JP3144715B2 - Styryl ketone derivative, ultraviolet absorber using the same, and external preparation for skin containing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a styryl ketone derivative,
UV absorbers and skin external preparations, especially UV-A and UV-
The present invention relates to a styryl ketone derivative having an ultraviolet absorbing property in a region B, an ultraviolet absorbing agent and a skin external preparation using the same.

[0002]

2. Description of the Related Art Ultraviolet rays contained in sunlight are dermatologically long-wavelength ultraviolet rays (UV-320 nm).
A), medium wavelength ultraviolet light (UV-320 nm to 290 nm)
B) It is classified into a short wavelength ultraviolet ray (UV-C) of 290 nm or less. Among them, UV-C is absorbed by the ozone layer, and the ultraviolet rays reaching the ground surface are UV-A and UV-B. UV-A and UV-B, which are ultraviolet rays reaching the surface of the earth, have various effects on human skin. Among the ultraviolet rays, UV-A causes browning of the skin, promotes a decrease in skin elasticity and wrinkles, and causes rapid aging. On the other hand, UV-B forms erythema and blisters on the skin,
It also promotes melanin formation. Such UV-A and UV
Various UV absorbers have been developed to protect the skin from the harmful effects of -B.

[0003] As existing UV-A range ultraviolet absorbers, benzophenone derivatives, dibenzoylmethane derivatives, benzotriazole derivatives and the like have been used.
In addition, as an existing UV-B region ultraviolet absorber, PAB
A derivatives, cinnamic acid derivatives, salicylic acid derivatives, benzophenone derivatives, urocanine derivatives, camphor derivatives, heterocyclic derivatives and the like have been used. These UV absorbers are usually incorporated into skin external preparations such as cosmetics or quasi-drugs, and oil bases are widely used as external preparation bases. That is, since sunscreens are most frequently used in the summer, oil-based bases are used from the viewpoints of sweat resistance and water resistance, and those which have been used as ultraviolet absorbers are mostly oil-soluble. It was almost.

[0004]

However, recently, the influence of ultraviolet rays in daily life has become a problem, and sunscreen is desired even in ordinary skin care.
For this reason, a large amount of UV absorbers can be added to water-based skin care products such as lotions, and a large amount of UV absorbers can be added to the entire system even when formulating an external preparation having a higher UV absorption effect. Thus, it is desired to incorporate an ultraviolet absorber not only in the oil phase but also in the water phase, and there is a strong demand for the development of a water-soluble substance that absorbs ultraviolet rays in the UV-A and UV-B regions. Was. However, conventional UV
As described above, most of the absorbents are oil-soluble and have low water-solubility, and the formulation is limited. As a water-soluble UV absorber, only 2-hydroxy-4-methoxy-5-sulfoxonium benzophenone sodium salt is known, and since this is a salt, it affects the pH of the formulation system. There was a problem of bringing. The present invention has been made in view of the problems of the prior art, and its object is to provide an excellent U
An object of the present invention is to provide a substance which has VA and UV-B absorption and is water-soluble, and a skin external preparation containing the substance.

[0005]

Means for Solving the Problems As a result of intensive studies by the present inventors to achieve the above object, styryl ketone derivatives have excellent UV-A and UV-B absorption and are compatible with polar solvents. And completed the present invention. That is, in the present invention, the styryl ketone derivative according to claim 1 is represented by the following general formula 2.

Embedded image Here, R represents hydrogen, a hydroxyl group or an alkoxyl group, A represents a sugar alcohol, and G corresponds to 1 mol of glycerin. The ultraviolet absorbent according to claim 2 is an ultraviolet absorbent comprising the styryl ketone derivative of Chemical formula 2. The external preparation for skin according to claim 3 is characterized in that it contains one or more styryl ketone derivatives of the formula (2).

In the above general formula 2, R represents hydrogen, a hydroxyl group or an alkoxyl group. In the case of an alkoxyl group, the fatty chain may be any of a linear alkyl group, a branched alkyl group, an unsaturated alkyl group, and a cycloalkyl group, and specific examples of the fatty chain include a methyl group, an ethyl group,
Examples include acetylenyl, propyl, isopropyl, propenyl, butyl, isobutyl, t-butyl, and butenyl. In any case, there is no remarkable difference in the UV absorption wavelength, but from the industrial viewpoint, a methyl group and an ethyl group are particularly preferable.

A is a residue of a sugar alcohol. Specific examples of the sugar alcohol include sugar alcohols such as maltitol, sorbitol, mannitol, galactitol, glucitol, inositol, multitriol and the like. mixture, or more polysaccharides alcohols and their mixtures and the like, or Ru can also be used a mixture of these sugar alcohols. G is a glycerol group corresponding to 1 mole of glycerin, have such may be any bond adducted.

[0008] The above styryl ketone derivatives are solid or syrup-like and have excellent safety and stability.
In addition to being able to be blended with chemical products such as chemical fibers, it can be blended as a component of pharmaceuticals, quasi-drugs, cosmetics and cleaning agents. Further, it has a characteristic of having a moisturizing property. The styryl ketone derivative of the present invention is obtained by, for example, glycidylation of a hydroxystyryl ketone represented by the general formula (3), and the resulting glycidyloxystyryl ketone represented by the general formula (4).
Can be produced by reacting a sugar alcohol with a method described in Japanese Patent Application No. 61-180989.

Embedded image Here, R represents hydrogen, a hydroxyl group or an alkoxyl group.

Embedded image Here, R represents hydrogen, a hydroxyl group or an alkoxyl group. For example, they can be synthesized as follows.

The compound represented by the general formula (4) can be obtained by converting the compound represented by the general formula (3) by the method of Sandler et al.
ler, FRBerg, J.Appl.Polymer.Soc.9,3707 (1965)}
Robert et al. {Tetrhedorn, 35, 2169-2172 (1979)}
Can be synthesized by That is, dimethylsulfoxide, dimethylformamide, dioxane, dimethylacetamide, N-methylpyrrolidone, N-acetylmorpholine, dissolved or suspended in a non-aqueous solvent such as N-methylsuccinimide, or dissolved in an aqueous acetone solvent or The mixture may be suspended or stirred at 90 to 130 ° C. in the absence of a solvent and epichlorohydrin in the presence of a catalyst. At this time, the reaction may be carried out under a stream of nitrogen, argon, or the like. Or two or more of them may be used in combination.

At this time, the catalyst used is BF ₃ .Et ₂
O, Lewis acid catalyst such as aluminum trichloride, p-toluenesulfonic acid, heteropolyphosphoric acid, hydrochloric acid, acid catalyst such as sulfuric acid, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium hydride, sodium alcoholate, Examples thereof include alkalis such as sodium and amines such as N-methylbenzylamine. The compound represented by the general formula 2 can be obtained, for example, by converting the obtained compound represented by the general formula 4 into a sugar alcohol and Japanese Patent Application No. 61-18098.
No. 9 and the like. For example, Ru can be synthesized by the following method. A sugar alcohol is dissolved or suspended in a non-aqueous solvent such as dimethylsulfoxide, dimethylformamide, dioxane, dimethylacetamide, N-methylpyrrolidone, N-acetylmorpholine, N-methylsuccinimide, and represented by the general formula (4). The mixture is stirred at 90 to 130 ° C. under a compound and a catalyst. At this time, the reaction may be performed under an air current such as nitrogen or argon.
The compounds represented by Formula 4 may be used alone or in combination of two or more.

The catalyst used at this time is an acid catalyst such as p-toluenesulfonic acid, heteropolyphosphoric acid, hydrochloric acid, sulfuric acid, etc.
Examples thereof include alkalis such as sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium hydride, sodium alcoholate, and sodium, salts such as ammonium chloride and sodium chloride, and amines such as N-methylbenzylamine.

[0012] The molar ratio of the compound represented by the sugar alcohol and the general formalized 3 that is used in this reaction is, for example, in order to obtain a mono-ether as a main product, 1: 1
3: 1 are preferred, 2: 1 to 3: 1 is not further preferred.
If the molar ratio of the compound represented by the sugar alcohol and the general formalized 3 is out of this range, Chi words, the sugar alcohol is less prone to impurities such as tetra ether, if too large, remaining in large amounts sugar alcohols This is not preferred because it interferes with subsequent purification. When all the compounds represented by the general formula 3 are consumed, when an acid or an alkali is used as a catalyst, an acid such as acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid, or water for the purpose of neutralizing the catalyst of the reaction system. Add an alkali such as sodium oxide or potassium hydroxide. After these reactions, the reaction catalyst is distilled off under reduced pressure, and the product may be used as it is, may be used after being partitioned with a solvent or the like, or may be purified by a column chromatography method, a recrystallization method, or the like.

The reaction product thus obtained includes:
In addition to the styryl ketone derivative represented by the general formula 2,
Multimers, salts, and unreacted sugar alcohols coexist. If therefore, the removal of sugar alcohols and salts For example, methyl alcohol, ethyl alcohol, butyl alcohol,
It can be purified by extraction with a solvent such as isopropyl alcohol, or by partitioning between water containing a large amount of salt, methyl ethyl ketone and n-butanol, and separating the organic solvent layer. Ma
When the sugar alcohol and salt are removed and the compound is separated, the reaction product is suspended in water or a mixture of water and alcohol, and a hyperporous polymer (eg, a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.), octadecyl In a reversed-phase partition column such as silica, it can be purified by first passing through water, then passing through a mixed solution of water such as methanol or ethanol or a polar organic solvent such as acetonitrile and water, and separating this liquid. . Further, after removing the salt, it is also a purification child on a silica gel column Caro Mato graph method normal phase of.

The styryl ketone derivative thus obtained is excellent in chemical safety and oxidative stability, is water-soluble,
It has a function of absorbing moisture in the VA and UV-B regions and having excellent moisture retention. Since the styryl ketone derivative of the present invention is excellent in safety, it can be blended in cosmetics, pharmaceuticals and the like. In addition to the present invention, other commonly used cosmetic and pharmaceutical ingredients can be appropriately compounded. For example, liquid paraffin, squalane, petrolatum, cetyl alcohol, isostearyl alcohol, cetyl 2-ethylhexanoate, 2-octyldodecyl alcohol, glycerin triisostearate, macadamian nut oil, various hydrocarbons such as lanolin, oils and fats, wax Oils, silicones, surfactants, thickeners, neutralizers, preservatives, bactericides, antioxidants, powder components, pigments, fragrances, other ultraviolet absorbers, medicinal agents, metal blockers Agents, pH adjusters and the like.

[0015]

EXAMPLES Examples of the present invention will be described below, but they do not limit the technical scope of the present invention. The compounding amount is% by weight. Example 1 4- (4,4-Dimethyl-3-oxo-1-pentenyl) phenylglycero-luma
Lutitol ether t-butyl [2- (4-hydroxyphenyl) -ethenyl] ketone 2 g, epichlorohydrin 10.87 g,
After dissolving 0.025 ml of sodium hydroxide, 19.
6 mg was added, and the temperature of the reaction system was raised to 100 ° C.
C., and 4.50 g of sodium hydroxide was added, followed by heating and stirring for 3 hours. After cooling the system to room temperature,
The salt was removed by filtration. The obtained filtrate was concentrated under reduced pressure and purified by silica gel column chromatography to obtain 22 g (yield 86%) of solid t-butyl [2- (4-glycidyloxyphenyl) -ethenyl] ketone.

Next, 8.687 g of maltitol and 336.4 mg of sodium hydroxide were added to dimethyl sulfoxide 100.
After stirring under heating for 30 minutes under a nitrogen stream,
A solution obtained by dissolving 2.2 g of the obtained t-butyl [2- (4-glycidyloxyphenyl) -ethenyl] ketone in 20 ml of dimethyl sulfoxide was added dropwise. Furthermore, after heating and stirring for 1 hour under a nitrogen stream, the mixture was allowed to cool to room temperature and neutralized with hydrochloric acid. The reaction system was fractionated by column chromatography using a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.) using purified water as a developing solvent, and then using ethyl alcohol: purified water = 1: 1 as a developing solvent. The ethyl alcohol: purified water = 1: 1 eluate was concentrated to give 4-
2.9 g of (4,4-dimethyl-3-oxo-1-pentenyl) phenylglycerol maltitol ether was obtained. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
stretching vibration of glyceroyl group cm ^-1, the absorption due to the expansion and contraction motion of the carbonyl group 1690 cm ^-1 was observed. The results are shown in FIG. (2) ¹³ C-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When CD ₃ OD was dissolved and measured at 35 ° C.,
207ppm, 162ppm, 144ppm, 131p
pm, 129 ppm, 120 ppm, and 116 ppm, the signal derived from the carbon in the styryl ketone moiety was 101.
A signal derived from carbon in the glyceryl moiety and a signal derived from maltitol were observed at ppm to 62 ppm, respectively. The results are shown in FIG. (3) ¹ H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using CD ₃ OD as a solvent, δ
A signal derived from hydrogen in the styryl ketone portion was observed at 8 to 7 ppm, and a signal derived from hydrogen in the glyceryl portion and maltitol portion was observed at δ 5.8 to 3.5 ppm. The results are shown in FIG. (4) Ultraviolet absorption spectrum measurement method Using a UNIDEC 610C ultraviolet absorption spectrum measurement device manufactured by JASCO Corporation, measurement with a solvent methanol showed a maximum absorption at 323.0 nm. FIG. 4 shows the results. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown.

EXAMPLE 2 4- (4,4-Dimethyl-3-oxo-1-pentenyl)
Dissolve 2.3 g of phenylglycerol sorbitol ether sorbitol and 168 mg of sodium hydroxide in 60 ml of dimethyl sulfoxide,
After heating and stirring for 30 minutes, the t-butyl [2- (4-glycidyloxyphenyl) -ethenyl] obtained in Example 1 was obtained.
A solution of 1.1 g of ketone dissolved in 10 ml of dimethyl sulfoxide was added dropwise. Heating and stirring under a nitrogen stream
After performing the reaction for an hour, the mixture was allowed to cool to room temperature and neutralized with hydrochloric acid. After the reaction, purified water is first used as a developing solvent and then ethyl alcohol by column chromatography of a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.):
Fractionation was performed using purified water = 1: 1, and the eluted portion of ethyl alcohol: purified water = 1: 1 was concentrated to give 4- (4,4-dimethyl-3-oxo-1-pentenyl) phenylglycerol sorbitol ether. 1.1 g were obtained. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
stretching vibration of glyceroyl group cm ^-1, the absorption due to the expansion and contraction motion of the carbonyl group 1690 cm ^-1 was observed. (2) ¹³ C-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd., using CD ₃ OD as a solvent at 35 ° C., 207 ppm, 162 ppm, 144 ppm, 13 ppm
1 ppm, 129 ppm, 120 ppm, 116 pp
m, a signal derived from the carbon of the styryl ketone moiety was observed, and a signal derived from the carbon of the glyceryl moiety and a signal derived from sorbitol were observed from 101 ppm to 62 ppm. (3) ¹ H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using CD ₃ OD as a solvent, δ8
A signal derived from hydrogen in the styryl ketone portion was observed at ７7 ppm, and a signal derived from hydrogen in the glyceryl portion and sorbitol portion was observed at δ5.8 to 3.5 ppm. (4) Ultraviolet Absorption Spectrum Measurement Method When measured with a solvent methanol using a UVIDEC 610C ultraviolet absorption spectrum measurement device manufactured by JASCO Corporation, it showed a maximum absorption at 323.0 nm. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown.

EXAMPLE 3 4- (4,4-Dimethyl-3-oxo-1-pentenyl)
13.1 g of phenyl glycerol maltotriol ether maltotriol, sodium hydroxide 33
6.4 mg was dissolved in 100 ml of dimethyl sulfoxide, and the mixture was heated and stirred under a nitrogen stream for 30 minutes, and then 2.2 g of t-butyl [2- (4-glycidyloxyphenyl) -ethenyl] ketone obtained in Example 1 was obtained. Was dissolved in 20 ml of dimethyl sulfoxide. After heating and stirring for 1 hour under a nitrogen stream, the mixture was cooled to room temperature and neutralized with hydrochloric acid. The reaction system was fractionated by column chromatography using a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.) using purified water as a developing solvent, and then using ethyl alcohol: purified water = 1: 1 as a developing solvent. The ethyl alcohol: purified water = 1: 1 eluate was concentrated to give 4-
3.1 g of (4,4-dimethyl-3-oxo-1-pentenyl) phenylglycerol maltotriol ether
g was obtained. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
The stretching vibration of the glyceroyl group was observed at cm ^−1, and the absorption due to the stretching motion of the carbonyl group was observed at 1690 cm ⁻¹ . (2) ¹³ C-NMR measurement method JOEL GX-400 manufactured by JASCO Corporation, using CD ₃ OD as a solvent at 35 ° C., 207 ppm, 162 ppm, 144 ppm, 13 ppm
1 ppm, 129 ppm, 120 ppm, 116 ppm
Signal derived from the carbon of the styryl ketone moiety is 1
A signal derived from carbon in the glyceryl moiety and a signal derived from maltotriol were observed at 01 ppm to 62 ppm, respectively. (3) ¹ H-NMR measurement method When measured at room temperature with JOEL GX-400 manufactured by JASCO Corporation using CD ₃ OD as a solvent, a signal derived from hydrogen of the styryl ketone portion at δ 8 to 7 ppm was obtained. However, signals derived from hydrogen in the glyceryl moiety and the maltotriol moiety were observed at δ 5.8 to 3.5 ppm, respectively. (4) Ultraviolet absorber spectrum measurement method Using a UVIDEC 610C ultraviolet absorber spectrum measurement device manufactured by JASCO Corporation, when measured with a solvent methanol, it showed a maximum absorption at 323.0 nm. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown.

Example 4 2-methoxy-4- (4,4-dimethyl-3-oxo-1-
After dissolving 20 g of pentenyl) phenylglycerol maltitol ether t-butyl [2- (3-methoxy-4-hydroxyphenyl) -ethenyl] ketone and 93.1 g of epichlorohydrin, 169 mg of sodium hydroxide was added thereto. After the temperature of the system was raised to 100 ° C., the temperature was raised to 95 ° C., 3.86 g of sodium hydroxide was added, and the mixture was further heated and stirred for 3 hours. After cooling the system to room temperature, the salts were filtered off. The obtained filtrate was concentrated under reduced pressure,
When purified by silica gel column chromatography, solid t
23 g of -butyl [2- (3-methoxy-4-glycidyloxyphenyl) -ethenyl] ketone was obtained (yield 93%).

Next, 8.04 g of maltitol and 311 mg of sodium hydroxide were dissolved in 100 ml of dimethyl sulfoxide, and the mixture was heated and stirred for 30 minutes in a nitrogen stream, and the resulting t-butyl [2- (3-methoxy-4-) was obtained. A solution of 2.3 g of [glycidyloxyphenyl) -ethenyl] ketone dissolved in 20 ml of dimethyl sulfoxide was added dropwise. Furthermore, after heating and stirring for 1 hour under a nitrogen stream, the mixture was allowed to cool to room temperature and neutralized with hydrochloric acid. First, purified water was used as the developing solvent by column chromatography of a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.) as a developing solvent.
Next, fractionation was performed using ethyl alcohol: purified water = 1: 1, and the eluted portion of ethyl alcohol: purified water = 1: 1 was concentrated to give 2-methoxy-4- (4,4-dimethyl-3-oxo- 3.1 g of 1-pentenyl) phenylglycerol maltitol ether was obtained. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
stretching vibration of glyceroyl group cm ^-1, the absorption due to the expansion and contraction motion of the carbonyl group 1690 cm ^-1 was observed. (2) ¹³ C-NMR Measurement Method When measured at 35 ° C. using JOEL GX-400 manufactured by JEOL Ltd. using CD ₃ OD as a solvent, 207 ppm, 162 ppm, 144 ppm, 13
1 ppm, 129 ppm, 120 ppm, 116 ppm
Signal derived from the carbon of the styryl ketone moiety is 1
01 ppm to 62 ppm, the signal derived from the carbon of the glyceryl moiety and the signal derived from maltitol,
Each was observed. (3) ¹ H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using CD ₃ OD as a solvent, δ
A signal derived from hydrogen of the styryl ketone moiety was observed at 8 to 7 ppm, and a signal derived from hydrogen of the glyceryl moiety and maltitol moiety was observed at δ 5.8 to 3.5 ppm. (4) Ultraviolet Absorber Spectrum Measurement Method Using a UVIDEC 610C ultraviolet absorption spectrum measuring apparatus manufactured by JASCO Corporation, measurement with a solvent methanol showed a maximum absorption at 336.0 nm. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown.

Example 5 2-methoxy-4- (4,4-dimethyl-3-oxo-1-
(Pentenyl) phenyl glycerol maltotriol ether maltotriol 13.2 g, sodium hydroxide 311
mg was dissolved in 100 ml of dimethyl sulfoxide, and the mixture was heated and stirred under a nitrogen stream for 30 minutes, and then t-butyl [2- (3-methoxy-4-glycidyloxyphenyl) -ethenyl] ketone 2 obtained in Example 4 was obtained. A solution of 0.3 g dissolved in 20 ml of dimethyl sulfoxide was added dropwise. Furthermore, after heating and stirring for 1 hour under a nitrogen stream, the mixture was allowed to cool to room temperature and neutralized with hydrochloric acid. First, purified water was used as the developing solvent by column chromatography of a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.) as a developing solvent.
Next, fractionation was performed using ethyl alcohol: purified water = 1: 1, and the eluted portion of ethyl alcohol: purified water = 1: 1 was concentrated to give 2-methoxy-4- (4,4-dimethyl-3-oxo-1). 3.2 g of -pentenyl) phenylglycerol maltotriol ether were obtained. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
stretching vibration of glyceroyl group cm ^-1, the absorption due to the expansion and contraction motion of the carbonyl group 1690 cm ^-1 was observed. (2) ¹³ C-NMR Measurement Method When measured at 35 ° C. using JOEL GX-400 manufactured by JEOL Ltd. using CD ₃ OD as a solvent, 207 ppm, 162 ppm, 144 ppm, 13
1 ppm, 129 ppm, 120 ppm, 116 ppm
Signal derived from the carbon of the styryl ketone moiety
From 01 ppm to 62 ppm, a signal derived from carbon in the glyceryl moiety and a signal derived from maltotriol were respectively observed. (3) ¹ H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using CD ₃ OD as a solvent, δ
A signal derived from hydrogen in the styryl ketone portion was observed at 8 to 7 ppm, and a signal derived from hydrogen in the glyceryl portion and maltotriol portion was observed at δ 5.8 to 3.5 ppm. (4) Ultraviolet Absorber Spectrum Measurement Method Using a UVIDEC 610C ultraviolet absorption spectrum measuring apparatus manufactured by JASCO Corporation, measurement with a solvent methanol showed a maximum absorption at 336.0 nm. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown.

Example 6 2-methoxy-4- (4,4-dimethyl-3-oxo-1-
(Pentenyl) phenylglycerol sorbitol ether sorbitol (4.4 g) and sodium hydroxide (311 mg) were dissolved in dimethyl sulfoxide (60 ml).
After heating and stirring for 30 minutes, a solution prepared by dissolving 2.3 g of t-butyl [2- (3-methoxy-4-glycidyloxyphenyl) -ethenyl] ketone obtained in Example 4 in 10 ml of dimethyl sulfoxide was added dropwise. . Furthermore, after heating and stirring for 1 hour under a nitrogen stream, the mixture was allowed to cool to room temperature and neutralized with hydrochloric acid. The reaction system was fractionated by column chromatography using a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.) using purified water as a developing solvent, and then using ethyl alcohol: purified water = 1: 1 as a developing solvent. The eluted portion of ethyl alcohol: purified water = 1: 1 was concentrated to obtain 1.8 g of 2-methoxy-4- (4,4-dimethyl-3-oxo-1-pentenyl) phenylglycerol sorbitol ether. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
stretching vibration of glyceroyl group cm ^-1, the absorption due to the expansion and contraction motion of the carbonyl group 1690 cm ^-1 was observed. (2) ¹³ C-NMR Measurement Method When measured at 35 ° C. using JOEL GX-400 manufactured by JEOL Ltd. using CD ₃ OD as a solvent, 207 ppm, 162 ppm, 144 ppm, 13
1 ppm, 129 ppm, 120 ppm, 116 ppm
Signal derived from the carbon of the styryl ketone moiety is 1
A signal derived from carbon in the glyceryl moiety and a signal derived from sorbitol were observed at 01 ppm to 62 ppm, respectively. (3) ¹ H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using CD ₃ OD as a solvent, δ
A signal derived from hydrogen in the styryl ketone portion was observed at 8 to 7 ppm, and a signal derived from hydrogen in the glyceryl portion and sorbitol portion was observed at δ 5.8 to 3.5 ppm. (4) Ultraviolet Absorber Spectrum Measurement Method Using a UVIDEC 610C ultraviolet absorption spectrum measuring apparatus manufactured by JASCO Corporation, measurement with a solvent methanol showed a maximum absorption at 336.0 nm. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown.

Example 7 2,6-Dimethoxy-4- (4,4-dimethyl-3-oxo
After dissolving 20 g of so-1-pentenyl) phenylglycerol maltitol ether t-butyl [2- (3,5-dimethoxy-4-hydroxyphenyl) -ethenyl] ketone, 8.15 g of epichlorohydrin, and 0.025 ml of hydroxylation, 147 mg of sodium was added, the temperature of the reaction system was raised to 100 ° C., the temperature was raised to 95 ° C., 3.3 g of sodium hydroxide was added, and the mixture was further heated and stirred for 3 hours. After cooling the system to room temperature, the salts were filtered off. The obtained filtrate was concentrated under reduced pressure and purified by silica gel column chromatography.
Solid t-butyl [2- (3,5-dimethoxy-4-
Glycidyloxyphenyl) -ethenyl] ketone 20 g
(82% yield).

Then, 6.27 g of maltitol and 242 mg of sodium hydroxide were dissolved in 100 ml of dimethyl sulfoxide, and the mixture was heated and stirred for 30 minutes under a nitrogen stream, and then the resulting t-butyl [2- (3,5-dimethoxy-) was obtained. A solution of 2.0 g of 4-glycidyloxyphenyl) -ethenyl] ketone dissolved in 20 ml of dimethyl sulfoxide was added dropwise.
Furthermore, after heating and stirring for 1 hour under a nitrogen stream, the mixture was allowed to cool to room temperature and neutralized with hydrochloric acid. The reaction system was fractionated by column chromatography using a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.) using purified water as a developing solvent, and then using ethyl alcohol: purified water = 1: 1 as a developing solvent. The eluted part of ethyl alcohol: purified water = 1: 1 was concentrated to obtain 2.5 g of 2,6-dimethoxy-4- (4,4-dimethyl-3-oxo-1-pentenyl) phenylglycerol maltitol ether. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
stretching vibration of glyceroyl group cm ^-1, the absorption due to the expansion and contraction motion of the carbonyl group 1690 cm ^-1 was observed. (2) ¹³ C-NMR Measurement Method When measured at 35 ° C. using JOEL GX-400 manufactured by JEOL Ltd. using CD ₃ OD as a solvent, 207 ppm, 162 ppm, 144 ppm, 13
1 ppm, 129 ppm, 120 ppm, 116 pp
m, a signal derived from the carbon of the styryl ketone portion was observed, and a signal derived from the carbon of the glyceryl portion and a signal derived from maltitol were observed at 101 ppm to 62 ppm, respectively. (3) ¹ H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using CD ₃ OD as a solvent, δ
A signal derived from hydrogen in the styryl ketone portion was observed at 8 to 7 ppm, and a signal derived from hydrogen in the glyceryl portion and maltitol portion was observed at δ 5.8 to 3.5 ppm. (4) Ultraviolet Absorber Spectrum Measurement Method Using a UVIDEC 610C ultraviolet absorption spectrum measurement device manufactured by JASCO Corporation, the maximum absorption was shown at 323.0 nm when measured with a solvent methanol. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown.

Example 8 2,6-dimethoxy-4- (4,4-dimethyl-3-oxo
Dissolve 3.1 g of ( so-1-pentenyl) phenylglycerol sorbitol ether sorbitol and 242 mg of sodium hydroxide in 60 ml of dimethyl sulfoxide,
After heating and stirring for 30 minutes, 2.0 g of the t-butyl [2- (3,5-dimethoxy-4-glycidyloxyphenyl) -ethenyl] ketone obtained in Example 7 was dissolved in 10 ml of dimethyl sulfoxide. It was dropped. Furthermore, after heating and stirring for 1 hour under a nitrogen stream, the mixture was allowed to cool to room temperature and neutralized with hydrochloric acid. First, purified water was used as the developing solvent by column chromatography of a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.) as a developing solvent.
Next, fractionation was performed using ethyl alcohol: purified water = 1: 1, and the eluted portion of ethyl alcohol: purified water = 1: 1 was concentrated to give 2,6-dimethoxy-4- (4,4-dimethyl-3).
2.8 g of-(oxo-1-pentenyl) phenylglycerol sorbitol ether was obtained. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
stretching vibration of glyceroyl group cm ^-1, the absorption due to the expansion and contraction motion of the carbonyl group 1690 cm ^-1 was observed. (2) ¹³ C-NMR Measurement Method When measured at 35 ° C. using JOEL GX-400 manufactured by JEOL Ltd. with CD ₃ OD as a solvent, 207 ppm, 162 ppm, 144 ppm, 13
1 ppm, 129 ppm, 120 ppm, 116 ppm
Signal derived from the carbon of the styryl ketone moiety is 1
A signal derived from carbon in the glyceryl moiety and a signal derived from sorbitol were observed at 01 ppm to 62 ppm, respectively. (3) ¹ H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using CD ₃ OD as a solvent, δ
A signal derived from hydrogen in the styryl ketone portion was observed at 8 to 7 ppm, and a signal derived from hydrogen in the glyceryl portion and sorbitol portion was observed at δ 5.8 to 3.5 ppm. (4) Ultraviolet Absorber Spectrum Measurement Method Using a UVIDEC 610C ultraviolet absorption spectrum measurement device manufactured by JASCO Corporation, measurement with a solvent methanol showed a maximum absorption at 323.0 nm. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown.

Example 9 2,6-dimethoxy-4- (4,4-dimethyl-3-oxo
(So-1-pentenyl) phenylglycerol maltotriol ether , then 9.4 g of multitriol , sodium hydroxide 33
6.4 mg was dissolved in 100 ml of dimethyl sulfoxide, and the mixture was stirred with heating under a nitrogen stream for 30 minutes, and then the t-butyl [2- (3,5-dimethoxy-4-) obtained in Example 7 was obtained.
Glycidyloxyphenyl) -ethenyl] ketone 2.0 g
Was dissolved in 20 ml of dimethyl sulfoxide. Furthermore, after heating and stirring for 1 hour under a nitrogen stream, the mixture was allowed to cool to room temperature and neutralized with hydrochloric acid. The reaction system was first purified water, then ethyl alcohol: purified water = 1: as a developing solvent by column chromatography of a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.).
1 using ethyl alcohol: purified water = 1: 1
The eluted part was concentrated and 2,6-dimethoxy-4- (4,4-
2.1 g of dimethyl-3-oxo-1-pentenyl) phenylglycerol maltotriol ether was obtained. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
stretching vibration of glyceroyl group cm ^-1, the absorption due to the expansion and contraction motion of the carbonyl group 1690 cm ^-1 was observed. (2) ¹³ C-NMR Measurement Method When measured at 35 ° C. using JOEL GX-400 manufactured by JEOL Ltd. using CD ₃ OD as a solvent, 207 ppm, 162 ppm, 144 ppm, 13
1 ppm, 129 ppm, 120 ppm, 116 ppm
Signal derived from the carbon of the styryl ketone moiety is 1
From 01 ppm to 62 ppm, a signal derived from carbon in the glyceryl moiety and a signal derived from maltotriol were respectively observed. (3) ¹ H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using CD ₃ OD as a solvent, δ
A signal derived from hydrogen in the styryl ketone portion was observed at 8 to 7 ppm, and a signal derived from hydrogen in the glyceryl portion and maltotriol portion was observed at δ 5.8 to 3.5 ppm. (4) Ultraviolet Absorber Spectrum Measurement Method Using a UVIDEC 610C ultraviolet absorption spectrum measurement device manufactured by JASCO Corporation, the maximum absorption was shown at 323.0 nm when measured with a solvent methanol. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown.

Example 10 4- (4,4-Dimethyl-3-oxo-1-pentenyl)
) -6-methoxy -phenyl glycerol sorbitol ether t-butyl [2- (4-hydroxy-5-methoxyphenyl) -ethenyl ] ketone 20 g, epichlorohydrin 9
After dissolving 3.1 g and 0.025 ml, 169 mg of sodium hydroxide was added, the temperature of the reaction system was raised to 100 ° C., the temperature was raised to 95 ° C., 3.86 g of sodium hydroxide was added, and the mixture was further heated and stirred for 3 hours. Done. After allowing the system to cool to room temperature, the salts were filtered off. The obtained filtrate was concentrated under reduced pressure,
When purified by silica gel column chromatography, 22 g of solid t-butyl [2- (4-glycidyloxy-5-methoxy-phenyl) -ethenyl] ketone was obtained (absorption rate: 88
%) Obtained.

Next, 4.2 g of sorbitol and 297 mg of sodium hydroxide were dissolved in 60 ml of dimethyl sulfoxide, and the mixture was heated and stirred under a nitrogen stream for 30 minutes.
A solution of 2.2 g of -butyl [2- (4-glycidyloxy5-methoxy-phenyl) -ethenyl] ketone in 10 ml of dimethyl sulfoxide was added dropwise. Furthermore, after heating and stirring for 1 hour under a nitrogen stream, the mixture was allowed to cool to room temperature and neutralized with hydrochloric acid. First, purified water was used as the developing solvent by column chromatography of a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.) as a developing solvent.
Next, fractionation was performed using ethyl alcohol: purified water = 1: 1, and the eluted portion of ethyl alcohol: purified water = 1: 1 was concentrated to give 4- (4,4-dimethyl-3-oxo-1-pentenyl). 1.9 g of -6-methoxy-phenylglycerol sorbitol ether was obtained. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
stretching vibration of glyceroyl group cm ^-1, the absorption due to the expansion and contraction motion of the carbonyl group 1690 cm ^-1 was observed. (2) ¹³ C-NMR Measurement Method When measured at 35 ° C. using JOEL GX-400 manufactured by JEOL Ltd. using CD ₃ OD as a solvent, 207 ppm, 162 ppm, 144 ppm, 13
1 ppm, 129 ppm, 120 ppm, 116 ppm
Signal derived from the carbon of the styryl ketone moiety is 1
A signal derived from carbon in the glyceryl moiety and a signal derived from sorbitol were observed at 01 ppm to 62 ppm, respectively. (3) ¹ H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using CD ₃ OD as a solvent, δ
A signal derived from hydrogen in the styryl ketone portion was observed at 8 to 7 ppm, and a signal derived from hydrogen in the glyceryl portion and sorbitol portion was observed at δ 5.8 to 3.5 ppm. (4) Ultraviolet Absorber Spectrum Measurement Method Using a UVIDEC 610C ultraviolet absorption spectrum measurement device manufactured by JASCO Corporation, the maximum absorption was shown at 323.0 nm when measured with a solvent methanol. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown.

Example 11 6-Methoxy-4- (4,4-dimethyl-3-oxo-
1-pentenyl) phenyl glycerol maltotriol ether maltotriol 12.6 g, sodium hydroxide 297
mg was dissolved in 100 ml of dimethyl sulfoxide, and the mixture was heated and stirred under a nitrogen stream for 30 minutes, and then the t-butyl [2- (5-methoxy-4-glycidyloxyphenyl) -ethenyl] ketone 2 obtained in Example 10 was obtained. A solution of 0.2 g dissolved in 20 ml of dimethyl sulfoxide was added dropwise. Furthermore, after heating and stirring for 1 hour under a nitrogen stream, the mixture was allowed to cool to room temperature and neutralized with hydrochloric acid. The reaction system was fractionated by column chromatography using a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.) using purified water as a developing solvent, and then using ethyl alcohol: purified water = 1: 1 as a developing solvent. The eluted part of ethyl alcohol: purified water = 1: 1 was concentrated to obtain 2.2 g of 6-, methoxy 4- (4,4-dimethyl-3-oxo-1-pentenyl) phenylglycerol maltotriol ether. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
stretching vibration of glyceroyl group cm ^-1, the absorption due to the expansion and contraction motion of the carbonyl group 1690 cm ^-1 was observed. (2) ¹³ C-NMR Measurement Method When measured at 35 ° C. using JOEL GX-400 manufactured by JEOL Ltd. using CD ₃ OD as a solvent, 207 ppm, 162 ppm, 144 ppm, 13
1 ppm, 129 ppm, 120 ppm, 116 ppm
Signal derived from the carbon of the styryl ketone moiety is 1
From 01 ppm to 62 ppm, a signal derived from carbon in the glyceryl moiety and a signal derived from maltotriol were respectively observed. (3) ¹ H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using CD ₃ OD as a solvent, δ
A signal derived from hydrogen in the styryl ketone portion was observed at 8 to 7 ppm, and a signal derived from hydrogen in the glyceryl portion and maltotriol portion was observed at δ 5.8 to 3.5 ppm. (4) Ultraviolet Absorber Spectrum Measurement Method Using a UVIDEC 610C ultraviolet absorption spectrum measurement device manufactured by JASCO Corporation, the maximum absorption was shown at 323.0 nm when measured with a solvent methanol. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown.

Example 12 6-Methoxy-4- (4,4-dimethyl-3-oxo-
8.45 g of 1-pentenyl) phenylglycerol maltitol ether maltitol, 297 mg of sodium hydroxide
Was dissolved in 100 ml of dimethyl sulfoxide, and the mixture was heated and stirred under a nitrogen stream for 30 minutes.
A solution of 2.2 g of -butyl [2- (5-methoxy-4-glycidyloxyphenyl) -ethenyl] ketone in 20 ml of dimethyl sulfoxide was added dropwise. Furthermore, after heating and stirring for 1 hour under a nitrogen stream, the mixture was allowed to cool to room temperature and neutralized with hydrochloric acid. First, purified water was used as the developing solvent by column chromatography of a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.) as a developing solvent.
Next, fractionation was performed using ethyl alcohol: purified water = 1: 1, and the eluted portion of ethyl alcohol: purified water = 1: 1 was concentrated to give 6-methoxy-4- (4,4-dimethyl-3-oxo- 3.1 g of 1-pentenyl) phenylglycerol maltitol ether was obtained. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
stretching vibration of glyceroyl group cm ^-1, the absorption due to the expansion and contraction motion of the carbonyl group 1690 cm ^-1 was observed. (2) ¹³ C-NMR Measurement Method When measured at 35 ° C. using JOEL GX-400 manufactured by JEOL Ltd. using CD ₃ OD as a solvent, 207 ppm, 162 ppm, 144 ppm, 13
1 ppm, 129 ppm, 120 ppm, 116 ppm
Signal derived from the carbon of the styryl ketone moiety is 1
A signal derived from carbon in the glyceryl moiety and a signal derived from maltitol were observed at 01 ppm to 62 ppm, respectively. (3) ¹ H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using CD ₃ OD as a solvent, δ
A signal derived from hydrogen in the styryl ketone portion was observed at 8 to 7 ppm, and a signal derived from hydrogen in the glyceryl portion and maltitol portion was observed at δ 5.8 to 3.5 ppm. (4) Ultraviolet Absorber Spectrum Measurement Method Using a UVIDEC 610C ultraviolet absorption spectrum measurement device manufactured by JASCO Corporation, the maximum absorption was shown at 323.0 nm when measured with a solvent methanol. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown.

Example 13 6-Methoxy-3- (4,4-dimethyl-3-oxo-
After dissolving 20 g of 1-pentenyl) phenylglycerol sorbitol ether t-butyl [2- (4-methoxy-5-hydroxyphenyl) -ethenyl] ketone, 93.1 g of epichlorohydrin, and 0.025 ml, 169 mg of sodium hydroxide was added. After the temperature of the reaction system was raised to 100 ° C., the temperature was raised to 95 ° C., 3.86 g of sodium hydroxide was added, and the mixture was further heated and stirred for 3 hours. After cooling the system to room temperature, the salts were filtered off. The obtained filtrate was concentrated under reduced pressure,
When purified by silica gel column chromatography, solid t
As a result, 21 g (yield: 85%) of -butyl [2- (4-methoxy-5-glycidyloxyphenyl) -ethenyl] ketone was obtained.

Next, 4.0 g of sorbitol and 283 mg of sodium hydroxide were dissolved in 60 ml of dimethyl sulfoxide, and the mixture was heated and stirred for 30 minutes under a nitrogen stream.
A solution of 2.1 g of -butyl [2- (4-methoxy-5-glycidyloxyphenyl) -ethenyl] ketone dissolved in 20 ml of dimethyl sulfoxide was added dropwise. Furthermore, after heating and stirring for 1 hour under a nitrogen stream, the mixture was allowed to cool to room temperature and neutralized with hydrochloric acid. First, purified water was used as the developing solvent by column chromatography of a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.) as a developing solvent.
Next, fractionation was performed using ethyl alcohol: purified water = 1: 1, and the eluted portion of ethyl alcohol: purified water = 1: 1 was concentrated to give 6-methoxy-3- (4,4-dimethyl-3-oxo-). 1.7 g of 1-pentenyl) phenylglycerol sorbitol ether was obtained. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
stretching vibration of glyceroyl group cm ^-1, the absorption due to the expansion and contraction motion of the carbonyl group 1690 cm ^-1 was observed. (2) ¹³ C-NMR Measurement Method When measured at 35 ° C. using JOEL GX-400 manufactured by JEOL Ltd. using CD ₃ OD as a solvent, 207 ppm, 162 ppm, 144 ppm, 13
1 ppm, 129 ppm, 120 ppm, 116 ppm
Signal derived from the carbon of the styryl ketone moiety is 1
A signal derived from carbon in the glyceryl moiety and a signal derived from sorbitol were observed at 01 ppm to 62 ppm, respectively. (3) ¹ H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using CD ₃ OD as a solvent, δ
A signal derived from hydrogen in the styryl ketone portion was observed at 8 to 7 ppm, and a signal derived from hydrogen in the glyceryl portion and sorbitol portion was observed at δ 5.8 to 3.5 ppm. (4) Ultraviolet Absorber Spectrum Measurement Method Using a UVIDEC 610C ultraviolet absorption spectrum measurement device manufactured by JASCO Corporation, the maximum absorption was shown at 323.0 nm when measured with a solvent methanol. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown.

Example 14 6-Methoxy-3- (4,4-dimethyl-3-oxo-
1-pentenyl) phenylglycerol maltitol ether maltitol 8.07 g, sodium hydroxide 283 mg
Was dissolved in 100 ml of dimethylsulfoxide, and the mixture was heated and stirred under a nitrogen stream for 30 minutes.
-(4-methoxy-5-glycidyloxyphenyl) -ethenyl] ketone (2.1 g) was treated with dimethyl sulfoxide (20 m).
The solution dissolved in 1 was dropped. Furthermore, after heating and stirring for 1 hour under a nitrogen stream, the mixture was allowed to cool to room temperature and neutralized with hydrochloric acid. The reaction system was fractionated by column chromatography using a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.) using purified water as a developing solvent, and then using ethyl alcohol: purified water = 1: 1 as a developing solvent. The ethyl alcohol: purified water = 1: 1 eluted portion was concentrated to give 6-methoxy-
2. 3- (4,4-dimethyl-3-oxo-1-pentenyl) phenylglycerol maltitol ether
4 g were obtained. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
stretching vibration of glyceroyl group cm ^-1, the absorption due to the expansion and contraction motion of the carbonyl group 1690 cm ^-1 was observed. (2) ¹³ C-NMR Measurement Method When measured at 35 ° C. using JOEL GX-400 manufactured by JEOL Ltd. using CD ₃ OD as a solvent, 207 ppm, 162 ppm, 144 ppm, 13
1 ppm, 129 ppm, 120 ppm, 116 ppm
Signal derived from the carbon of the styryl ketone moiety is 1
A signal derived from carbon in the glyceryl moiety and a signal derived from maltitol were observed at 01 ppm to 62 ppm, respectively. (3) ¹ H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using CD ₃ OD as a solvent, δ
A signal derived from hydrogen of the styryl ketone moiety was observed at 8 to 7 ppm, and a signal derived from hydrogen of the glyceryl moiety and maltitol moiety was observed at δ 5.8 to 3.5 ppm. (4) Ultraviolet Absorber Spectrum Measurement Method Using a UVIDEC 610C ultraviolet absorption spectrum measurement device manufactured by JASCO Corporation, the maximum absorption was shown at 323.0 nm when measured with a solvent methanol. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown.

Example 15 6-Methoxy-3- (4,4-dimethyl-3-oxo-
1-pentenyl) phenylglycerol maltotriol ether maltotriol 12.1 g, sodium hydroxide 283
mg was dissolved in 60 ml of dimethyl sulfoxide, and the mixture was heated and stirred under a nitrogen stream for 30 minutes, and then t-butyl [2- (4-methoxy-5-glycidyloxyphenyl) -ethenyl] ketone 2 obtained in Example 13 was obtained. A solution of 0.1 g in 20 ml of dimethyl sulfoxide was added dropwise. Furthermore, after heating and stirring for 1 hour under a nitrogen stream, the mixture was allowed to cool to room temperature and neutralized with hydrochloric acid. First, purified water was used as the developing solvent by column chromatography of a hyperporous polymer (a high-porous resin manufactured by Mitsubishi Kasei Kogyo Co., Ltd.) as a developing solvent.
Next, fractionation was performed using ethyl alcohol: purified water = 1: 1, and the eluted portion of ethyl alcohol: purified water = 1: 1 was concentrated to give 6-methoxy-3- (4,4-dimethyl-3-oxo-). 2.1 g of 1-pentenyl) phenylglycerol maltotriol ether was obtained. (1) Infrared absorption spectrum measurement method Using an IRA-1 infrared absorption spectrum measurement apparatus manufactured by JASCO Corporation, the measurement was performed by the KBr tablet method.
Stretching movement of stretching vibration of hydroxyl group at 350 cm ^-1 , 2900
stretching vibration of glyceroyl group cm ^-1, the absorption due to the expansion and contraction motion of the carbonyl group 1690 cm ^-1 was observed. (2) ¹³ C-NMR Measurement Method When measured at 35 ° C. using JOEL GX-400 manufactured by JEOL Ltd. using CD ₃ OD as a solvent, 207 ppm, 162 ppm, 144 ppm, 13
1 ppm, 129 ppm, 120 ppm, 116 ppm
Signal derived from the carbon of the styryl ketone moiety is 1
From 01 ppm to 62 ppm, a signal derived from carbon in the glyceryl moiety and a signal derived from maltotriol were respectively observed. (3) ¹ H-NMR measurement method JOEL GX-400 manufactured by JEOL Ltd.
When measured at room temperature using CD ₃ OD as a solvent, δ
A signal derived from hydrogen in the styryl ketone portion was observed at 8 to 7 ppm, and a signal derived from hydrogen in the glyceryl portion and maltotriol portion was observed at δ 5.8 to 3.5 ppm. (4) Ultraviolet Absorber Spectrum Measurement Method Using a UVIDEC 610C ultraviolet absorption spectrum measurement device manufactured by JASCO Corporation, the maximum absorption was shown at 323.0 nm when measured with a solvent methanol. (5) Phenol indicator The product was spotted on TLC and sprayed with a phenol indicator using a nebulizer, followed by spraying with a 10% aqueous sodium hydrogen carbonate solution, but no coloration of phenol was shown. Test Example 1 Production of a serum A serum containing a styryl ketone derivative and a serum containing a 2-hydroxy-4-methoxy-5-sulfoxonium benzophenone as a control were prepared as shown in Table 1. Manufactured.

[0035]

Table 1 Ingredients Formulation Example 1 Control Example 1 ───────────────────────────── A (alcohol phase) Ethanol 5.0 5.0 POE oleyl alcohol ether 2.0 0 Appropriate amount of perfume ────────────────────────────────── B (aqueous phase) 1,3-butylene Glycol 5.0 5.0 Styryl ketone derivative (Example 1) 8.0 _ 2-human peroxy-4-methoxy-5-sulfoxonium benzoisophenone _ 8.0 triethanolamine 0.1 0.1 carboxyvinyl polymer 0.15 0.15 Purified water residue residue The alcohol phase A was added to the aqueous phase B, to obtain a beauty lotion perfume was solubilized. In Formulation Example 1, a colorless, transparent and viscous good serum was obtained, whereas in Control Example 1, yellowish color was strong and non-viscous. Test Example 2 Sunscreen test An actual use test on the beach was performed using the two serums produced in Test Example 1. As a method, samples were applied to the left and right halves respectively on the backs of 10 panelists, and the degree of sunburn was determined. The criteria were as follows. Evaluation criteria for degree of sunburn Strong erythema was observed... × Slight erythema was observed... △ Erythema was not observed ○ 結果 The results are shown in Table 2.

[0036]

[Table 2] サ ン プ ル Sample application of Comparative Example 1 of Formulation Example 1 Section Sample application section ──────────────────────────────────── Panel A ○ ○ B ○ × C △ × D △ △ E △ △ F ○ △ G ○ ○ H ○ △ I △ △ J ○ × ─────────────────────────────数 Number of skin trouble None None 2 itch 3 Itching 1 rash ─────────────────────────────よ り Based on these results, topical skin preparations containing styryl ketone derivatives have a higher UV protection effect than conventional skin preparations containing a water-soluble UV absorber, have no skin problems, and are safer. Was highly likely . Test Example 3 Humidity A change in skin conductance of 15 men and women was measured in an environment of room temperature 25 ° C. and 50% relative humidity. The serum prepared in Test Example 1 was applied to the arm, and the skin conductance of the arm was measured 24 hours after the treatment, and a judgment was made based on the increase rate. The judgment was made as follows. Conductance increase rate = Conductance value increase amount / Conductance value before treatment Humidity determination criteria Conductance increase rate less than 15% ............ Conductance increase rate 15% or more and less than 30% ...... △ Conductance increase rate 30% Above ............ The results are as shown in Table 3.

[0037]

[Table 3] Judgment Application part of Formulation Example 1 Application part of Control Example 1 ─────────────────────── ○ 256 △ 58 × 0 16 ────────────────── ──────────

From the above, it was found that a skin external preparation containing a styryl ketone derivative was superior in moisturizing property to a skin external preparation containing a conventional water-soluble ultraviolet absorber. Hereinafter, examples of the formulation of the skin external preparation according to the present invention will be described. In addition, each external preparation for skin showed an excellent ultraviolet protection effect.

Example 16 Cream A. Oil phase Stearyl acid 10.0 Stearyl alcohol 4.0 Monoglycerin stearate 8.0 Vitamin E acetate 0.5 Fragrance 0.4 Ethyl paraben 0.1 Butyl paraben 0.1 Propyl paraben 0.1 B. Aqueous phase Propylene glycol 8.0 Glycerin 2.0 4- (4,4-Dimethyl-3-oxo-1-pentenyl) phenylglycerol maltitol ether 8.0 Potassium hydroxide 0.4 Ethate trinitrile 0.05 Purification Water residue <Production method> The oil phase of A and the aqueous phase of B are each heated to 70 ° C and completely dissolved. Add phase A to phase B and emulsify with an emulsifier. The emulsion was cooled using a heat exchanger to obtain a cream.

Example 17 Cream A. Oil phase Cetanol 4.0 Vaseline 7.0 Isopropyl myristate 8.0 Squalane 12.0 Dimethylpolysiloxane 3.0 Monoglycerin stearate 2.2 POE (20) Sorbitan monostearate 0.5 Glycyrrhetinate stearate BHT 0.02 ethyl paraben 0.1 butyl paraben 0.1 propyl paraben 0.1 B. Aqueous phase 1,3-butylene glycol 7.0 Dinatrilum edetate 0.07 Phenoxyethanol 0.2 L-ascorbic acid phosphate magnesium salt 3.0 Polyacrylic acid alkyl ester 1.0 4- (4,4-dimethyl- 3-Oxo-1-pentenyl) phenyl glycerol maltotriol ether 8.0 Purified water residue <Production method> A cream was obtained according to Example 16.

Example 18 Emulsion A. Oil phase Oleyl oleate 3.0 Vaseline 7.0 Squalane 5.0 Sorbitan sesquioleate 0.8 Polyoxyethylene oleyl ether (20EO) 1.2 Glyceryl dip-methoxycinnamate 3.0 Methylparaben 0.1 Fragrance 0.12 B. Water phase Dipropylene glycol 5.0 Ethanol 3.0 Carboxyvinyl polymer 0.17 Sodium hyaluronate 0.01 Polyacrylic acid alkyl ester 1.0 4- (4,4-Dimethyl-3-oxo-1-pentenyl) phenyl Glycerol sorbitol ether 4.0 potassium hydroxide 0.08 sodium hexametaphosphate 0.05 purified water residue <Production method> An emulsion was obtained according to Example 16.

Example 19 Cream A. Oil phase Behenyl alcohol 0.5 12-Hydroxystearic acid cholestanol ester 2.0 Squalane 7.0 Jojoba oil 5.0 Self-emulsifying monosteering reserin 2.5 Polyoxyethylene sorbitan monostearate (20EO) 1.5 2 -Hydroxy-4-methoxybenzophenone 3.0 ethyl paraben 0.2 butyl paraben 0.1 propyl paraben 0.1 B. Water phase Propylene glycol 5.0 Natrilum edetate 0.08 Glycerin 5.0 Vegum (montmorillonite) 3.0 Potassium hydroxide 0.3 2-Methoxy-4- (4,4-dimethyl-3-oxo-1- (Pentenyl) phenyl glycerol maltitol ether 8.0 Purified water residue <Production method> A cream was obtained according to Example 16.

Example 20 Powdered lotion A. Oil phase Ethanol 8.0 POE (60) Glyceryl monoisostearate 2.0 L-Menthol 0.1 Camphor 0.1 Methyl paraben 0.2 Fragrance 0.03 B. Aqueous phase glycerin 3.5 2-methoxy-4- (4,4-dimethyl-3-oxo-1-pentenyl) phenylglycerol maltotriol ether 4.0 zinc 1.5 kaolin 0.5 bentonite 0.3 sodium hexametaphosphate 0.03 Purified water residue <Production method> A cream was obtained according to Example 16.

[0044]

As described above, according to the styryl ketone derivative of the present invention, excellent UV-A and UV-
B absorbability and compatibility with polar solvents. Further, the external preparation for skin containing the compound can be compounded also with a polar base and can exhibit excellent usability.

[Brief description of the drawings]

FIG. 1 is an infrared absorption spectrum chart of 4- (4,4-dimethyl-3-oxo-1-pentenyl) phenylglycerol maltitol ether according to one example of the present invention.

FIG. 2 is a ¹³ C-NMR spectrum chart of 4- (4,4-dimethyl-3-oxo-1-pentenyl) phenylglycerol maltitol ether according to one example of the present invention.

FIG. 3 is a ¹ H-NMR spectrum chart of 4- (4,4-dimethyl-3-oxo-1-pentenyl) phenylglycerol maltitol ether according to ^one example of the present invention.

FIG. 4 is an ultraviolet absorption spectrum chart of 4- (4,4-dimethyl-3-oxo-1-pentenyl) phenylglycerol maltitol ether according to one example of the present invention.

──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Sadaki Takada 1050 Nippa-cho, Kohoku-ku, Yokohama City, Kanagawa Prefecture Shiseido First Research Center Co., Ltd. (56) References JP-A-5-43585 (JP, A) JP-A-4-270298 (JP, A) JP-A-4-305592 (JP, A) JP-A-4-1344042 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07C 49/255 A61K 7/00 A61K 7/42 A61K 7/48 C09K 3/00 104 CA (STN) REGISTRY (STN)

Claims (3)

(57) [Claims] 1. A styryl ketone derivative represented by the following general formula 1. Embedded image Here, R is hydrogen or hydroxyl or alkoxyl group, A represents a sugar alcohol, G is you corresponds to 1 mole of glycerin. 2. An ultraviolet absorbent comprising the styryl ketone derivative according to claim 1. 3. An external preparation for skin, comprising one or more styryl ketone derivatives according to claim 1.