WO2014069555A1 - プロピルフェニルエーテル誘導体、並びにそれを含むメラニン生成抑制剤、美白剤、抗菌剤及び化粧料 - Google Patents
プロピルフェニルエーテル誘導体、並びにそれを含むメラニン生成抑制剤、美白剤、抗菌剤及び化粧料 Download PDFInfo
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- WO2014069555A1 WO2014069555A1 PCT/JP2013/079498 JP2013079498W WO2014069555A1 WO 2014069555 A1 WO2014069555 A1 WO 2014069555A1 JP 2013079498 W JP2013079498 W JP 2013079498W WO 2014069555 A1 WO2014069555 A1 WO 2014069555A1
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- FQVRGOADVBIZQX-UHFFFAOYSA-N CCC(C)(C)c(cc1)ccc1OC(CO)CO Chemical compound CCC(C)(C)c(cc1)ccc1OC(CO)CO FQVRGOADVBIZQX-UHFFFAOYSA-N 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
- A01N31/08—Oxygen or sulfur directly attached to an aromatic ring system
- A01N31/14—Ethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/39—Derivatives containing from 2 to 10 oxyalkylene groups
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/12—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group, wherein Cn means a carbon skeleton not containing a ring; Thio analogues thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/345—Alcohols containing more than one hydroxy group
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
- A61K8/375—Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/257—Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings
- C07C43/295—Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings containing hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/21—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/22—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety
- C07C69/28—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety esterified with dihydroxylic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/22—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety
- C07C69/30—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety esterified with trihydroxylic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/005—Antimicrobial preparations
Definitions
- the present invention relates to a propylphenyl ether derivative suitably used as a raw material for cosmetics.
- the present invention also relates to a cosmetic comprising the propylphenyl ether derivative as an active ingredient, a melanin production inhibitor, a whitening agent, an antibacterial agent, and the propylphenyl ether derivative.
- cosmetics are often used in anticipation of various effects such as whitening effects such as melanin production suppression effects and antibacterial effects, and anti-acne, anti-dandruff and anti-wrinkle effects. Then, what has the said effect is desired for the raw material of cosmetics. Especially, the expectation for the whitening effect, especially the melanin production inhibitory effect is great.
- kojic acid, arbutin, vitamin C, and derivatives thereof have an effect of suppressing the formation of melanin and preventing blackening, but the effect is insufficient. Furthermore, many of kojic acid, vitamin C, and derivatives thereof have a problem of coloring over time when blended in cosmetics.
- Patent Document 1 proposes hydroquinone alkyl ethers and the like, but these have hydroquinone as a mother skeleton, and there is concern about safety.
- acylated derivatives of 2- (4-hydroxyphenyl) ethanol having a phenolic hydroxyl group Patent Document 2
- alkylphenyl ether glycosides Patent Document 3
- these derivatives are generally considered to have poor stability because the phenolic hydroxyl group is bonded by an ester bond or glycoside bond, and the phenolic hydroxyl group is liberated by hydrolysis, leading to safety. Is concerned about the problem.
- Alkylphenols such as tert-butylphenol are also known as compounds having a high melanin production inhibitory effect. However, these compounds have low safety and cannot be applied to cosmetics (Non-patent Document 1).
- JP-A-6-192062 Japanese Patent No. 4658898 Japanese Patent No. 3340930 Japanese Patent No. 4828126
- this invention makes it a subject to provide the compound suitably used as a raw material of cosmetics which has the outstanding melanin production inhibitory effect (whitening effect) and the antibacterial effect, and is excellent also in temporal stability.
- Another object of the present invention is to provide a melanin inhibitor and a whitening agent that contain the compound as an active ingredient, prevent skin darkening, and improve pigmentation such as spots and freckles.
- Another object of the present invention is to provide an antibacterial agent containing the compound as an active ingredient and capable of preventing bacterial contamination, acne and dandruff in cosmetics.
- Another object of the present invention is to provide a cosmetic, particularly a whitening cosmetic, characterized by blending the above compound.
- the present invention provides a propylphenyl ether derivative represented by the following general formula (I), (Ia) or (Ib) (Claim 1).
- R represents —CH 2 —CHR 2 —CH 2 R 1 or —CH (CH 2 R 2 ) —CH 2 R 1
- Ra represents —CH 2 —CHR 2 —CH 2 —O—CH 2 —CHR 2 —CH 2 — or —CH 2 —CHOH—CH 2 —
- Rb represents a linear or branched aliphatic hydrocarbon group having 1 to 5 carbon atoms
- R 1 and R 2 are each independently hydrogen, R 8 O, R 9 S, R 10 R 11 N, R 12 A, straight or branched, saturated or unsaturated, having 1 to 22 carbon atoms
- R 8 , R 9 , R 10 , R 11 and R 12 are each independently a linear or branched, saturated or unsaturated aliphatic hydrocarbon group having 1 to 22 carbon atoms
- R 1 and R 2 are simultaneously a group selected from the group consisting of a hydroxyl group and a group represented by R 12 A—, and A is a phosphate ester group, a sulfate ester group, an ester group or a salt thereof,
- the total number of carbon atoms of R 3 , R 4 , R 5 , R 6 and R 7 is 2 or more.
- a propylphenyl ether derivative compound of formula (I) are represented by the following structural formula (Ic) or structural formula (Id), respectively.
- R 1 and R 2 and R 8 , R 9 , R 10 , R 11 and R 12 may be an aliphatic hydrocarbon having 1 to 22 carbon atoms or a cyclic hydrocarbon having 3 to 22 carbon atoms.
- the aliphatic hydrocarbon having 1 to 22 carbon atoms may be either linear or branched, and in any case of linear or branched, any saturated or unsaturated carbon It may be hydrogen.
- the C3-C22 cyclic hydrocarbon means a hydrocarbon having a saturated or unsaturated ring, and the unsaturated ring includes an aromatic ring.
- the hydrogen may be substituted with a hydroxyl group.
- R 3 , R 4 , R 5 , R 6 and R 7 may be an aliphatic hydrocarbon having 1 to 12 carbon atoms.
- the aliphatic hydrocarbon having 1 to 12 carbon atoms may be linear or branched, and in any case of linear or branched, a saturated hydrocarbon. Or an unsaturated hydrocarbon.
- R 1 or R 2 may be a functional group represented by R 12 A.
- the phosphate group, sulfate group, ester group, thioester group and amide group represented by A are:
- Each is a divalent group represented by the structural formula shown below.
- * represents a bonding group to R 12 .
- R 1 or / and R 2 are hydrogen and have 1 to 22 carbon atoms.
- a propylphenyl ether derivative which is a group selected from a linear or branched, saturated or unsaturated aliphatic hydrocarbon group, R 8 O, R 9 S and R 10 R 11 N is capable of producing more excellent melanin. It is preferable because it shows a suppressing effect. Especially, it is more preferable when R 1 is R 8 O and R 2 is a hydroxyl group.
- the present invention is represented by the general formula (I), (Ia) or (Ib), and R 1 or / and R 2 are hydrogen, linear or branched having 1 to 22 carbon atoms.
- a propylphenyl ether derivative in which R 2 is a hydroxyl group (Claim 3).
- the present invention is preferably a propylphenyl ether derivative wherein R 1 is R 8 O and R 2 is a hydroxyl group, and the propylphenyl ether derivative represented by the general formula (I) (claim) Item 4) is provided.
- R 8 is hydrogen or a linear or branched, saturated or unsaturated aliphatic hydrocarbon group having 1 to 22 carbon atoms (Claim 5) are particularly preferable.
- R 8 is preferably a linear or branched, saturated or unsaturated aliphatic hydrocarbon group having 1 to 22 carbon atoms (claim 6).
- R 2 is represented by R 12 A and A is a phosphate ester group, a sulfate ester group, an ester group or a salt thereof are easily hydrolyzed by phosphatase, esterase, etc. in vivo. And a propylphenyl ether derivative exhibiting a particularly excellent melanin production inhibitory effect.
- R 2 is preferably represented by R 12 A, and A is a phosphate ester group, a sulfate ester group, an ester group, or a salt thereof, since it exhibits an excellent melanin production inhibitory effect.
- R 3 , R 4 , R 5 , R 6 and R 7 are hydrogen or linear or branched having 1 to 12 carbon atoms. Those which are in the form of saturated or unsaturated aliphatic hydrocarbons are preferred because they exhibit an excellent melanin production inhibitory effect. Among them, at least one group of R 3 , R 4 , R 5 , R 6 and R 7 is a branched aliphatic hydrocarbon, and the carbon number of R 3 , R 4 , R 5 , R 6 and R 7 A total of 4 or more is more preferable. More preferably, at least one group of R 3 , R 4 , R 5 , R 6 and R 7 is a tert-butyl group or a sec-butyl group.
- propylphenyl ether derivative compounds represented by the general formula (Ia) and the propylphenyl ether derivatives that are salts thereof those in which Ra is —CH 2 —CH (OH) —CH 2 — have excellent melanin production inhibition. This is preferable because it shows an effect. Therefore, as a preferred embodiment of the present invention, a propylphenyl ether derivative represented by the general formula (Ia), wherein Ra is —CH 2 —CH (OH) —CH 2 — (claims) 10).
- the present invention provides, as a preferred embodiment thereof, a propylphenyl ether derivative represented by the general formula (Ib), wherein Rb is —C (CH 3 ) 2 — (claim 11). To do.
- a carbon atom and a hydrogen atom bonded to the carbon atom may be omitted.
- the 1st and 3rd positions (of the propyl group) are CH 2 groups, and the 2nd position is a CH group.
- the positions of the 1′-position and 4′-position (of the phenyl group) are carbon atoms, and the positions of the 2′-position, 3′-position, 5′-position and 6′-position are CH groups.
- the group bonded to the 4 ′ position is a tert-butyl group, and the group bonded to the 1 position is an ethoxy group.
- a propylphenyl ether derivative represented by the structural formula (II) (Claim 12).
- a propylphenyl ether derivative represented by the structural formula (A) (claim 13).
- a propylphenyl ether derivative represented by the structural formula (C) (Claim 14).
- a propylphenyl ether derivative represented by the structural formula (E) (claim 15).
- a propylphenyl ether derivative represented by the structural formula (F) (claim 16).
- a propylphenyl ether derivative represented by the structural formula (G) (claim 17).
- a propylphenyl ether derivative represented by the structural formula (H) (claim 18).
- a propylphenyl ether derivative represented by the structural formula (P) (claim 19).
- a propylphenyl ether derivative represented by the structural formula (J) (claim 20).
- a propylphenyl ether derivative represented by the structural formula (K) (claim 21).
- the propylphenyl ether derivative of the present invention represented by the general formula (I) exhibits an excellent melanin production inhibitory effect, an excellent whitening effect, an excellent antibacterial effect, and has an excellent stability. (Including an external preparation for skin) can be suitably blended. Therefore, the present invention provides the following melanin production inhibitor, whitening agent, antibacterial agent, and cosmetics in addition to the propylphenyl ether derivative.
- the present invention provides a melanin production inhibitor comprising the propylphenyl ether derivative according to any one of claims 1 to 21 as an active ingredient (claim 22).
- the propylphenyl ether derivative represented by the formula (III) or the formula (D) exhibits an excellent melanin production inhibitory effect.
- a melanin production inhibitor (Claim 23) which comprises a propylphenyl ether derivative represented by the formula (III) as an active ingredient (Claim 23),
- Formula (D) A melanin production inhibitor (claim 24), characterized in that a propylphenyl ether derivative represented by formula (1) is blended as an active ingredient.
- the present invention also provides a whitening agent comprising the propylphenyl ether derivative according to any one of claims 1 to 21 as an active ingredient (claim 25).
- the present invention further provides an antibacterial agent comprising the propylphenyl ether derivative according to any one of claims 1 to 21 as an active ingredient (claim 26).
- the present invention provides a cosmetic comprising the propylphenyl ether derivative compound according to any one of claims 1 to 21 and a salt thereof (claim 27).
- the blending amount of the propylphenyl ether derivative of the present invention in cosmetics is usually preferably 0.0001 mass% to 10 mass%. When the amount is less than 0.001% by mass, the melanin production inhibitory effect and antibacterial effect of the present invention are often not sufficiently exhibited. On the other hand, when it exceeds 10 mass%, there is a possibility that the agent system may be broken, and an effect commensurate with the blending amount is often not expected.
- the cosmetic of the present invention is preferably used as a whitening cosmetic for the purpose of whitening. It can also be suitably used as a cosmetic for antibacterial purposes.
- the propylphenyl ether derivative compound or a salt thereof represented by the general formula (I) of the present invention has an excellent melanin production inhibitory effect and antibacterial effect, and is excellent in stability. Therefore, the melanin production inhibitor of the present invention, characterized by blending this propylphenyl ether derivative as an active ingredient, exhibits excellent melanin production inhibitory effect and whitening effect and is excellent in stability and used as a whitening agent. It is done.
- the antibacterial agent of the present invention which contains this propylphenyl ether derivative as an active ingredient, has an excellent antibacterial effect.
- the cosmetic of the present invention is suitably used as a cosmetic having an excellent whitening effect.
- propylphenyl ether derivative compound of the present invention include the following compounds.
- 1-O-alkyl-2-hydroxy-3- (4′-alkylphenoxy) propyl 1-O-alkyl-2-hydroxy-3- (2′-alkylphenoxy) propyl, 1-O-alkyl-2-hydroxy-3- (3′-alkylphenoxy) propyl, 1-alkyl-2-hydroxy-3- (4′-alkylphenoxy) propyl, 1-alkyl-2-hydroxy-3- (2′-alkylphenoxy) propyl, 1-alkyl-2-hydroxy-3- (3′-alkylphenoxy) propyl, 1,2-di-hydroxy-3- (4′-alkylphenoxy) propyl, 1,2-di-hydroxy-3- (2′-alkylphenoxy) propyl, 1,2-di-hydroxy-3- (3′-alkylphenoxy) propyl, 1,3-di-hydroxy-2- (4′-alkylphenoxy) propyl, 1,3-di-hydroxy-2- (4′
- O-alkyl means an alkoxy group
- N-alkyl means an alkylamino group or a diaminoalkyl group
- S-alkyl means a thioalkoxy group
- alkyl in the above exemplary compounds examples include methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group.
- Linear alkyl groups such as pentadecyl group, hexadecyl group, heptadecyl group, octadecyl group, nonadecyl group, behenyl group, Isopropyl group, isobutyl group, sec-butyl group, tert-butyl group, isopentyl group, neopentyl group, sec-pentyl group, tert-pentyl group, isohexyl group, neohexyl group, sec-hexyl group, tert-hexyl group, 2- Methylpentyl group, 3-methylpentyl group, 2,2-dimethylbutyl group, 2-ethylbutyl group, isoheptyl group, isooctyl group, neooctyl group, sec-octyl group, tert-octyl group, isonon
- alkyl in the above exemplary compound is an alkenyl group such as vinyl group, allyl group, butenyl group, isobutenyl group, crotyl group, octenyl group, decenyl group, dodecenyl group, etc.
- a replacement can also be mentioned.
- acyl in the above exemplary compounds acetyl group, formyl group, propanoyl group, butanoyl group, pentanoyl group, hexanoyl group, heptanoyl group, octanoyl group, nonyl group, decanoyl group, undecanoyl group, dodecanoyl group, tetradecanoyl group, Hexadecanoyl group, octadecanoyl group, eicosanoyl group, hexadecenoyl group, octadecenoyl group, oleyl group, octadecatrienoyl group, icosatetraenoyl group, isooctanoyl group, isopalmitoyl group, isostearoyl group, 2-propylpentanoyl group Group, 2-butylhexanoyl group, 2-pentyl group
- a compound in which the phosphoryl group in the above exemplary compounds is replaced with an alkyl phosphoryl group is also included in the present invention.
- the propylphenyl ether derivative of the present invention can be produced by various known methods. For example, a method of reacting a phenol compound represented by the following structural formula (IV) with an alkyl halide represented by the following structural formula (V) can be mentioned.
- R 3 , R 4 , R 5 , R 6 and R 7 represent the same meaning as in the general formula (I), and X represents halogen.
- a method of reacting a phenol compound represented by the structural formula (IV) with an epoxy compound such as glycidol, glycidyl ether, or epoxy alkane, a phenol compound represented by the structural formula (IV), an alkyl halide, or a dialkyl sulfate can also be mentioned.
- an acylated product can be obtained by reacting the propylphenyl ether derivative obtained by the above method with an acylating agent such as an acid anhydride or an acid halide.
- the type of solvent that can be used in the above reaction is not particularly limited.
- the solvent may be a solvent selected from water, lower alcohols such as methanol, ethanol, isopropanol, dimethyl sulfoxide (DMSO), N, N-dimethylformamide (DMF), dioxane, tetrahydrofuran (THF), pyridine, etc.
- a mixed solvent can be mentioned.
- the water-containing solvent include those composed only of water and a mixed solvent of a solvent mainly composed of water and selected from lower alcohols such as methanol, ethanol and isopropanol, DMSO, DMF, dioxane, THF, pyridine and the like.
- the target product can be obtained without using a solvent, it is not necessary to use a solvent.
- the above reaction can also be performed using a catalyst such as an acid catalyst, a basic catalyst, or a phase transfer catalyst.
- a catalyst such as an acid catalyst, a basic catalyst, or a phase transfer catalyst.
- the propylphenyl ether derivative produced as described above is purified by means such as column chromatography using silica gel, column chromatography using a resin such as an ion exchange resin, activated carbon treatment, extraction, distillation, crystallization and the like. be able to.
- the cosmetics of the present invention usually include components such as oily raw materials, surfactants, other moisturizers, polymer compounds, antioxidants, other whitening agents, and UV absorption.
- An agent, a sequestering agent, a protein hydrolyzate, an amino acid or a derivative thereof, a pH adjuster, a preservative, a thickener, a pigment, other drugs, and the like can be appropriately blended.
- oily raw materials include olive oil, coconut oil, macadamia nut oil, tea seed oil, castor oil, oils such as tri (caprin / capry) glyceryl, jojoba oil, carnauba wax, candelilla wax, lanolin, beeswax and other waxes, Hydrocarbons such as liquid paraffin, paraffin, petrolatum, ceresin, microcrystalline wax, squalane, fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, isostearic acid, cetyl alcohol, stearyl alcohol, isostearyl Higher alcohols such as alcohol, isopropyl myristate, 2-octyldodecyl myristate, cetyl 2-ethylhexanoate, diisostearyl malate, tri-2-ethylhexanoin, and the like, methylpolysiro Sun, methylphenyl poly
- surfactants include anionic surfactants such as higher fatty acid soaps, polyoxyethylene alkyl ether sulfates, acyl-N-methyl taurate salts, N-acyl amino acid salts, alkyl phosphate ester salts, and alkyltrimethyl chlorides.
- Cationic surfactants such as ammonium and dialkyldimethylammonium chloride, amphoteric surfactants such as alkyldimethylaminoacetic acid betaine, alkylamidoaminoacetic acid betaine, 2-alkyl-N-carboxy-N-hydroxyimidazolinium betaine, polyoxy Nonionic surfactants such as ethylene alkyl ether, polyethylene glycol fatty acid ester, polyhydric alcohol fatty acid ester, and polyether-modified silicone are listed.
- humectant examples include glycerin, propylene glycol, maltitol, sorbitol, 1,3-butylene glycol, sodium lactate, polyethylene glycol, sodium pyrrolidonecarboxylate, sodium hyaluronate, and the like.
- Examples of the polymer compound include carboxyvinyl polymer, sodium carboxymethylcellulose, xanthan gum, polyvinyl alcohol, and polymer dimethylpolysiloxane.
- Examples of the antioxidant include vitamin E, tannin, BHT (butylhydroxytoluene) and the like.
- the propylphenyl ether derivative of the present invention has a whitening effect, but other whitening agents can be added to the cosmetic of the present invention.
- other whitening agents include ellagic acid, kojic acid, chamomile extract, licorice extract, lucinol, rosemary extract, arbutin, tranexamic acid, 4-methoxysalicylic acid potassium salt, ascorbic acid, glyceryl ascorbic acid, ascorbic acid glucoside, Examples include ascorbic acid derivatives such as magnesium ascorbate phosphate.
- ultraviolet absorber examples include ethyl hexyl methoxycinnamate, octocrylene, 4-tert-butyl 4'-methoxydibenzoylmethane, hexyl diethylaminohydroxybenzoyl benzoate and the like.
- sequestering agent examples include citramalic acid, agaric acid, glyceric acid, shikimic acid, hinokitiol, gallic acid, tannic acid, caffeic acid, ethylenediaminetetraacetic acid, ethylene glycoldiaminetetraacetic acid, diethylenetriaminepentaacetic acid, phytic acid, polyphosphoric acid Examples thereof include acids, metaphosphoric acids, analogs thereof, and alkali metal salts and carboxylic acid esters thereof.
- protein hydrolysates include protein hydrolysates such as milk protein, silk protein, wheat protein, rice protein, pea protein, collagen, keratin, soybean, sesame, conchiolin, marine collagen, and derivatives thereof.
- amino acids or derivatives thereof include glycine, valine, leucine, isoleucine, serine, threonine, phenylalanine, arginine, lysine, asparagine, aspartic acid, glutamine, glutamic acid, cystine, cysteine, methionine, tryptophan, proline, histidine and the like. Examples include amino acids and their derivatives.
- Examples of the pH adjuster include lactic acid, citric acid, glycolic acid, succinic acid, tartaric acid, malic acid, potassium carbonate, sodium hydrogen carbonate, ammonium hydrogen carbonate and the like.
- Examples of the preservative include paraoxybenzoic acid alkyl ester, benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, and phenoxyethanol.
- thickeners examples include gum arabic, gum tragacanth, cablo gum, guar gum, pectin, agar, quince seed, starch, alge colloid, xanthan gum, dextran, succinoglucan, collagen, gelatin, casein, albumin, carboxymethyl starch, methylcellulose , Ethyl cellulose, methyl hydroxypropyl cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, nitrocellulose, sodium cellulose sulfate, sodium carboxymethyl cellulose, sodium arginate, polyvinyl methyl ether, carboxyvinyl polymer, sodium polyacrylate, polyethylene acrylate, poly Acrylamide, cationic polymer, etc. And the like.
- pigments include tar pigments, natural pigments, inorganic pigments, and polymer powders.
- fragrances include natural fragrances, synthetic fragrances, and blended fragrances.
- rough skin prevention agents or anti-inflammatory agents can be mentioned.
- the rough skin preventive agent or anti-inflammatory agent include dipotassium glycyrrhizinate, stearyl glycyrrhetinate, methyl salicylate, pyridoxine hydrochloride, allantoin, sea salt, scotch extract, aloe extract, gardenia extract, chamomile extract, licorice extract, mukuroji extract, Kyounin extract, Ogon extract, strawberry tea extract, loquat extract, ginkgo biloba extract, hypericum extract, sorghum extract, safflower extract, spruce extract, salvia extract, birch extract, chimpi extract, tonin extract, gayo extract,retea extract, arnica extract, carrot extract, peony extract , Cucumber extract, gentian extract, cordyceps extract, duckweed extract, ginseng extract, ginseng extract, peach leaf Kiss, kumazasa extract
- the cosmetic agent system of the present invention is arbitrary, and any of a solution system, a solubilization system, an emulsification system, a gel system, a powder dispersion system, a water-oil two-layer system, and the like can be used. It can be produced by blending the hydroxypropylalkylphenyl ether derivative represented by the above general formula (I) or a salt thereof and the above optional blending component.
- Synthesis Example 1 Synthesis of 1- (4′-tert-butylphenoxy) propyl Sodium hydroxide (0.26 g) and tetrabutylammonium bromide (0.43 g) were added to 4-tert-butylphenol (1.00 g) at room temperature. , And propyl bromide (1.64 g) was added. After further stirring at 50 ° C. for 5 hours, ethyl acetate and water were added, and the desired product was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and 1.37 g of the resulting residue was subjected to silica gel column chromatography.
- Synthesis Example 4 Synthesis of 1,2-di-hydroxy-3- (2′-methylphenoxy) propyl 2-methylphenol (1.00 g), sodium hydroxide (0.37 g), tetrabutylammonium bromide (0. 30 g) and the mixture was stirred at room temperature, glycidol (0.75 g) was added, and the mixture was further stirred at 50 ° C. for 5 hours, followed by extraction with ethyl acetate and water. The extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and 1.49 g of the resulting residue was subjected to silica gel column chromatography.
- the obtained product was subjected to 1 H-NMR and 13 C-NMR measurements, and from this measurement result, this product was obtained as 1,2-di-hydroxy-3- (1) represented by the structural formula (III). 4′-tert-butylphenoxy) propyl was confirmed.
- the product L was subjected to 1 H-NMR and 13 C-NMR measurements, and based on the measurement results, the product L was represented by 1-O-ethyl-2-hydroxy-3- represented by the structural formula (II). It was confirmed to be (4′-tert-butylphenoxy) propyl.
- the product M was also subjected to 1 H-NMR and 13 C-NMR measurements. From the measurement results, the product M was 2-O-ethyl-1-hydroxy-3- represented by the following structural formula (VI). It was confirmed to be (4′-tert-butylphenoxy) propyl.
- the product A was subjected to 1 H-NMR and 13 C-NMR measurements. From the measurement results, the product A was obtained as 1-O-ethyl-2-hydroxy-3- represented by the structural formula (A). It was confirmed to be (4′-sec-butylphenoxy) propyl.
- the product B is a compound having UV absorption by HPTLC analysis.
- the product B obtained from the raw materials and the reactivity thereof is composed of 1-hydroxy-2-O-ethyl-3- (4′-sec-butylphenoxy) propyl represented by the following structural formula (B): Conceivable.
- the obtained product was subjected to 1 H-NMR and 13 C-NMR measurements, and from this measurement result, this product was obtained as 1,2-di-hydroxy-3- represented by the structural formula (D). It was confirmed to be (4′-sec-butylphenoxy) propyl.
- Example 7 Synthesis of 1,2-di-octanoyl-3- (4′-tert-butylphenoxy) propyl 1,2-di-hydroxy-3- (4′-tert-butyl) obtained in Example 1
- phenoxy) propyl (1.00 g)
- 7 mL of DMF and triethylamine (0.30 g) were added and stirred at room temperature, and n-caprylic anhydride (0.80 g) was added. After stirring at 80 ° C. for 2 hours, ethyl acetate and water were added, and the desired product was extracted with ethyl acetate.
- Tetrabutylammonium bromide (0.19 g) and sodium hydroxide (0.24 g) were added to 1.87 g of the resulting residue, and 4-tert- Butylphenol (1.96 g) was added.
- Tetrabutylammonium bromide (0.19 g) and sodium hydroxide (0.24 g) were added to 1.87 g of the residue obtained by drying the extract over anhydrous sodium sulfate and concentrating under reduced pressure.
- the obtained 1,2-di-hydroxy-3- (4′-tert-butylphenoxy) propyl (2.19 g) was added and stirred at 80 ° C. for 2 hours, followed by extraction with ethyl acetate and water.
- the obtained product was subjected to 1 H-NMR and 13 C-NMR measurements. From the measurement results, this product was obtained as 1-O-cetyl-2-hydroxy-3- ( 4′-tert-butylphenoxy) propyl was confirmed.
- Example 17 Synthesis of 1,2-di-hydroxy-3- [4 ′-(1 ′′, 1 ′′, 3 ′′, 3 ′′ -tetramethylbutylphenoxy] propyl 4- (1,1,3,3-tetra Methylbutyl) phenol (1.00 g), sodium hydroxide (0.19 g) and tetrabutylammonium bromide (0.15 g) were added and stirred at room temperature, glycidol (0.40 g) was added, and the mixture was further heated to 50 ° C.
- the obtained product was confirmed to be a UV-absorbing compound by HPTLC analysis, and was considered to be 1-hydroxy-3- (4′-tert-butylphenoxy) propyl represented by the following structural formula from the raw material. It is done.
- Example 19 Synthesis of 1,2-di-hydroxy-3- (2 ′, 6′-di-sec-butylphenoxy) propyl 2,6-di-sec-butylphenol (1.00 g) was mixed with sodium hydroxide ( 0.19 g) and tetrabutylammonium bromide (0.16 g) were added and stirred at room temperature, and glycidol (0.40 g) was added. After further stirring at 50 ° C. for 5 hours, ethyl acetate and water were added, and the desired product was extracted with ethyl acetate.
- the obtained product was confirmed to be a UV-absorbing compound by HPTLC analysis, and 1,2-di-hydroxy-3- (2 ′, 6′-di-ester represented by the following structural formula from the raw material. -Sec-Butylphenoxy) propyl.
- Example 21 Synthesis of 1,2-di-hydroxy-3- (2 ′, 4′-di-tert-butyl-5′-methylphenoxy) propyl 2,4-di-tert-butyl-5-methylphenol ( 1.00 g), sodium hydroxide (0.18 g) and tetrabutylammonium bromide (0.15 g) were added and stirred at room temperature, glycidol (0.34 g) was added, and the mixture was further stirred at 50 ° C. for 5 hours. Then, ethyl acetate and water were added, and the target product was extracted with ethyl acetate.
- Example 22 Synthesis of 1,2-di-hydroxy-3- (2 ′, 6′-di-tert-butyl-4′-methylphenoxy) propyl 2,6-di-tert-butyl-4-methylphenol ( 1.00 g), sodium hydroxide (0.18 g) and tetrabutylammonium bromide (0.15 g) were added and stirred at room temperature, glycidol (0.34 g) was added, and the mixture was further stirred at 50 ° C. for 5 hours. Then, ethyl acetate and water were added, and the target product was extracted with ethyl acetate.
- the obtained product was confirmed to be a UV-absorbing compound by HPTLC analysis, and 1,2-di-hydroxy-3- (2 ′, 6′-di-ester represented by the following structural formula from the raw material. -Tert-Butyl-4'-methylphenoxy) propyl.
- the obtained product was confirmed to be a UV-absorbing compound by HPTLC analysis, and 1,2-di-hydroxy-3- (2′-tert-butyl-) represented by the following structural formula from the raw material. 4'-methoxyphenoxy) propyl.
- the obtained product was confirmed to be a UV-absorbing compound by HPTLC analysis, and 1,2-di-hydroxy-3- (3′-tert-butyl-) represented by the following structural formula from the raw material 4'-methoxyphenoxy) propyl.
- the obtained product was confirmed to be a UV-absorbing compound by HPTLC analysis, and 2,2-bis [4 ′-(1 ′′, 2 ′′ -di--) represented by the following structural formula from the raw material. Hydroxypropoxy) phenyl] propane.
- Example 26 Synthesis of 1-O- (2 ′′ -ethylhexyl) -2-hydroxy-3- (2′-sec-butylphenoxy) propyl 2-ethylhexyl glycidyl ether (1.00 g) was added to sodium hydroxide (0. 22 g), tetrabutylammonium bromide (0.17 g) was added and stirred at room temperature, 2-sec-butylphenol (0.89 g) was added, and the mixture was further stirred at room temperature for 5 hours.
- the obtained product was confirmed to be a UV-absorbing compound by HPTLC analysis, and 1-O- (2 ′′ -ethylhexyl) -2-hydroxy-3- ( 2′-sec-butylphenoxy) propyl.
- Example 27 Synthesis of 1-O-ethyl-2-hydroxy-3- (2′-sec-butylphenoxy) propyl 2-sec-butylphenol (1.00 g) was mixed with sodium hydroxide (0.27 g), tetrabutyl Ammonium bromide (0.22 g) was added and stirred at room temperature, ethyl glycidyl ether (0.75 g) was added, and the mixture was further stirred at 50 ° C. for 5 hours. Then, ethyl acetate and water were added, and the target product was extracted with ethyl acetate. did.
- the obtained product was subjected to 1 H-NMR and 13 C-NMR measurements. From the measurement results, this product was obtained as 1-O-ethyl-2-hydroxy-3- ( 4′- ⁇ -cumylphenoxy) propyl.
- Example 29 Synthesis of 1-O-ethyl-2-hydroxy-3- (3′-methyl-4′-isopropylphenoxy) propyl 3-Methyl-4-isopropylphenol (1.00 g) was added to sodium hydroxide (0 .27 g) and tetrabutylammonium bromide (0.22 g) were added and stirred at room temperature, ethyl glycidyl ether (0.75 g) was added, and the mixture was further stirred at 50 ° C. for 5 hours, and then ethyl acetate and water were added. The target product was extracted with ethyl.
- Example 30 Synthesis of 1-O-ethyl-2-hydroxy-3- (2 ′, 6′-di-sec-butylphenoxy) propyl Hydroxylate to 2,6-di-sec-butylphenol (1.00 g) Sodium (0.19 g) and tetrabutylammonium bromide (0.16 g) were added and stirred at room temperature. Ethyl glycidyl ether (0.54 g) was added and stirred at 50 ° C. for 5 hours, and then ethyl acetate and water were added. The target product was extracted with ethyl acetate.
- Example 31 Synthesis of 1,2-di-hydroxy-3- (3′-methyl-4′-isopropylphenoxy) propyl 3-Methyl-4-isopropylphenol (1.00 g) was mixed with sodium hydroxide (0.27 g). ), Tetrabutylammonium bromide (0.22 g) was added, and the mixture was stirred at room temperature, glycidol (0.75 g) was added, and the mixture was stirred at 50 ° C. for 5 hours. Then, ethyl acetate and water were added to extract the target product with ethyl acetate. did.
- Example 33 Synthesis of 1-O-ethyl-2-hydroxy-3- [4 ′-(1 ′′, 1 ′′, 3 ′′, 3 ′′ -tetramethylbutylphenoxy] propyl 4- (1,1,3,3 -To tetramethylbutyl) phenol (1.00 g), sodium hydroxide (0.19 g) and tetrabutylammonium bromide (0.15 g) were added and stirred at room temperature, and ethyl glycidyl ether (0.55 g) was added.
- Test Example 1 Melanin Production Inhibition Test According to the following procedure, the effect of B16 melanoma 4A5 cells on theophylline-induced melanin production was evaluated using the propylphenyl ether derivative of the present invention, the compounds obtained in Synthesis Examples 1 to 4 and arbutin. The comparison product was used. The results are shown in Tables 1 to 3.
- B16 mouse melanoma 4A5 strain was seeded in a 48-well plate at a cell density of 8.0 ⁇ 10 3 cells / well.
- D-MEM Dulbecco's modified Eagle medium
- 10% fetal bovine serum manufactured by Nichirei Biosciences
- the sample adjusted so that the final concentration was a predetermined concentration were added.
- the medium was removed using an aspirator, distilled water was added, and the cells were disrupted by ultrasound.
- the amount of protein was quantified using BCA protein assay kit (manufactured by Thermo Fisher Scientific), and the amount of melanin produced was measured by the alkali solubilization method described below.
- Alkali solubilization method Sodium hydroxide was added to the cell lysate to a final concentration of 1 mol / L and dissolved by heating (60 ° C., 30 minutes), and then the absorbance at 405 nm was measured using a microplate reader.
- the amount of melanin was calculated from a calibration curve prepared using synthetic melanin (SIGMA) as a standard product.
- the amount of melanin per unit protein was calculated by dividing the amount of melanin by the amount of protein.
- the melanin production inhibition rate was calculated from the following equation.
- Melanin production inhibition rate (%) [1 ⁇ (AB) / (CB)] ⁇ 100 [In the formula, A is the amount of melanin per unit protein at the time of sample addition (g / g), B is the amount of melanin per unit protein in the Normal group (g / g), and C is the amount per unit protein in the Control group. The amount of melanin (g / g) is shown. ]
- the Normal group is the case of theophylline (-; no addition) and the sample (-; no addition)
- the Control group is the case of theophylline (+; addition) and the sample (-; no addition).
- Tables 1 to 3 show that the hydroxypropylalkylphenyl ether derivative of the present invention has a whitening effect superior to known melanin production inhibitors, ie, kojic acid, arbutin, and ascorbic acid.
- many compounds in the hydroxypropylalkylphenyl ether derivatives of the present invention showed an effect equivalent to or better than hydroquinone, which is known as a substance having a high whitening effect, but whose safety is a concern.
- Test Example 2 Antibacterial test Using four types of bacteria (using ATCC strain) of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans The antimicrobial test was evaluated for the propylphenyl ether derivative of the present invention by the following procedure. As a comparative product, 1,2-pentanediol was used.
- the results are classified in the following criteria and shown in Table 4.
- the number of specimens in which bacteria were confirmed was 10 or more: ⁇
- the number of specimens with confirmed bacteria was 6-9: ⁇
- the number of specimens with confirmed bacteria was 5 or less:
- Test Example 4 [Stability test] Using 1,2-di-hydroxy-3- (4′-tert-butylphenoxy) propyl of Example 1, the color stability when stored at 50 ° C. for 4 weeks was evaluated in the following manner.
- As a comparative product ascorbic acid, kojic acid, hydroquinone, and arbutin, which are known whitening agents, were used.
- test sample is added to a 50% ethanol solution to a concentration of 1%, adjusted to pH 6.0 to 8.0 with dilute sodium hydroxide aqueous solution or dilute hydrochloric acid aqueous solution, respectively, put in a 50 mL screw tube and sealed tightly. And stored at 50 ° C. for 4 weeks. Immediately after preparation of the test sample, the coloration degree of the solution after 2 weeks and 4 weeks of storage was evaluated by 10 panelists based on the following criteria.
- surface after Table 9 represents a mass part.
- Example 35 Emulsion No. of the composition shown in Table 10. 1 to 10 oil phase raw materials, and 11 to 13 water phase raw materials were each heated to 70 ° C. and dissolved to prepare an oil phase and an aqueous phase, respectively. Thereafter, an oil phase was added to the aqueous phase, preliminarily emulsified and uniformly emulsified with a homomixer, and then cooled to room temperature with good stirring, thereby preparing an emulsion considered to have an excellent whitening effect.
- Example 36 Emulsion No. of the composition shown in Table 11. 4 to 10 oil phase raw materials, and The raw materials of the water phase parts 1 to 3 and 11 to 12 were each heated to 70 ° C. and dissolved to prepare an oil phase and an aqueous phase, respectively. Thereafter, an oil phase was added to the aqueous phase, preliminarily emulsified, uniformly emulsified with a homomixer, and then cooled to room temperature with good stirring, whereby an emulsion considered to have an excellent whitening effect could be prepared.
- Example 37 Cream No. 1 of the composition shown in Table 12 1 to 3 oil phase raw materials, and 4 to 10 water phase raw materials were heated to 70 ° C and dissolved to prepare an oil phase and an aqueous phase, respectively, and the oil phase was added to the aqueous phase for pre-emulsification, and then uniformly emulsified with a homomixer. Then, by cooling to room temperature with good stirring, a cream considered to be excellent in whitening effect could be prepared.
- Example 38 Cream No. 1 of the composition shown in Table 13. Nos. 1 to 6 and No. Each of the 7 to 10 aqueous phase parts is dissolved by heating to 70 ° C. After preliminarily emulsifying the oil phase by adding the oil phase to the aqueous phase, and then emulsifying with a homomixer, the mixture was cooled to room temperature with good stirring, and a cream considered to have an excellent whitening effect could be prepared.
- Example 39 Lotion No. of the composition shown in Table 14 A lotion could be prepared by mixing the raw materials 1 to 6 with good stirring. Since this skin lotion contains a hydroxypropyl alkylphenyl ether derivative, it is considered that it has an excellent whitening effect and can be suitably used for whitening cosmetics.
Abstract
Description
Rは、-CH2-CHR2-CH2R1又は-CH(CH2R2)-CH2R1を表し、
Raは、-CH2-CHR2-CH2-O-CH2-CHR2-CH2-又は-CH2-CHOH-CH2-を表し、
Rbは、炭素数1~5の、直鎖若しくは分岐状の脂肪族炭化水素基を表し、
R1及びR2は、それぞれ独立に、水素、R8O、R9S、R10R11N、R12A、炭素数1~22の、直鎖若しくは分岐状の、飽和若しくは不飽和の脂肪族炭化水素基、又は、炭素数3~22の飽和若しくは不飽和の環式炭化水素基を表し、
R8、R9、R10、R11及びR12は、それぞれ独立に、炭素数1~22の、直鎖若しくは分岐状の、飽和若しくは不飽和の脂肪族炭化水素基、水酸基で水素が置換されていてもよい炭素数3~22の飽和若しくは不飽和の環式炭化水素基、又は水素を表し、
Aは、リン酸エステル基、硫酸エステル基、エステル基、チオエステル基もしくはアミド基又はこれらの塩を表すが、ただし
R1又はR2の少なくとも一方は水酸基、又はR12A-で表されAがリン酸エステル基、硫酸エステル基若しくはエステル基又はこれらの塩である基であり、かつ
R3、R4、R5、R6及びR7は、それぞれ独立に、
フェニル基で水素が置換されていてもよい炭素数1~12の直鎖若しくは分岐状の、飽和若しくは不飽和の脂肪族炭化水素基、炭素数1~5のアルコキシ基、フェニル基、又は水素を表すが、
R1及びR2が、同時に、水酸基及びR12A-で表されAがリン酸エステル基、硫酸エステル基若しくはエステル基又はこれらの塩である基からなる群より選ばれる基であるときは、R3、R4、R5、R6及びR7の炭素数の合計は2以上である。
構造式(A)で表されるプロピルフェニルエーテル誘導体(請求項13)。
構造式(C)で表されるプロピルフェニルエーテル誘導体(請求項14)。
構造式(E)で表されるプロピルフェニルエーテル誘導体(請求項15)。
構造式(F)で表されるプロピルフェニルエーテル誘導体(請求項16)。
構造式(G)で表されるプロピルフェニルエーテル誘導体(請求項17)。
構造式(H)で表されるプロピルフェニルエーテル誘導体(請求項18)。
構造式(P)で表されるプロピルフェニルエーテル誘導体(請求項19)。
構造式(J)で表されるプロピルフェニルエーテル誘導体(請求項20)。
構造式(K)で表されるプロピルフェニルエーテル誘導体(請求項21)。
1-O-アルキル-2-ヒドロキシ-3-(4’-アルキルフェノキシ)プロピル、
1-O-アルキル-2-ヒドロキシ-3-(2’-アルキルフェノキシ)プロピル、
1-O-アルキル-2-ヒドロキシ-3-(3’-アルキルフェノキシ)プロピル、
1-アルキル-2-ヒドロキシ-3-(4’-アルキルフェノキシ)プロピル、
1-アルキル-2-ヒドロキシ-3-(2’-アルキルフェノキシ)プロピル、
1-アルキル-2-ヒドロキシ-3-(3’-アルキルフェノキシ)プロピル、
1,2-ジ-ヒドロキシ-3-(4’-アルキルフェノキシ)プロピル、
1,2-ジ-ヒドロキシ-3-(2’-アルキルフェノキシ)プロピル、
1,2-ジ-ヒドロキシ-3-(3’-アルキルフェノキシ)プロピル、
1,3-ジ-ヒドロキシ-2-(4’-アルキルフェノキシ)プロピル、
1,3-ジ-ヒドロキシ-2-(2’-アルキルフェノキシ)プロピル、
1,3-ジ-ヒドロキシ-2-(3’-アルキルフェノキシ)プロピル、
1-O-アルキル-3-ヒドロキシ-2-(4’-アルキルフェノキシ)プロピル、
1-O-アルキル-3-ヒドロキシ-2-(2’-アルキルフェノキシ)プロピル、
1-O-アルキル-3-ヒドロキシ-2-(3’-アルキルフェノキシ)プロピル、
1-アルキル-3-ヒドロキシ-2-(4’-アルキルフェノキシ)プロピル、
1-アルキル-3-ヒドロキシ-2-(2’-アルキルフェノキシ)プロピル、
1-アルキル-3-ヒドロキシ-2-(3’-アルキルフェノキシ)プロピル、
1-O-アルキル-2-ヒドロキシ-3-(2’,4’-ジ-アルキルフェノキシ)プロピル、
1-アルキル-2-ヒドロキシ-3-(2’,4’-アルキルフェノキシ)プロピル、
1,2-ジ-ヒドロキシ-3-(2’,4’-アルキルフェノキシ)プロピル、
1,3-ジ-ヒドロキシ-2-(2’,4’-アルキルフェノキシ)プロピル、
1-N-アルキル-2-ヒドロキシ-3-(2’-アルキルフェノキシ)プロピル、
1-N-アルキル-2-ヒドロキシ-3-(3’-アルキルフェノキシ)プロピル、
1-N-アルキル-3-ヒドロキシ-2-(4’-アルキルフェノキシ)プロピル、
1-N-アルキル-3-ヒドロキシ-2-(2’-アルキルフェノキシ)プロピル、
1-N-アルキル-3-ヒドロキシ-2-(3’-アルキルフェノキシ)プロピル、
1-S-アルキル-2-ヒドロキシ-3-(2’-アルキルフェノキシ)プロピル、
1-S-アルキル-2-ヒドロキシ-3-(3’-アルキルフェノキシ)プロピル、
1-S-アルキル-3-ヒドロキシ-2-(4’-アルキルフェノキシ)プロピル、
1-S-アルキル-3-ヒドロキシ-2-(2’-アルキルフェノキシ)プロピル、
1-S-アルキル-3-ヒドロキシ-2-(3’-アルキルフェノキシ)プロピル、
1-アシル-2-ヒドロキシ-3-(2’-アルキルフェノキシ)プロピル、
1-アシル-2-ヒドロキシ-3-(3’-アルキルフェノキシ)プロピル、
1-ホスホリル-2-ヒドロキシ-3-(2’-アルキルフェノキシ)プロピル、
1-ホスホリル-2-ヒドロキシ-3-(3’-アルキルフェノキシ)プロピル、
イソプロピル基、イソブチル基、sec-ブチル基、tert-ブチル基、イソペンチル基、ネオペンチル基、sec-ペンチル基、tert-ペンチル基、イソヘキシル基、ネオヘキシル基、sec-ヘキシル基、tert-ヘキシル基、2-メチルペンチル基、3-メチルペンチル基、2,2-ジメチルブチル基、2-エチルブチル基、イソヘプチル基、イソオクチル基、ネオオクチル基、sec-オクチル基、tert-オクチル基、イソノニル基、イソデシル基、ネオデシル基、sec-デシル基、tert-デシル基、イソウンデシル基、イソドデシル基、イソトリデシルグリシジル基、イソテトラデシル基、イソペンタデシル基、イソヘキサデシル基、イソヘプタデシル基、イソヘキサデシル基、イソオクタデシル基、イソノナデシル基、イソベヘニル基等の分岐鎖アルキル基等を挙げることができる。
4-tert-ブチルフェノール(1.00g)に、水酸化ナトリウム(0.26g)、テトラブチルアンモニウムブロマイド(0.43g)を加え室温にて攪拌し、臭化プロピル(1.64g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.37gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=20/1混液にて溶出し、減圧下にて濃縮を行い、生成物を得た。得られた生成物は、HPTLC分析にて、各原料とは異なるRf値でありUV吸収を有するスポットが確認され、原料から次に示す構造式で表される1-(4’-tert-ブチルフェノキシ)プロピルと考えられる。
4-tert-ブチルフェノール(1.00g)に、水酸化ナトリウム(0.26g)、テトラブチルアンモニウムブロマイド0.43gを加え室温にて攪拌し、臭化エチル(2.20g)を加え、さらに40℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣0.97gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=20/1混液にて溶出し、減圧下にて濃縮を行い、生成物を得た。得られた生成物は、HPTLC分析にてUV吸収のある化合物であることが確認され、原料から次に示す構造式で表される1-(4’-tert-ブチルフェノキシ)エチルと考えられる。
フェニルグリシジルエーテル(1.00g)に、水(5.00g)、DMSO(10.0g)を加え攪拌し、濃硫酸(0.06g)を加え、80℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣0.85gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物を得た。得られた生成物は、HPTLC分析にてUV吸収のある化合物であることが確認され、原料から次に示す構造式で表される1,2-ジ-ヒドロキシ-3-フェノキシプロピルと考えられる。
2-メチルフェノール(1.00g)に、水酸化ナトリウム(0.37g)、テトラブチルアンモニウムブロマイド(0.30g)を加え室温にて攪拌し、グリシドール(0.75g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.49gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=1/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.47g)を得た。得られた生成物は、HPTLC分析にてUV吸収のある化合物であることが確認され、原料から次に示す構造式で表される1,2-ジ-ヒドロキシ-3-(2’-メチルフェノキシ)プロピルと考えられる。
4-tert-ブチルフェノール(1.00g)に、水酸化ナトリウム(0.26g)、テトラブチルアンモニウムブロマイド(0.43g)を加え室温にて攪拌し、グリシドール(0.50g)を加え、さらに室温にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.37gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=1/1混液にて溶出し、減圧下にて濃縮を行い生成物(0.70g)を得た。
1H-NMR(400MHz,CDCl3): δppm 1.29(9H,s),2.49(OH,brs),2.99(OH,brs),3.74(1H,dd),3.83(1H,dd),4.02(2H,m),4.10(1H,m),6.85(2H,d),7.30(2H,d)
13C-NMR(100MHz,CDCl3): δppm 31.4,34.1,63.7,69.1,70.4,113.9,126.3,144.0,156.1
4-tert-ブチルフェノール(1.00g)に、水酸化ナトリウム(0.53g)、テトラブチルアンモニウムブロマイド(0.43g)を加え室温にて攪拌し、プロピレンオキサイド(1.16g)を加え50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.37gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=1/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.20g)を得た。
1H-NMR(400MHz, CDCl3): δppm 1.29(9H,s),1.35(3H,d),1.62(OH,brs),3.93(2H,dd),5.24(1H,m),6.85(2H,d),7.30(2H,d)
13C-NMR(100MHz,CDCl3): δppm 16.7,21.3,31.5,34.1,68.9,70.0,114.1,126.2,143.8,156.3,170.6
4-tert-ブチルフェノール(1.00g)に、水酸化ナトリウム(0.26g)、テトラブチルアンモニウムブロマイド(0.43g)を加え室温にて攪拌し、エチルグリシジルエーテル(0.50g)を加え、さらに室温にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.37gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=1/1混液にて溶出し、減圧下にて濃縮を行い、生成物L(0.35g)及び生成物M(0.03g)を得た。
1H-NMR(400MHz,CDCl3): δppm 1.22(3H,t),1.30(9H,s),3.59(4H,m),4.01(2H,m),4.15(1H,m),6.86(2H,d),7.30(2H,d)
13C-NMR(100MHz CDCl3): δppm 15.1,31.5,34.1,66.9,68.9,69.1,71.3,114.0,126.3,143.8,156.3
1H-NMR(400MHz,CDCl3): δppm 1.25(3H,t),1.30(9H,s),3.71(5H,m),4.03(2H,t-like)6.85(2H,d),7.30(2H,d)
13C-NMR(100MHz CDCl3): δppm 15.7,31.6,34.2,62.7,66.0,67.4,78.0,114.0,126.3,143.8,156.4
4-sec-ブチルフェノール(1.00g)に、水酸化ナトリウム(0.26g)、テトラブチルアンモニウムブロマイド(0.43g)を加え室温にて攪拌し、エチルグリシジルエーテル(0.50g)を加え、さらに室温にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.17gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=1/1混液にて溶出し、減圧下にて濃縮を行い、生成物A(0.38g)及び生成物B(0.04g)を得た。
1H-NMR(400MHz,CDCl3): δppm 0.80(3H,t),1.21(6H,m),1.55(2H,m),2.54(1H,m),3.59(4H,m),4.01(2H,m),4.13(1H,m),6.84(2H,d),7.09(2H,d)
13C-NMR(100MHz,CDCl3): δppm 12.2,15.1,22.0,31.3,40.8,66.9,68.9,69.2,70.5,114.3,128.0,140.5,156.4
4-sec-ブチルフェノール(1.00g)に、水酸化ナトリウム(0.26g)、テトラブチルアンモニウムブロマイド(0.43g)を加え室温にて攪拌し、グリシドール(0.50g)を加え、さらに室温にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.26gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=1/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.65g)を得た。
1H-NMR(400MHz,CDCl3): δppm 0.80(3H,t),1.20(3H,d),1.55(2H,m),2.54(1H,m),3.74(1H,dd),3.83(1H,dd),4.01(1H,m),4.10(1H,m),6.84(2H,d),7.09(2H,d)
13C-NMR(100MHz,CDCl3): δppm 12.2,22.0,31.3,40.8,63.7,69.2,70.5,114.3,128.0,140.5,156.4
2-sec-ブチルフェノール(1.00g)に、水酸化ナトリウム(0.26g)、テトラブチルアンモニウムブロマイド(0.43g)を加え室温にて攪拌し、グリシドール(0.50g)を加え、さらに室温にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.43gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=1/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.65g)を得た。
1H-NMR(400MHz,CDCl3): δppm 0.84(3H,t),1.20(3H,d),1.60(2H,m),2.66(OH,brs)3.06(1H,m),3.78(1H,ddd),3.87(1H,dd),4.05(2H,d),4.14(1H,m),6.85(1H,d),6.96(2H,dt-like),7.16(2H,m)
13C-NMR(100MHz,CDCl3): δppm 12.2,22.5,29.9,33.6,63.9,69.3,70.6,114.5,121.3,126.6,126.9,135.9,155.7
実施例1で得られた、1,2-ジ-ヒドロキシ-3-(4’-tert-ブチルフェノキシ)プロピル(1.00g)に、DMF7mL、トリエチルアミン(0.30g)を加え室温にて攪拌し、n-カプリル酸無水物(0.80g)を加えた。80℃にて2時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.97gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=5/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.65g)を得た。
1H-NMR(400MHz,CDCl3): δppm 0.88(6H,m),1.30(25H,s),1.63(4H,m),2.36(4H,m),4.01(2H,m),4.26(3H,m),6.85(2H,d),7.31(2H,d)
13C-NMR(100MHz,CDCl3): δppm 14.1,22.6,24.7,24.9,29.0,29.07,29.13,34.09,34.14,34.20,65.2,68.7,68.65,68.70,114.0,126.4,144.1,156.1,174.2,179.8
エピクロロヒドリン(1.00g)に、水酸化ナトリウム(0.43g)、テトラブチルアンモニウムブロマイド(0.43g)を加え室温にて攪拌し、4-tert-ブチルフェノール(1.96g)を加え、さらに室温にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.87gに、テトラブチルアンモニウムブロマイド(0.19g)、水酸化ナトリウム(0.24g)を加え、4-tert-ブチルフェノール(1.96g)を加えた。80℃にて2時間攪拌したあと、酢酸エチル、水を加え抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下に濃縮をし得られた残渣2.56gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=10/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.48g)を得た。
1H-NMR(400MHz,CDCl3): δppm 1.30(18H,s),1.63(OH,brs),2.64(OH,brs),4.13(4H,m),4.17(1H,m),6.87(4H,m),7.28(4H,d)
13C-NMR(100MHz,CDCl3): δppm 31.4,34.1,68.7,68.8,114.0,126.3,143.9,156.1
エピクロロヒドリン(1.00g)に、水酸化ナトリウム(0.43g)、テトラブチルアンモニウムブロマイド(0.43g)を加え室温にて攪拌し、4-tert-ブチルフェノール(1.96g)を加えた。さらに室温にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.87gに、テトラブチルアンモニウムブロマイド(0.19g)、水酸化ナトリウム(0.24g)を加え、ハイドロキノン(1.43g)を加え、80℃にて2時間攪拌したあと、酢酸エチル、水を加え抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下に濃縮をし得られた残渣2.56gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=3/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.27g)を得た。
1H-NMR(400MHz,CDCl3): δppm 1.30(9H,s),1.64(OH,brs),2.64(OH,brs),4.10(4H,m),4.13(1H,brs),6.81(4H,m),7.31
13C-NMR(100MHz,CDCl3): δppm 31.5,34.1,68.7,68.8,69.4,114.0,115.5,126.3,144.0,153.0,156.1
エピクロロヒドリン(1.00g)に、水酸化ナトリウム(0.43g)、テトラブチルアンモニウムブロマイド0.43gを加え室温にて攪拌し、4-tert-ブチルフェノール(1.96g)を加え、さらに室温にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.87gに、テトラブチルアンモニウムブロマイド(0.19g)、水酸化ナトリウム(0.24g)を加え、実施例1で得られた1,2-ジ-ヒドロキシ-3-(4’-tert-ブチルフェノキシ)プロピル(2.19g)を加え、80℃にて2時間攪拌したあと、酢酸エチル、水を加え抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下に濃縮をし得られた残渣2.56gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=5/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.35g)を得た。
1H-NMR(400MHz,CDCl3): δppm 1.29(18H,s),1.67(OH,brs),2.82(OH,brs),3.28(OH,brs),3.71(2H,m),3.85(2H,m),3.98(4H,m),4.14(2H,m),6.84(4H,m),7.29(4H,m)
13C-NMR(100MHz,CDCl3): δppm 31.5,34.1,67.7,67.8,68.5,68.7,69.08,69.15,69.18,69.42,71.5,71.6,72.1,72.4,72.7,114.0,126.24,126.29,143.7,143.8,143.9,156.1,156.2,156.3
エピクロロヒドリン(1.00g)に、水酸化ナトリウム(0.43g)、テトラブチルアンモニウムブロマイド0.43gを加え室温にて攪拌し、4-tert-ブチルフェノール(1.96g)を加え、さらに室温にて5時間攪拌したあと、酢酸エチル、水を加え抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.87gに、セチルアルコール(3.16g)、濃硫酸(0.21g)を加え、80℃にて24時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣3.02gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.30g)を得た。
1H-NMR(400MHz, CDCl3): δppm 0.86(9H,t),1.24,1.28(35H,s),1.56(2H,m),3.46(2H,m),3.56(2H,m),3.99(2H,m),4.13(1H,m),6.84(2H,d),7.28(2H,d)
13C-NMR(100MHz,CDCl3): δppm 14.1,22.7,26.1,29.3,29.5,29.6,29.7,31.5,31.9,34.0,68.9,69.1,71.4,71.7,114.0,126.2,143.7,156.3
4-n-ブチルフェノール(1.00g)に、水酸化ナトリウム(0.26g)、テトラブチルアンモニウムブロマイド(0.43g)を加え室温にて攪拌し、グリシドール(0.50g)を加えた。さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.28gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.58g)を得た。
1H-NMR(400MHz, CDCl3): δppm 0.90(3H,t),1.32(2H,m),1.54(2H,m),2.52(2H,t),3.71(1H,dd),3.80(1H,dd),3.98(2H,m),4.07(1H,m),6.80(2H,d),7.06(2H,d)
13C-NMR(100MHz,CDCl3): δppm 13.9,22.2,33.8,34.7,63.7,69.1,70.4,114.3,129.3,135.7,156.3
4-イソプロピルフェノール(1.00g)に、水酸化ナトリウム(0.29g)、テトラブチルアンモニウムブロマイド(0.24g)を加え室温にて攪拌し、グリシドール(0.60g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.38gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.53g)を得た。
1H-NMR(400MHz, CDCl3): δppm 1.20(6H,d),2.84(1H,m),3.72(1H,dd),3.81(1H,dd),3.99(2H,d-like),4.08(1H,m),6.82(2H,d),7.12(2H,d)
13C-NMR(100MHz,CDCl3): δppm 24.1,33.2,63.7,69.2,70.4,114.3,127.3,141.7,156.4
4-エチルフェノール(1.00g)に、水酸化ナトリウム(0.33g)、テトラブチルアンモニウムブロマイド(0.26g)を加え室温にて攪拌し、グリシドール(0.67g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.26gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.40g)を得た。
1H-NMR(400MHz, CDCl3): δppm 1.18(3H,s),2.57(2H,d),3.72(1H,dd),3.81(1H,dd),3.99(1H,brd),4.07(1H,brd),6.81(2H,d),7.08(2H,d)
13C-NMR(100MHz,CDCl3): δppm 15.8,27.9,63.7,69.2,70.4,114.4,128.8,137.1,156.3
4-tert-アミルフェノール(1.00g)に、水酸化ナトリウム(0.24g)、テトラブチルアンモニウムブロマイド(0.20g)を加え室温にて攪拌し、グリシドール(0.50g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.22gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.50g)を得た。
1H-NMR(400MHz, CDCl3): δppm 0.65(3H,t),1.35(9H,m),1.59(1H,q),3.58(4H,m),4.00(2H,m),4.15(1H,m),6.84(2H,d),7.22(2H,d)
13C-NMR(100MHz,CDCl3): δppm 9.1,15.1,28.6,36.9,37.3,66.9,68.9,69.1,71.3,113.9,126.9,142.0,156.2
4-α-クミルフェノール(1.00g)に、水酸化ナトリウム(0.19g)、テトラブチルアンモニウムブロマイド(0.15g)を加え室温にて攪拌し、グリシドール(0.38g)を加えた。さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.05gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い生成物(0.31g)を得た。
1H-NMR(400MHz, CDCl3): δppm 1.66(6H,s),(1H,m),3.73(1H,dd),3.83(1H,dd),4.01(2H,m),4.10(1H,m),6.81(2H,d),7.16(3H,m),7.25(4H,m)
13C-NMR(100MHz,CDCl3): δppm 30.8,42.3,63.7,69.1,70.4,113.9,125.6,126.7,127.86,127.94,143.6,150.7,156.2
4-(1,1,3,3-テトラメチルブチル)フェノール(1.00g)に、水酸化ナトリウム(0.19g)、テトラブチルアンモニウムブロマイド(0.15g)を加え室温にて攪拌し、グリシドール(0.40g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.10gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.40g)を得た。
1H-NMR(400MHz, CDCl3): δppm 0.70(9H,s),1.22(3H,m),1.33(3H,s),1.69(2H,s),3.58(4H,m),4.00(2H,m),4.15(1H,m),6.83(2H,d),7.26(2H,d)
13C-NMR(100MHz,CDCl3): δppm 15.1,31.6,31.7,32.3,37.9,56.9,66.9,68.9,69.1,71.3,113.7,127.1,142.6,156.2
4-tert-ブチルフェノール(1.00g)に、水酸化ナトリウム(0.19g)、テトラブチルアンモニウムブロマイド(0.21g)を加え室温にて攪拌し、3-ブロモ-1-ヒドロキシプロピル(1.02g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.98gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.38g)を得た。
2,6-ジ-sec-ブチルフェノール(1.00g)に、水酸化ナトリウム(0.19g)、テトラブチルアンモニウムブロマイド(0.16g)を加え室温にて攪拌し、グリシドール(0.40g)を加えた。さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.24gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=3/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.17g)を得た。
2,4-ジ-tert-ブチルフェノール(1.00g)に、水酸化ナトリウム(0.19g)、テトラブチルアンモニウムブロマイド(0.16g)を加え室温にて攪拌し、グリシドール(0.40g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.15gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.31g)を得た。
1H-NMR(400MHz, CDCl3): δppm 1.29(9H,s),1.38(9H,s),3.77(1H,dd),3.88(1H,dd),4.05(2H,m),4.18(1H,m),6.80(1H,d),7.16(1H,m),7.32(1H,d)
13C-NMR(100MHz,CDCl3): δppm 30.0,31.5,34.3,35.0,64.0,68.9,70.8,111.5,123.5,124.1,137.1,143.2,154.8
2,4-ジ-tert-ブチル-5-メチルフェノール(1.00g)に、水酸化ナトリウム(0.18g)、テトラブチルアンモニウムブロマイド(0.15g)を加え室温にて攪拌し、グリシドール(0.34g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.20gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.27g)を得た。
1H-NMR(400MHz,CDCl3): δppm 1.36(21H,brs),3.76(1H,dd),3.87(1H,dd),4.06(2H,m),4.16(1H,m),6.63(1H,s),7.29(1H,s)
13C-NMR(100MHz,CDCl3): δppm 22.8,30.1,31.1,34.8,35.5,64.0,68.9,70.8,116.5,125.1,134.2,134.8,140.0,154.4
2,6-ジ-tert-ブチル-4-メチルフェノール(1.00g)に、水酸化ナトリウム(0.18g)、テトラブチルアンモニウムブロマイド(0.15g)を加え室温にて攪拌し、グリシドール(0.34g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.15gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い生成物(0.31g)を得た。
2-tert-ブチル-4-メトキシフェノール(1.00g)に、水酸化ナトリウム(0.22g)、テトラブチルアンモニウムブロマイド(0.18g)を加え室温にて攪拌し、グリシドール(0.45g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.39gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.50g)を得た。
3-tert-ブチル-4-メトキシフェノール(1.00g)に、水酸化ナトリウム(0.22g)、テトラブチルアンモニウムブロマイド(0.18g)を加え室温にて攪拌し、グリシドール(0.45g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.20gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.41g)を得た。
2,2-ビス(4-グリシジルオキシフェニル)プロパン(1.00g)に、水(5.0g)、DMSO(10.0g)を加え室温にて攪拌し、濃硫酸(0.06g)を加え、さらに80℃にて2時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.54gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=3/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.40g)を得た。
2-エチルヘキシルグリシジルエーテル(1.00g)に、水酸化ナトリウム(0.22g)、テトラブチルアンモニウムブロマイド(0.17g)を加え室温にて攪拌し、2-sec-ブチルフェノール(0.89g)を加え、さらに室温にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.67gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.10g)を得た。
2-sec-ブチルフェノール(1.00g)に、水酸化ナトリウム(0.27g)、テトラブチルアンモニウムブロマイド(0.22g)を加え室温にて攪拌し、エチルグリシジルエーテル(0.75g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.69gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.54g)を得た。
1H-NMR(400MHz, CDCl3): δppm 0.83(3H,t),1.23(6H,m),1.57(2H,m),3.07(1H,m),3.59(4H,m),4.01(2H,d-like),4.17(1H,m),6.84(1H,d),6.93(1H,t-like),7.14(2H,m)
13C-NMR(100MHz,CDCl3): δppm 12.2,15.1,20.4,29.9,33.6,66.9,68.9,69.2,71.4,111.5,121.0,126.5,126.8,135.9,155.9
4-クミルフェノール(1.00g)に、水酸化ナトリウム(0.19g)、テトラブチルアンモニウムブロマイド(0.15g)を加え室温にて攪拌し、エチルグリシジルエーテル(0.53g)を加え50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.50gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.47g)を得た。
1H-NMR(400MHz, CDCl3): δppm 1.22(3H,t),1.66(6H,m),3.58(4H,m),4.00(2H,m),4.15(1H,m),6.84(2H,d),7.16(3H,m),7.25(4H,m)
13C-NMR(100MHz,CDCl3): δppm 15.1,30.8,42.3,66.9,68.9,69.1,71.3,113.9,125.5,126.7,127.8,127.9,143.3,150.8,156.4
3-メチル-4-イソプロピルフェノール(1.00g)に、水酸化ナトリウム(0.27g)、テトラブチルアンモニウムブロマイド(0.22g)を加え室温にて攪拌し、エチルグリシジルエーテル(0.75g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.60gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.74g)を得た。
1H-NMR(400MHz, CDCl3): δppm 1.22(9H,t),2.92(3H,s),3.05(1H,m),3.57(4H,m),3.98(2H,m),4.13(1H,m),6.72(2H,d),7.13(1H,d)
13C-NMR(100MHz,CDCl3): δppm 15.1,19.4,23.4,28.6,66.9,68.8,69.1,71.3,111.8,116.4,125.6,136.4,139.5,156.2
2,6-ジ-sec-ブチルフェノール(1.00g)に、水酸化ナトリウム(0.19g)、テトラブチルアンモニウムブロマイド(0.16g)を加え室温にて攪拌し、エチルグリシジルエーテル(0.54g)を加え50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.31gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.39g)を得た。
1H-NMR(400MHz, CDCl3): δppm 0.82(6H,m),1.23(9H,s),1.59(4H,s),2.51(1H,m),3.03(1H,m),3.56(3H,m),3.64(1H,dd),3.99(2H,d-like),4.16(1H,m),6.77(1H,d),6.93(2H,d)
13C-NMR(100MHz,CDCl3): δppm 12.2,15.1,20.4,21.9,22.0,29.8,31.3,31.4,33.8,41.0,66.9,69.0,69.3,71.5,111.3,111.29,111.32,124.4,124.5,125.6,125.8,135.4,140.1,153.9
3-メチル-4-イソプロピルフェノール(1.00g)に、水酸化ナトリウム(0.27g)、テトラブチルアンモニウムブロマイド(0.22g)を加え室温にて攪拌し、グリシドール(0.75g)を加え50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.54gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=1/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.68g)を得た。
1H-NMR(400MHz, CDCl3): δppm 1.18(6H,d),2.29(3H,s),3.05(1H,m),3.72(1H,dd),3.81(1H,dd),3.99(2H,m),4.09(1H,m),6.71(1H,2m),7.14(1H,d)
13C-NMR(100MHz,CDCl3): δppm 19.4,23.4,63.7,69.1,70.4,111.8,116.3,125.7,136.5,139.8,155.9
2,2-ビス(4-グリシジルオキシフェニル)プロパン(1.00g)に、エタノール(0.14)及び濃硫酸(0.03g)を加え、50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.04gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=1/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.29g)を得た。
1H-NMR(400MHz, CDCl3): δppm 1.19(6H,t),1.61(6H,s),2.50(4H,s),3.56(8H,m),3.99(4H,m),4.13(2H,m),6.80(2H,d),7.11(2H,d)
13C-NMR(100MHz,CDCl3): δppm 15.1,31.0,41.7,68.9,69.0,71.3,113.9,127.7,143.5,156.3
4-(1,1,3,3-テトラメチルブチル)フェノール(1.00g)に、水酸化ナトリウム(0.19g)、テトラブチルアンモニウムブロマイド(0.15g)を加え室温にて攪拌し、エチルグリシジルエーテル(0.55g)を加え、さらに50℃にて5時間攪拌したあと、酢酸エチル、水を加え酢酸エチルで目的物を抽出した。抽出液を無水硫酸ナトリウムで乾燥後、減圧下で濃縮して得られた残渣1.23gをシリカゲルカラムクロマトグラフィーに付した。ヘキサン/酢酸エチル=2/1混液にて溶出し、減圧下にて濃縮を行い、生成物(0.31g)を得た。
1H-NMR(400MHz, CDCl3): δppm 0.70(9H,s),1.22(3H,m),1.33(3H,s),3.58(4H,m),4.00(2H,m),4.15(1H,m),6.83(2H,d),7.26(2H,d)
13C-NMR(100MHz,CDCl3): δppm 15.1,31.6,31.7,32.3,37.9,56.9,66.9,68.9,69.1,71.3,113.7,127.1,142.6,156.2
下記の手順によって、B16メラノーマ4A5細胞のテオフィリン誘発メラニン生成に対する作用の評価を、本発明のプロピルフェニルエーテル誘導体、及び合成例1~4で得られた化合物やアルブチン等の比較品について行った。その結果を表1~3に示す。
(2)10%ウシ胎児血清(ニチレイバイオサイエンス社製)含有ダルベッコ変法イーグル培地(SIGMA社製、以下D-MEMと略記する)にて24時間培養後、終濃度が1.0mmol/Lになるように調整したテオフィリンを含有した10%ウシ胎児血清含有D-MEM及び終濃度が所定の濃度になるように調整した試料を含有した10%ウシ胎児血清含有D-MEMを添加した。
(3)試料共存下で3日間培養後、アスピレーターを用いて培地を除去し、蒸留水を添加後、超音波により細胞を破砕した。
[アルカリ可溶化法]
細胞破砕液に終濃度1mol/Lとなるように水酸化ナトリウムを添加して加熱溶解(60℃、30分)後、マイクロプレートリーダーを用いて405nmの吸光度を測定した。メラニン量は、合成メラニン(SIGMA)を標準品として作成した検量線から算出した。タンパク質量でメラニン量を除することにより単位タンパク質あたりのメラニン量を算出した。
メラニン産生抑制率(%)=[1-(A-B)/(C-B)]×100
[式中、Aは、試料添加時の単位タンパク質あたりのメラニン量(g/g)、Bは、Normal群の単位タンパク質あたりのメラニン量(g/g)、CはControl群の単位タンパクあたりのメラニン量(g/g)を示す。]
メラニン産生抑制率を40%以上とするために必要とした試料の量を求め、その量に基づき下記の基準で評価した。なお、測定はN=4(1試料につき4well)で行った。メラニン生成抑制率が40%以上を示すサンプル濃度に基づき、美白効果を下記のように表記し、その結果を表1~3に示す。なお、測定はN=4で行った。
≧300μmol/L :△
100~300μmol/L :○
30~100μmol/L :◎
≦30μmol/L :◎◎
大腸菌(Escherichia coli)、緑濃菌(Pseudomonas aeruginosa)、黄色ブドウ球菌(Staphylococcus aureus)、及びカンジダ菌(Candida albicans)の4種の菌(ATCC株を使用)を用いて、下記の手順により本発明のプロピルフェニルエーテル誘導体について抗菌性試験の評価を行った。比較品として、1,2-ペンタンジオールを用いた。
(2)その後、(1)で作製したサンプルを含む培地に、予め菌数が1.0×104~5.0×104cfu/mLとなるように調製しておいた各種菌液を、シャーレの1区分に1菌種ずつ、4箇所に各々10μLずつ接種した。(すなわち、1サンプルに4種の菌について3濃度となるので、1サンプルあたり12検体となる。)
(3)30℃の恒温槽で7日間培養を行った。
(4)肉眼により菌の有無の判定を行った。
菌が確認された検体数が、10検体以上であった:△
菌が確認された検体数が、6~9であった: ○
菌が確認された検体数が、5以下であった: ◎
Propionibacterium acnes(JCM6415:ATCC株)をGAMブイヨン培地(日水製薬社製)に移植し、37℃、嫌気条件下で24時間培養した。その後、GAMブイヨン培地で希釈し、終菌体濃度がOD620=0.1になるように調製し、これを試験菌液とした。実施例のプロピルフェニルエーテル誘導体は、終濃度が0.1%になるように秤量し、GAMブイヨン培地に溶解した後、濾過滅菌を行い、これを試料溶液とした。96穴マイクロプレート(住友ベークライト社製)に試験菌液を30μL、試料溶液を120μL添加した後、直ちに嫌気ジャー(三菱ガス化学社製)にマイクロプレートとアネロパック・ケンキ(三菱ガス化学社製)を入れ、37℃、嫌気条件下で48時間培養を行った。その後、マイクロプレートリーダーにより、OD620を測定した。なお、比較品として、メチルパラベン、フェノキシエタノール、アスコルビン酸ナトリウムを用いて同様の試験を行った。
△:OD620=0.6以上
○:OD620=0.3~0.6
◎:OD620=0.3以下
実施例1の1,2-ジ-ヒドロキシ-3-(4’-tert-ブチルフェノキシ)プロピルを用いて、50℃で4週間保管したときの着色について安定性を下記の要領で評価した。比較品には、公知な美白剤である、アスコルビン酸、コウジ酸、ハイドロキノン、アルブチンを用いた。
2: 調製直後と比較して着色する
1: 調製直後と比較して強く着色
○:10人の総合点が22以上
△:10人の総合点が15~21
×:10人の総合点が14以下
表9に示す組成のNo.1~6の油相部の原料、及びNo.7~10の水相部の原料をそれぞれ70℃に加温し溶解して、油相および水相をそれぞれ調製した。その後、水相に油相を加え予備乳化を行い、ホモミキサーで均一に乳化した後、よく攪拌しながら室温まで冷却することにより、美白効果に優れると考えられるクリームを調製することができた。なお、表9以後の表中の配合量は質量部を表す。
表10に示す組成のNo.1~10の油相部の原料、及びNo.11~13の水相部の原料をそれぞれ70℃に加温し溶解して、油相および水相をそれぞれ調製した。その後、水相に油相を加え予備乳化を行いホモミキサーで均一に乳化した後、よく攪拌しながら室温まで冷却することにより、美白効果に優れると考えられる乳液を調製することができた。
表11に示す組成のNo.4~10の油相部の原料、及びNo.1~3、11~12の水相部の原料をそれぞれ70℃に加温し溶解して、油相および水相をそれぞれ調製した。その後、水相に油相を加え予備乳化を行い、ホモミキサーで均一に乳化した後、よく攪拌しながら室温まで冷却することにより、美白効果に優れると考えられる乳液を調製することができた。
表12に示す組成のNo.1~3の油相部の原料、及びNo.4~10の水相部の原料をそれぞれ70℃に加温し溶解して、油相および水相をそれぞれ調製した後、水相に油相を加え予備乳化を行い、ホモミキサーで均一に乳化した後、よく攪拌しながら室温まで冷却することにより、美白効果に優れると考えられるクリームを調製することができた。
表13に示す組成のNo.1~6の油相部を、およびNo.7~10の水相部をそれぞれ70℃に加温溶解する。水相部に油相部を加え予備乳化を行い、ついでホモミキサーで乳化した後、よく攪拌しながら室温まで冷却し、美白効果に優れると考えられるクリームを調製することができた。
表14に示す組成のNo.1~6の原料を、よく攪拌しながら混合することにより、化粧水を調製することができた。この化粧水は、ヒドロキシプロピルアルキルフェニルエーテル誘導体を含むため、美白効果に優れ美白化粧料に好適に使用できると考えられる。
Claims (27)
- 下記一般式(I)、(Ia)又は(Ib)で表されることを特徴とするプロピルフェニルエーテル誘導体:
[式(I)、(Ia)又は(Ib)中、
Rは、-CH2-CHR2-CH2R1又は-CH(CH2R2)-CH2R1を表し、
Raは、-CH2-CHR2-CH2-O-CH2-CHR2-CH2-又は-CH2-CHOH-CH2-を表し、
Rbは、炭素数1~5の、直鎖若しくは分岐状の脂肪族炭化水素基を表し、
R1及びR2は、それぞれ独立に、水素、R8O、R9S、R10R11N、R12A、炭素数1~22の、直鎖若しくは分岐状の、飽和若しくは不飽和の脂肪族炭化水素基、又は、炭素数3~22の飽和若しくは不飽和の環式炭化水素基を表し
R8、R9、R10、R11及びR12は、それぞれ独立に、炭素数1~22の、直鎖若しくは分岐状の、飽和若しくは不飽和の脂肪族炭化水素基、水酸基で水素が置換されていてもよい炭素数3~22の飽和若しくは不飽和の環式炭化水素基、又は水素を表し、
Aは、リン酸エステル基、硫酸エステル基、エステル基、チオエステル基もしくはアミド基又はこれらの塩を表すが、ただし
R1又はR2の少なくとも一方は水酸基、又はR12A-で表されAがリン酸エステル基、硫酸エステル基若しくはエステル基又はこれらの塩である基であり、かつ
R3、R4、R5、R6及びR7は、それぞれ独立に、
フェニル基で水素が置換されていてもよい炭素数1~12の直鎖若しくは分岐状の、飽和若しくは不飽和の脂肪族炭化水素基、炭素数1~5のアルコキシ基、フェニル基、又は水素を表すが、
R1及びR2が、同時に、水酸基及びR12A-で表されAがリン酸エステル基、硫酸エステル基若しくはエステル基又はこれらの塩である基からなる群より選ばれる基であるときは、R3、R4、R5、R6及びR7の炭素数の合計は2以上である。] - R1又は/及びR2が、水素、炭素数1~22の、直鎖若しくは分岐状の、飽和若しくは不飽和の脂肪族炭化水素基、R8O、R9S及びR10R11Nから選ばれる基であることを特徴とする請求項1に記載のプロピルフェニルエーテル誘導体。
- R1がR8Oであり、R2が水酸基であることを特徴とする請求項2に記載のプロピルフェニルエーテル誘導体。
- 一般式(I)で表されることを特徴とする請求項3に記載のプロピルフェニルエーテル誘導体。
- R8が水素又は炭素数1~22の、直鎖若しくは分岐状の、飽和若しくは不飽和の脂肪族炭化水素基であることを特徴とする請求項4に記載のプロピルフェニルエーテル誘導体。
- R8が炭素数1~22の、直鎖若しくは分岐状の、飽和若しくは不飽和の脂肪族炭化水素基であることを特徴とする請求項5に記載のプロピルフェニルエーテル誘導体。
- 一般式(I)で表され、R3、R4、R5、R6及びR7が、それぞれ独立に、水素、又は、炭素数1~12の、直鎖若しくは分岐状の、飽和若しくは不飽和の脂肪族炭化水素であることを特徴とする請求項1ないし請求項6のいずれか1項に記載のプロピルフェニルエーテル誘導体。
- R3、R4、R5、R6及びR7の少なくとも1つの基が、分岐状の脂肪族炭化水素であり、かつR3、R4、R5、R6及びR7の炭素数の合計が4以上であることを特徴とする請求項7に記載のプロピルフェニルエーテル誘導体。
- R3、R4、R5、R6及びR7の少なくとも1つの基が、tert-ブチル基又はsec-ブチル基であることを特徴とする請求項8に記載のプロピルフェニルエーテル誘導体。
- 一般式(Ia)で表され、Raが-CH2-CH(OH)-CH2-であることを特徴とする請求項1に記載のプロピルフェニルエーテル誘導体。
- 一般式(Ib)で表され、Rbが-C(CH3)2-であることを特徴とする請求項1に記載のプロピルフェニルエーテル誘導体。
- 請求項1ないし請求項21のいずれか1項に記載のプロピルフェニルエーテル誘導体を有効成分として配合することを特徴とするメラニン生成抑制剤。
- 請求項1ないし請求項21のいずれか1項に記載のプロピルフェニルエーテル誘導体を有効成分として配合することを特徴とする美白剤。
- 請求項1ないし請求項21のいずれか1項に記載のプロピルフェニルエーテル誘導体を有効成分として配合することを特徴とする抗菌剤。
- 請求項1ないし請求項21のいずれか1項に記載のプロピルフェニルエーテル誘導体を配合することを特徴とする化粧料。
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- 2013-10-31 WO PCT/JP2013/079498 patent/WO2014069555A1/ja active Application Filing
- 2013-10-31 JP JP2014521386A patent/JP5750773B2/ja active Active
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JPWO2014069555A1 (ja) | 2016-09-08 |
JP5830742B2 (ja) | 2015-12-09 |
JP5750773B2 (ja) | 2015-07-22 |
BR112015008936A2 (pt) | 2017-07-04 |
US20150238401A1 (en) | 2015-08-27 |
KR20150074160A (ko) | 2015-07-01 |
JP2014139253A (ja) | 2014-07-31 |
CN104755452A (zh) | 2015-07-01 |
EP2915796A4 (en) | 2016-04-20 |
EP2915796A1 (en) | 2015-09-09 |
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