloxy-4-hydroxyphenyl) -3
-Hydroxy-1-propene, 1- (2-acetoxy-
4-ethoxyphenyl) -3- (2-benzyloxy-
4-acetoxyphenyl) -3-hydroxy-1-pro
Pen, 1- (2-acetoxy-4-ethoxyphenyl)
-3- (2-benzyloxy-4-lauroyloxyf
Enyl) -3-hydroxy-1-propene, 1- (2-
Acetoxy-4-methoxyphenyl) -3- (2-ben
(Diloxy-4-ethoxyphenyl) -3-hydroxy
-1-propene, 1- (2-acetoxy-4-methoxy)
Phenyl) -3- (2-benzyloxy-4-methoxy
Phenyl) -3-hydroxy-1-propene, 1- (2
-Acetoxy-4-methoxyphenyl) -3- (2-b
Ndyloxy-4-hydroxyphenyl) -3-hydro
Xy-1-propene, 1- (2-acetoxy-4-methoate)
(Xyphenyl) -3- (2-benzyloxy-4-ace
Toxiphenyl) -3-hydroxy-1-propene, 1
-(2-acetoxy-4-methoxyphenyl) -3-
(2-benzyloxy-4-lauroyloxyphenyl
1) -3-hydroxy-1-propene, 1- (2-ace
Toxy-4-hydroxyphenyl) -3- (2-benzyl)
Ruoxy-4-ethoxyphenyl) -3-hydroxy-
1-propene, 1- (2-acetoxy-4-hydroxy
Phenyl) -3- (2-benzyloxy-4-methoxy
Phenyl) -3-hydroxy-1-propene, 1- (2
-Acetoxy-4-hydroxyphenyl) -3- (2-
Benzyloxy-4-hydroxyphenyl) -3-hydrido
Roxy-1-propene, 1- (2-acetoxy-4-h)
Droxyphenyl) -3- (2-benzyloxy-4-
(Acetoxyphenyl) -3-hydroxy-1-prope
1- (2-acetoxy-4-hydroxyphenyl)
-3- (2-benzyloxy-4-lauroyloxyf
Enyl) -3-hydroxy-1-propene, 1- (2-
Acetoxy-4-benzyloxyphenyl) -3- (2
-Benzyloxy-4-ethoxyphenyl) -3-hydrido
Roxy-1-propene, 1- (2-acetoxy-4-b)
Ndyloxyphenyl) -3- (2-benzyloxy-
4-methoxyphenyl) -3-hydroxy-1-prope
, 1- (2-acetoxy-4-benzyloxyphenyl)
) -3- (2-benzyloxy-4-hydroxyphene)
Nyl) -3-hydroxy-1-propene, 1- (2-a
Cetoxy-4-benzyloxyphenyl) -3- (2-
Benzyloxy-4-acetoxyphenyl) -3-hydrido
Roxy-1-propene, 1- (2-acetoxy-4-b)
Ndyloxyphenyl) -3- (2-benzyloxy-
4-lauroyloxyphenyl) -3-hydroxy-1
-Propene, 1- (2-acetoxy-4-lauroylo)
(Xyphenyl) -3- (2-benzyloxy-4-ethoxy)
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2-acetoxy-4-lauroyloxyphenyl)-
3- (2-benzyloxy-4-methoxyphenyl)-
3-hydroxy-1-propene, 1- (2-acetoxy
-4-lauroyloxyphenyl) -3- (2-benzyl)
Ruoxy-4-hydroxyphenyl) -3-hydroxy
-1-propene, 1- (2-acetoxy-4-lauroy
Ruoxyphenyl) -3- (2-benzyloxy-4-
(Acetoxyphenyl) -3-hydroxy-1-prope
1- (2-acetoxy-4-lauroyloxyphene)
Nil) -3- (2-benzyloxy-4-lauroylo
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2-Lauroyloxy-4-ethoxyphenyl) -3
-(2-benzyloxy-4-ethoxyphenyl) -3
-Hydroxy-1-propene, 1- (2-lauroylo
Kishi-4-ethoxyphenyl) -3- (2-benzylo)
(Xy-4-methoxyphenyl) -3-hydroxy-1-
Propene, 1- (2-lauroyloxy-4-ethoxy)
Phenyl) -3- (2-benzyloxy-4-hydroxy
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2-Lauroyloxy-4-ethoxyphenyl) -3
-(2-benzyloxy-4-acetoxyphenyl)-
3-hydroxy-1-propene, 1- (2-lauroyl
Oxy-4-ethoxyphenyl) -3- (2-benzyl
Oxy-4-lauroyloxyphenyl) -3-hydro
Xy-1-propene, 1- (2-lauroyloxy-4)
-Methoxyphenyl) -3- (2-benzyloxy-4
-Ethoxyphenyl) -3-hydroxy-1-prope
1- (2-lauroyloxy-4-methoxyphenyi)
) -3- (2-benzyloxy-4-methoxyphenyl)
1) -3-hydroxy-1-propene, 1- (2-lau)
Royloxy-4-methoxyphenyl) -3- (2-b
Ndyloxy-4-hydroxyphenyl) -3-hydro
Xy-1-propene, 1- (2-lauroyloxy-4)
-Methoxyphenyl) -3- (2-benzyloxy-4
-Acetoxyphenyl) -3-hydroxy-1-prope
1- (2-lauroyloxy-4-methoxyphenyi)
) -3- (2-benzyloxy-4-lauroyloxy)
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2-lauroyloxy-4-hydroxyphenyl)-
3- (2-benzyloxy-4-ethoxyphenyl)-
3-hydroxy-1-propene, 1- (2-lauroyl
Oxy-4-hydroxyphenyl) -3- (2-benzyl)
Ruoxy-4-methoxyphenyl) -3-hydroxy-
1-propene, 1- (2-lauroyloxy-4-hydride
Roxyphenyl) -3- (2-benzyloxy-4-hi
Droxyphenyl) -3-hydroxy-1-propene,
1- (2-lauroyloxy-4-hydroxyphenyl)
) -3- (2-Benzyloxy-4-acetoxyfe
Nyl) -3-hydroxy-1-propene, 1- (2-la
Uroyloxy-4-hydroxyphenyl) -3- (2
-Benzyloxy-4-lauroyloxyphenyl)-
3-hydroxy-1-propene, 1- (2-lauroyl
Oxy-4-benzyloxyphenyl) -3- (2-b
Ndyloxy-4-ethoxyphenyl) -3-hydroxy
C-1-propene, 1- (2-lauroyloxy-4-
Benzyloxyphenyl) -3- (2-benzyloxy
-4-methoxyphenyl) -3-hydroxy-1-pro
Pen, 1- (2-lauroyloxy-4-benzyloxy)
(Ciphenyl) -3- (2-benzyloxy-4-hydro
(Xyphenyl) -3-hydroxy-1-propene, 1-
(2-Lauroyloxy-4-benzyloxyphenyl)
) -3- (2-Benzyloxy-4-acetoxyfe
Nyl) -3-hydroxy-1-propene, 1- (2-la
Uroyloxy-4-benzyloxyphenyl) -3-
(2-benzyloxy-4-lauroyloxyphenyl
1) -3-hydroxy-1-propene, 1- (2-lau)
Royloxy-4-acetoxyphenyl) -3- (2-
Benzyloxy-4-ethoxyphenyl) -3-hydro
Xy-1-propene, 1- (2-lauroyloxy-4)
-Acetoxyphenyl) -3- (2-benzyloxy-
4-methoxyphenyl) -3-hydroxy-1-prope
, 1- (2-lauroyloxy-4-acetoxyfe
Nil) -3- (2-benzyloxy-4-hydroxyf
Enyl) -3-hydroxy-1-propene, 1- (2-
Lauroyloxy-4-acetoxyphenyl) -3-
(2-benzyloxy-4-acetoxyphenyl) -3
-Hydroxy-1-propene, 1- (2-lauroylo
Xy-4-acetoxyphenyl) -3- (2-benzyl
Oxy-4-lauroyloxyphenyl) -3-hydro
Xy-1-propene, 1- (2-benzyloxy-4-
Propenyloxyphenyl) -3- (2,4-diprope
Nyloxyphenyl) -3-hydroxy-1-prope
, 1- (2,4-dibenzyloxyphenyl) -3-
(2,4-dipropenyloxyphenyl) -3-hydro
Xy-1-propene, 1- (2-benzyloxy-4-
Methoxyphenyl) -3- (2,4-dipropenyloxy
(Cyphenyl) -3-hydroxy-1-propene, 1-
(2,4-dibenzyloxyphenyl) -3- (2-h
Droxy-4-propenyloxyphenyl) -3-hydride
Roxy-1-propene, 1- (2,4-dibenzyloxy)
(Ciphenyl) -3- (2-propenyloxy-4-hydride
Roxyphenyl) -3-hydroxy-1-propene, 1
-(2-benzyloxyphenyl-4-propenyloxy)
(Ciphenyl) -3- (2-propenyloxy-4-hydride
Roxyphenyl) -3-hydroxy-1-propene, 1
-(2-benzyloxyphenyl-4-propenyloxy)
(Ciphenyl) -3- (2,4-dibenzyloxyphenyl)
Ru) -3-hydroxy-1-propene and the like.
However, this is not the case. Even if these are used alone,
The above may be used in combination.

In the general formula (4) of the present invention, R ^{4 to} R ^4
7 is the same substituent as R ^{4 to} R ⁷ in the general formula (3), that is, the chalcone derivative represented by the general formula (4) corresponds to the hydrochalcone derivative represented by the general formula (3) Represents a compound.

In the present invention, the method for producing the chalcone derivative represented by the general formula (4) is not particularly limited.

[0028]

Embedded image (In the formula, R ^{4 to} R ⁵ represent the same substituent as R ^{4 to} R ⁵ in formula (4).)

A benzaldehyde derivative represented by the general formula (6)

[0030]

Embedded image (In the formula, R ^{6 to} R ⁷ represent the same substituent as R ^{6 to} R ⁷ in formula (4).)

Can be produced by subjecting the acetophenone derivative represented by the formula to aldol condensation in the presence of a base or an acid.

The method for producing the benzaldehyde derivative represented by the general formula (5) is not particularly limited.
In 4-dihydroxybenzaldehyde, a benzyl halide such as benzyl chloride or benzyl bromide or a p-type such as p-methoxybenzyl bromide in the presence of a base.
A method of reacting an alkyl halide such as methoxybenzyl halide and methyl iodide, a method of reacting an alkylating agent such as dimethyl sulfate, diethyl sulfate, isobutene, and trityl chloride, and a method of reacting a fatty acid halide such as acetyl chloride and lauroyl chloride. And a method of reacting an acid anhydride such as acetic anhydride and lauric anhydride. These may be used alone or in combination of two or more. The base to be used is not particularly limited, but specific examples thereof include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, and sodium hydroxide which are easy to handle. Examples thereof include alkali metal alcoholates such as methoxide, sodium ethoxide and potassium tert-butoxide, and organic bases such as triethylamine, pyridine, picoline and quinoline. These may be used alone or in combination of two or more. Absent.

The method for producing the acetophenone derivative represented by the general formula (6) is not particularly limited.
A method of reacting dihydroxyacetophenone with benzyl halide such as benzyl chloride or benzyl bromide or p-methoxybenzyl halide such as p-methoxybenzyl bromide or alkyl halide such as methyl iodide in the presence of a base, dimethyl sulfate, diethyl sulfate , Isobutene, a method of reacting an alkylating agent such as trityl chloride, etc., acetyl chloride, a method of reacting a fatty acid halide such as lauroyl chloride, acetic anhydride,
Examples thereof include a method of reacting an acid anhydride such as lauric anhydride. These may be used alone or in combination of two or more. The base used is not particularly limited, but specific examples include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide which are easy to handle,
Alkali metal carbonates such as sodium carbonate and potassium carbonate, sodium methoxide, sodium ethoxide, t
alkali metal alcoholates such as potassium tert-butoxy; and organic bases such as triethylamine, pyridine, picoline and quinoline.
A combination of more than one species may be used.

When a benzaldehyde derivative represented by the general formula (5) and an acetophenone derivative represented by the general formula (6) are subjected to aldol condensation to produce a chalcone derivative represented by the general formula (4), the compound is used as a catalyst. The base is not particularly limited, but is usually sodium hydroxide, an alkali metal hydroxide such as potassium hydroxide, sodium methoxide,
Alkali metal alcoholates such as sodium ethoxide and potassium tert-butoxide are used. The amount used depends on the reaction temperature, the reaction concentration, the type of the substituent, and the like, but is usually 5 to 200 mol% based on the raw material (benzaldehyde derivative or acetophenone derivative). If the amount is outside this range, the reaction rate is extremely slow or side reactions are accelerated.

When an acid is used as a catalyst, the kind of the acid is not particularly limited, but usually, hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, p-toluenesulfonic acid, trifluoromethanesulfonic acid and the like are used. . The amount used also varies depending on the reaction conditions and the like, but is usually 5 to 300 mol% based on the raw material (benzaldehyde derivative or acetophenone derivative). If the amount is outside this range, the reaction rate is extremely slow or side reactions are accelerated.

The reaction temperature at the time of the aldol condensation depends on the kind of the raw material, the kind of the catalyst and the amount of the catalyst, and is not particularly limited.
0 ° C. is preferred. At a reaction temperature outside this range, the reaction becomes extremely slow or side reactions cannot be suppressed.

The chalcone derivative represented by the general formula (4) obtained as described above may be used in the next step as a reaction solution or may be used after isolation. The isolation method is not particularly limited. For example, the isolation is performed by an operation such as concentration, recrystallization, or reprecipitation from the reaction solution. The isolated chalcone derivative may be used as it is as a wet cake to which a solvent is attached, or may be used after drying.

In the present invention, the hydrochalcone derivative represented by the general formula (3) can be produced by reducing the chalcone derivative represented by the general formula (4). Here, the term “reduction” means to convert a carbonyl group into a hydroxyl group as a functional group. The method of reduction is not particularly limited, but is usually performed by reacting a chalcone derivative dissolved or suspended in a solvent with a reducing agent.

The reducing agent to be used is not particularly limited.
Synthetic reaction generally used for reduction of carbonyl group to hydroxyl group
NaBH is a specific example.
_Four, NaBH_ThreeCN, NaBH (OCH_Three)_Three, NaBH_Two
S_ThreeSodium borohydride and its related compounds
Material, lithium borohydride, zinc borohydride,
Lithium dibutyl borohydride (LiBH (s-C
_FourH₉)_Three), LiAlH_Four, LiAlH (OCH_Three)_Three, L
iAlH (Ot-Bu)_Three, LiAlH_Four/ AlCl _Three
Aluminum hydride and its related compounds
Product, diisobutylaluminum hydride ((i-Bu)
_TwoAlH), diborane and its related compounds, SiH
(C_TwoH_Five)_Three, SiH_Two(C₆H_Five), C₆H_Five(CH_Three)_TwoS
Organosilicon compounds such as iH, SnH_Two(C₆H_Five)_Two, Sn
H_Two(N-Bu)_Two, SnH (n-Bu)_ThreeEtc. Organotin
Compounds, alkali metals-liquid ammonia (Birch return
Source), alkali metal-ethylamine or ethylene dia
And min (Benkeser reduction).

The solvent used for the reduction of the carbonyl group to the hydroxyl group is not particularly limited, and an organic solvent generally used in an organic synthesis reaction can be used as long as it is inert to the reaction. May be selected as appropriate. For example, in sodium borohydride system, a protic solvent such as alcohol, water, DMF and DMSO is preferable, and in lithium aluminum hydride system,
Ether solvents such as diethyl ether, THF, and diglyme are preferred. The reaction temperature at the time of the reduction reaction of the carbonyl group to the hydroxyl group depends on the reducing agent used, but is usually -5.
It is performed at about 0 ° C to 200 ° C. Although a catalyst may be required depending on the reducing agent used, there is no problem if it is appropriately selected and added.

The hydrochalcone derivative obtained by the above method can be used for the next catalytic hydrogenation reduction or the catalytic hydrogenation reduction and deprotection reaction as it is or after isolation. . Depending on the reducing agent used,
In some cases, treatment with water or alcohol is required after the reaction, but there is no problem if it is appropriately selected and added. The method of isolation is not particularly limited, and is a method in which crystallization is performed by concentration, recrystallization, reprecipitation with a poor solvent, or the like, and isolation is performed by a solid-liquid separation operation such as filtration, decanting, or centrifugation. In such a case, a method of isolating by distillation and the like can be mentioned. The crystals obtained by the solid-liquid separation may be used in the next step as a wet cake to which a solvent is attached, or may be used after drying after drying.

In the present invention, the hydrochalcone derivative represented by the general formula (3) is subjected to catalytic hydrogenation reduction or catalytic hydrogenation reduction and deprotection to convert the flavan derivative represented by the general formula (1). Can be manufactured.

The method of catalytic hydrogenation reduction is not particularly limited, but is usually carried out by contacting a chalcone derivative dissolved or suspended in a solvent with hydrogen in the presence of a catalyst. Hydrogen used for catalytic hydrogenation reduction may be introduced into the reaction system as hydrogen gas, or may be generated in the reaction system using ammonium formate or the like.

The catalyst used in the catalytic hydrogenation reduction is not particularly limited, but any catalyst that can be used in a general hydrogenation reaction can be used without any problem. Specific examples include platinum, palladium, ruthenium, rhodium and nickel catalysts. Although the amount of use is not particularly limited, it is usually 0.001 wt% to 100% based on the substrate.
About wt% is used. The reaction temperature at the time of the catalytic hydrogenation reduction is not particularly limited, and varies depending on the reaction pressure and the type of the catalyst. Outside this range, the reaction rate will be significantly slow or side reactions will be accelerated. The reaction pressure at the time of the catalytic hydrogenation reduction is not particularly limited, but usually, a normal pressure to a gauge pressure of 1 MPa is sufficient. At a gauge pressure higher than this, a side reaction may be promoted.

The solvent used in the catalytic hydrogenation reduction is
Any solvent generally used in organic synthesis reactions can be used without any problem. For example, water, methanol, ethanol,
Alcohols such as isopropanol, hydrocarbons such as hexane, cyclohexane, benzene, toluene xylene and mesitylene; And a cyclic ether such as a polar solvent, tetrahydrofuran and dioxane. These may be used alone or in combination of two or more.

After the catalytic hydrogenation reduction, the reaction solution may be used as it is in the next step or may be used as a solution in which the catalyst has been filtered off.
Alternatively, the catalyst may be used after isolation by filtration. The isolation method is not particularly limited, and examples thereof include a method of crystallization by concentration, recrystallization, reprecipitation with a poor solvent, and the like, and isolation by a solid-liquid separation operation such as filtration, decanting, or centrifugation. The isolated crystal may be used as it is as a wet cake to which a solvent is attached, or may be used after drying.

The deprotection reaction can be carried out according to a conventional method generally used for organic synthesis reactions. Here, the protecting group in the present invention means a protecting group of a hydroxyl group in the general formulas (1) and (3). For example, an alkyl ether-type protecting group can be obtained by treatment with boron tribromide, hydrogen bromide / acetic acid, trifluoroacetic acid or the like, and a trityl ether protecting group can be obtained by treatment with acetic acid, trifluoroacetic acid or the like. Further, since the protecting groups for benzyl ether and p-methoxybenzyl ether are removed by catalytic hydrogenation reduction, no special deprotection step is provided. For example, when all of the hydroxyl protecting groups in the general formula (3) are benzyl groups, 2- (2,4-dihydroxyphenyl) -7-hydroxychroman is produced by catalytic hydrogenation reduction.

In the present invention, selectivity can be imparted to deprotection by combining protective groups.
That is, when two or more kinds of protecting groups are used, a specific protecting group can be left as it is by selecting conditions for the deprotection reaction.

In the present invention, the formula (2)

Embedded image

An alkylating agent, an acylating agent and the like are allowed to act on 2- (2,4-dihydroxyphenyl) -7-hydroxychroman represented by the following formula to produce a flavan derivative represented by the general formula (1). Is also good. Examples of the alkylating agent include benzyl halides such as benzyl bromide and benzyl chloride, alkyl halides such as methyl chloride and methyl iodide, dimethyl sulfate, diethyl sulfate, isobutene, and trityl chloride. These may be used alone or in combination of two or more. Examples of the acylating agent include fatty acid halides such as acetyl chloride and lauroyl chloride; acid anhydrides such as acetic anhydride and lauric anhydride; and acetic acid and lauric acid using condensing agents such as dicyclohexylcarbodiimide. And a method of directly acting with a fatty acid.

The reaction temperature at this time is not particularly limited, and it is usually -20 to 200 ° C, preferably 0 to 150 ° C. Moreover, you may add a catalyst as needed. A base is usually used as a catalyst. Although the kind of the base is not particularly limited, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like can be used. An alkali metal alcoholate or the like is used.

The method for isolating the hydrochalcone derivative of the present invention is not particularly limited. However, usually, the reaction solution is crystallized by performing operations such as concentration, recrystallization, and reprecipitation, followed by filtration,
Isolation is performed by a solid-liquid separation operation such as decanting or centrifugation. The obtained crystals may be further subjected to purification operations such as column chromatography and recrystallization.

The cosmetic of the present invention can be blended with the flavan derivative represented by the general formula (1) alone or in combination of two or more. The blending amount is not particularly limited. 0.0001 wt% to 30 wt% of the composition,
Particularly, 0.001 wt% to 20 wt% is preferable. Within this range, the effect of the present invention is sufficient, the feel during use is good, and individual dosage forms can be kept stable.

The cosmetic of the present invention can be made into various dosage forms. According to a conventional method, lotions such as a soft lotion, an excretion lotion, a lotion for washing, an emollient emulsion, and a moisture emulsion. , Nourishing emulsions, emulsions such as cleansing emulsions, emollient creams, moisturizing creams, massage creams, creams such as cleansing creams, makeup creams, makeup such as lipsticks, foundations, etc. Is preferred.

The cosmetic of the present invention may contain any component other than the flavan derivative as long as the effects of the present invention are not impaired. For example, tar pigments, coloring pigments such as iron oxide, preservatives such as urea, methylparaben, ethylparapene, propylparapene, and sodium benzoate, fatty acid soaps, sodium cetyl sulfate, and N-stearoyl-L-
Anionic surfactants such as sodium glutamate, polyoxyethylene alkyl ethers, polyoxyethylene fatty acid esters, polyoxyethylene polyhydric alcohol fatty acid esters, polyoxyethylene hydrogenated castor oil, polyhydric alcohol fatty acid esters, polyglycerin fatty acid esters, etc. Nonionic surfactants, cationic surfactants such as tetraalkylammonium salts, betaine type, sulfobetaine type, amphoteric surfactants such as sulfoamino acid type, lecithin, natural surfactants such as lysophosphatidylcholine, Pigments such as titanium oxide, antioxidants such as dibutylhydroxytoluene, chelating agents, various vitamins, water, alcohol, ultraviolet absorbers, fragrances, oils, wetting agents, humectants, thickeners, various amino acids, various animal and plant extracts And the like. Furthermore, ascorbic acid, ascorbic acid derivatives, kojic acid, arbutin, hydrochalcone derivatives,
A whitening component such as a chalcone derivative can also be added. Cosmetics containing these components can be provided as medicinal cosmetics such as sunscreen cosmetics and skin protection cosmetics or quasi-drugs.

[0056]

EXAMPLES The present invention will be described below in detail with reference to examples, but the present invention is not limited to the examples.

The various test methods used in this example are as follows. (A) Tyrosinase activity inhibition test
1 ml of a tyrosine solution having a concentration of mg / ml and each sample solution containing 0.
9 ml was added, and the mixture was preliminarily kept at 37 ° C. for 10 minutes. To this was added 0.1 ml of tyrosinase (manufactured by Sigma) at a concentration of 1 mg / ml, and after heating at 37 ° C. for 15 minutes, the absorbance (A) was measured at a wavelength of 475 nm using a spectrophotometer. On the other hand, the absorbance (B) when 0.1 ml of buffer was added instead of tyrosinase, the absorbance (C) when 0.9 ml of buffer was added instead of the sample solution, and the buffer 1 was added instead of the sample solution and tyrosinase. The absorbance (D) of each of the samples to which 0.0 ml was added was measured, and the following formula was used.

[0058]

## EQU1 ## Inhibition rate (%) = [1- (AB) / (C-
D)] × 100

The inhibition rate (%) was calculated according to the following.

(B) Skin color brightness recovery test The skin on the inner part of the left and right upper arms of 20 subjects was continuously irradiated with 1.2 times the minimum erythema of UV-B in the UV-B region for 3 days, and one week after the first irradiation The reference lightness (Lo value, Lo ′) of the skin at two places of the sample application part of the example and the base application part of the comparative example
Value) was measured. Subsequently, the sample and the base were applied three times a day, and the skin lightness (Ln value, Ln ′ value) of the sample-applied part and the base-applied part skin were measured two and four weeks after the start of application. The recovery evaluation of the pigmented skin color was evaluated according to the criteria. The lightness of the skin was measured using a color difference meter (manufactured by Minolta Co., Ltd., type type CR-321). In addition, the evaluation was shown as an average value of the evaluation points of 4 subjects after 4 weeks.

[0061]

[Table 1]

(C) Practical skin whitening test The skin of the left forearm flexed side was exposed on the skin of the flexed side of the forearm of 20 subjects exposed to the sunlight of summer for 3 hours (1.5 hours a day for 2 days). From the day exposed to sunlight, the sample of the example, the right forearm flexion side skin from the day exposed to sunlight,
The base of the comparative example was applied once every morning and evening for eight weeks continuously.
In addition, evaluation was shown by the number of subjects who confirmed that the skin lightening effect of the sample application was stronger than that of the base application part.

(D) Optical Patch Test A closed patch was applied for 24 hours using a patch test patch having a diameter of 1.1 cm, to which 0.05 g of the sample of the example or the comparative example was applied to the skin of the flexed side of the forearm of 25 subjects. . After removing the bandage for patch test, let the summer sunshine
(3 hours a day for 2 days). In the evaluation, the skin condition of 25 subjects was evaluated and determined according to the criteria shown in Table 2. The judgment results were shown as (±) or more people 24 hours after the final irradiation.

[0064]

[Table 2]

(E) Storage stability test The samples of the examples and comparative examples were put in a thermostat at 45 ° C., and their changes with time were observed, and evaluated according to the criteria shown in Table 3. still,
The term “abnormal” means a phenomenon in which discoloration and odor occur, precipitation occurs in a lotion, and phase separation occurs in an emulsion.

[0066]

[Table 3]

Production Example 1 2,4-dihydroxybenzaldehyde (DHBA) 7
2.7 g (0.5 mol) are dissolved in 300 g of acetonitrile, 162.5 g (1.0 mol) of potassium carbonate is added, and 177.0 g of benzyl bromide (1.
0 mol) was added dropwise and reacted under reflux for 8 hours.
After filtering the reaction suspension, the filtrate was concentrated, and the precipitated crystals were filtered, washed, and dried to obtain 136.1 g of 2,4-dibenzyloxybenzaldehyde (DBBA). As a result of analysis by high performance liquid chromatography, the yield was 85.4.
% / DHBA.

Production Example 2 2,4-dihydroxyacetophenone (DHAP) 7
7.63 g (0.5 mol) of acetonitrile 300 g
And dissolved in potassium carbonate 162.6 g (1.0 mol)
And then add 177.0 g of benzyl bromide
(1.0 mol) was added dropwise and reacted under reflux for 8 hours. After filtering the reaction suspension, the filtrate was concentrated, and the precipitated crystals were filtered, washed, and dried to obtain 141.5 g of 2,4-dibenzyloxyacetophenone (DBAP). As a result of analysis by high performance liquid chromatography (HPLC), the yield in terms of purity was 85.2% / DHAP.

Production Example 3 67.0 g (0.20 mol) of DBBA obtained in Production Example 1
l) and 67.8 g of DBAP obtained in Production Example 2 (0.2
0 mol) is dissolved in 500 g of ethanol, and 20 wt%
Sodium ethoxide / ethanol solution 22.5g
(0.067 mol) and reacted at 50 ° C. for 30 hours. The reaction suspension was filtered, and the obtained wet body was washed with a small amount of cold ethanol, washed with water, dried, and dried.
3-bis (2,4-dibenzyloxyphenyl) -2-
124.8 g of yellow crystals of propen-1-one (TB-chalcone) were obtained. As a result of analysis by HPLC,
The purity conversion yield was 98.6%.

Example 1 TB-chalcone 32.60 obtained in Production Example 3
g (0.05 mol) in 235 g of THF was dropwise added with a solution of 3.36 g (0.08 mol) of 90 wt% sodium borohydride in 160 g of ethanol. Thereafter, the reaction was carried out at 45 ° C. for 13 hours. The raw material TB-chalcone had completely disappeared. Hexane was added to the obtained reaction solution to cause crystallization, and the obtained precipitate was filtered, washed with ethanol, washed with water, and dried to obtain 26.91 g of white crystals. ¹ H-NMR,
The structure was analyzed by H-H COZY NMR, IR and MS, and as a result, it was found to be 1,3-bis (2,4-dibenzyloxyphenyl) -3-hydroxy-1-propene. As a result of analysis by HPLC, the yield in terms of purity was 8
It was 4.5% / TB-chalcone. ¹ H-NMR [400 MHz, DMSO-d ₆ ] (Ph-
_{CH 2 -: 5.08ppm, Ph-} CH 2 -: 7.24~
7.45 ppm, -OH: 5.28 ppm, -CH-:
5.51 ppm, -CH = CH-: 6.25 ppm,
6.74 ppm, aromatic ring: 6.57 to 6.73 ppm,
7.27 to 7.32 ppm) IR [KBr tablet method] (-OH: 3449 cm ^-1 , 16)
^{10cm -1, 1504cm -1) MS [} EI method, FAB method] (m / z = 634,617)

Example 2 1,3-bis (2,4-dibenzyloxyphenyl) -3-hydroxy-1-propene obtained in Example 1
85 g (0.015 mol) was dissolved in 180 g of a THF / methanol mixed solvent, charged into a 500 ml autoclave, and 0.6 g of a 5 wt% Pd / C catalyst was added. / 2 hr. As a result of analysis by HPLC, the raw materials had completely disappeared. The catalyst was filtered off from the obtained reaction solution, and the filtrate was concentrated and allowed to stand overnight. Then, ethyl acetate / hexane = 2
Purification with a silica gel column was performed using a developing solution of / 1, and the obtained fraction was concentrated to dryness and dried to obtain pale yellow crystals. ¹ H-NMR, HH COZY NMR,
As a result of structural analysis by IR and MS, it was found to be 2- (2,4-dihydroxyphenyl) -7-hydroxychroman. The removal yield was 58.1%. ¹ H-NMR [400 MHz, DMSO-d ₆ ] (-O
H: 9.11 ppm, 9.22 ppm, 9.41 pp
_{m, -CH 2 -: 1.83~1.92ppm,} 1.98
-2.02 ppm, 2.55-2.59 ppm, 2.7
3-2.81 ppm, -CH-: 5.13 ppm, aromatic ring: 6.16 to 7.03 ppm) IR [KBr tablet method] (-OH: 3392 cm ^-1 , aromatic ring: 1612 cm ^-1 , 1510 cm ^-1 ) MS [EI method] (m / z = 258)

Examples 3 and 4 Using the 2- (2,4-dihydroxyphenyl) -7-hydroxychroman obtained in Example 2 as an active ingredient, a two-phase lotion was prepared using the composition shown in Table 4 and (A) ~
The test of (e) was performed. The compounding amount of the active ingredient 2- (2,4-dihydroxyphenyl) -7-hydroxychroman was 0.01 wt% (Example 3) and 0.2 wt% (Example 4).

(1) Adjustment method In the compounding amount shown in Table 4, 0.01 wt% or 0.20 wt% of component B is uniformly dissolved in component A, and the obtained solution and component C are uniformly mixed and stirred. It was dispersed and filled in a container to obtain a product. At the time of use, the content was shaken well and used evenly. (2) Characteristics Table 5 shows the results of various tests.

Comparative Example 1 In the operations of Examples 3 and 4, the active ingredient 2-
The above tests (a) to (e) were performed without blending (2,4-dihydroxyphenyl) -7-hydroxychroman. Table 5 shows the results.

[0075]

[Table 4]

[0076]

[Table 5]

Examples 5 to 6 In the raw material compositions shown in Table 6, 2-
(2,4-Dihydroxyphenyl) -7-hydroxychroman was blended as an active ingredient to prepare a skin cream, and the tests (a) to (e) were performed. The amount of the active ingredient 2- (2,4-dihydroxyphenyl) -7-hydroxychroman was 0.01 wt% (Example 5).
And 0.20 wt% (Example 6).

(1) Preparation method 0.01% and 0.20% by weight of component B shown in Table 4
The components were mixed and uniformly heated and dissolved to a temperature of 80 ° C. Next, the component C was poured into the component A, mixed with stirring, and then cooled to 30 ° C. with stirring to obtain a product. (2) Characteristics Table 7 shows the results of various tests.

Comparative Example 2 In the procedures of Examples 5 and 6, the active ingredient 2- (2,4-
Various tests were carried out without incorporating (dihydroxyphenyl) -7-hydroxychroman. Table 7 shows the results.

[0080]

[Table 6]

[0081]

[Table 7]

Examples 7 to 9 (Melanoma Cell Lightening Test) The melanin pigment synthesis inhibitory effect of each sample was measured by the change in cell color when B16 melanoma cells were cultured at a concentration that did not adversely affect cell proliferation.
B16 melanoma cells were placed in a 60 mm Petri dish at 1 × 105.
The seeds obtained in Production Example 2 were obtained 24 hours later.
(2,4-Dihydroxyphenyl) -7-hydroxychroman was added to the medium and cultured for 5 days. After the culture, the cells recovered by trypsinization were treated with 0.3 ml of phosphate buffer
After sonication, 0.3 ml of 4N-NaOH was added, and the mixture was incubated at 60 ° C. for 2 hours. The absorbance was measured at 400 nm.
The amount of released melanin when the content was set to 00% was calculated and is shown in Table 8. The amount of the active ingredient 2- (2,4-dihydroxyphenyl) -7-hydroxychroman added was 0.01 μm.
g / ml (Example 7), 0.03 μg / ml (Example 8), and 0.30 μg / ml (Example 9).

Comparative Examples 3 to 5 In the same manner as in Examples 7 to 9 except that dihydrophloretin, which is a kind of hydrochalcone, was used instead of 2- (2,4-dihydroxyphenyl) -7-hydroxychroman. Was performed. The results are shown in Table 8.

[0084]

[Table 8]

As shown in Tables 5 and 7, the flavan derivatives of the present invention showed clearly good results in all tests. In addition, no skin irritation occurred in various tests on human skin. Furthermore, as shown in Table 8, the flavan derivative of the present invention suppressed melanin release from B16 melanoma cells at a lower concentration than dihydrophloretin of Comparative Example.

[0086]

According to the present invention, a novel flavan derivative and a production method can be provided. In addition, the cosmetic containing the flavan derivative of the present invention as an active ingredient is excellent in the effect of inhibiting skin pigmentation due to ultraviolet rays, has the effect of rapidly reducing skin pigmentation, and has no skin irritation and is stored. Excellent stability.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (Reference) C07C 43/23 C07C 43/23 C F-term (Reference) 4C062 FF55 FF56 4C083 AA122 AC012 AC022 AC072 AC102 AC122 AC171 AC172 AC442 AC471 AC482 AC841 AC842 AD042 CC01 CC04 CC05 DD31 EE01 EE12 EE16 4H006 AA02 AC41 BE23 GP03 GP10

Claims (6)

[Claims] 1. A compound of the general formula (1) (Wherein R ^{1 to} R ³ are each independently a hydrogen atom,
Represents up to 20 linear or branched alkyl, alkenyl, and acyl groups, and an optionally substituted benzyl group. A flavan derivative represented by). 2. Formula (2) 2- (2,4-dihydroxyphenyl) -7 represented by
-Hydroxychroman. 3. A compound of the general formula (3) (Wherein R ^{4 to} R ⁷ are each independently a hydrogen atom,
Represents up to 20 linear or branched alkyl, alkenyl, and acyl groups, and an optionally substituted benzyl group. ). 4. A compound of the general formula (3) (Wherein R ^{4 to} R ⁷ are each independently a hydrogen atom,
Represents up to 20 linear or branched alkyl, alkenyl, and acyl groups, and an optionally substituted benzyl group. (1) wherein the hydrochalcone derivative represented by the formula (1) is subjected to catalytic hydrogenation reduction or catalytic hydrogenation reduction and deprotection. (Wherein R ^{1 to} R ³ are each independently a hydrogen atom,
Represents up to 20 linear or branched alkyl, alkenyl, and acyl groups, and an optionally substituted benzyl group. )). 5. A compound of the general formula (4) (Wherein R ^{4 to} R ⁷ are each independently a hydrogen atom,
Represents up to 20 linear or branched alkyl, alkenyl, and acyl groups, and an optionally substituted benzyl group. )) Reducing the chalcone derivative represented by the general formula (3): (Wherein R ^{4 to} R ⁷ are each independently a hydrogen atom,
Represents up to 20 linear or branched alkyl, alkenyl, and acyl groups, and an optionally substituted benzyl group. Method for producing hydrochalcone derivative represented by) 6. A cosmetic comprising the flavan derivative according to claim 1 as an active ingredient.