JP5473343B2 - Serotonin compounds, tyrosinase inhibitors and whitening cosmetics - Google Patents

Description

  The present invention relates to a serotonin compound having tyrosinase inhibitory activity, a tyrosinase inhibitor containing the compound as an active ingredient, and a whitening cosmetic.

  Spots, freckles, and pigmentation on the skin after sunburn become difficult to occur, increase, or disappear with aging, which is a problem for middle-aged and elderly people. Although the onset mechanism of these pigmentation diseases has not yet been elucidated, it is considered that the mechanism of melanin synthesis of epidermal melanocytes is enhanced by the action of sunlight, particularly ultraviolet rays and melanocyte stimulating hormone.

  In addition, the keratinization delay associated with aging of epidermal keratinocytes (keratinocytes) also delays the rate of melanin excretion outside the epidermis, and together with the enhancement of melanin synthesis capacity, the increase in melanin granule density in the epidermis, ie clinical It is thought that the symptom that the pigmentation increases is developed. In addition, these pigmented areas are present locally and may cause a clear difference from the surrounding normal skin color.

  Therefore, a drug that restores the acquired pigmented part to normal skin color and a drug that prevents pigmentation are strongly desired, and many drugs have been developed and commercialized so far. .

  For example, in recent years, cosmetics using vitamin C (L-ascorbic acid) derivatives having excellent reducing ability have been proposed, but vitamin C derivatives have difficulty in stability, and are almost effective for external use. Not.

  In Europe and the United States, hydroquinone is used as a medicine for the treatment of stains and whitening of black skin, but hydroquinone has its own safety (irritant, allergic), There is a problem in blending it into a general-purpose drug from the viewpoint that it may cause vitiligo.

  In addition to these, various substances that show efficacy in an in vitro tyrosinase activity inhibition test have been reported as melanin inhibitors. Among them, for benzoic acid derivatives, in vitro tyrosinase activity inhibition and whitening action have been reported for salicylic acid derivatives having a short-chain alkoxy group (see Patent Document 1). However, even with known melanin inhibitors such as short-chain alkoxy-substituted salicylic acid derivatives as reported, a sufficient whitening effect is not yet obtained, and furthermore, safety such as skin irritation is not sufficient. .

  That is, a compound that sufficiently satisfies both the pigmentation improving (whitening) effect and the safety to the skin has not been proposed yet, and is currently strongly demanded.

  By the way, Non-Patent Document 1 includes N-feruloyl serotonin extracted from safflower seeds, N- (p-coumaroyl) serotonin (N- (p-coumaroyl) serotonin), and the like. Has been shown to potently inhibit melanin production.

Biol. Pharm. Bull. 27 (12) 1976-1978 (2004)

  An object of the present invention is to provide a compound having tyrosinase inhibitory activity. Another object of the present invention is to provide a tyrosinase inhibitor containing the compound as an active ingredient. Furthermore, it is providing the whitening cosmetics excellent in the whitening effect, such as preventing or improving the deposition of the abnormal melanin pigment on the epidermis of mammals.

  As a result of intensive studies to achieve the above-mentioned object, the present inventor has found that the extract of Misotake has an excellent tyrosinase inhibitory action, and further develops this to complete the present invention. It came.

  That is, the present invention relates to the following serotonin derivatives, tyrosinase inhibitors and whitening cosmetics.

  Item 1. Formula (I):

(In the formula, R is the same or different and represents an alkyl group.)
Or a salt thereof.

  Item 2. Item 2. The compound according to item 1, wherein in general formula (I), R is the same or different and is an alkyl group having 1 to 3 carbon atoms.

  Item 3. Item 3. A tyrosinase inhibitor comprising the compound according to Item 1 or 2 as an active ingredient.

  Item 4. Item 10. A whitening cosmetic comprising the compound according to Item 1 or 2 as an active ingredient.

  Item 5. Formula (I):

(In the formula, R is the same or different and represents an alkyl group.)
Wherein the compound represented by the general formula (II):

(Wherein R is the same as above)
And a compound represented by the general formula (III):

A production method comprising the step of subjecting a serotonin represented by the formula or a derivative thereof to a condensation reaction.

  Item 6. A whitening cosmetic that contains an extract of Miso bamboo.

  Item 7. Item 7. The whitening cosmetic composition according to Item 6, which contains, as an active ingredient, an extract obtained by extracting 孟宗竹 with at least one selected from the group consisting of alcohol and ethyl acetate.

  The serotonin compound of the present invention has an excellent tyrosinase inhibitory activity and a high whitening effect. Therefore, it is useful as a whitening cosmetic.

The extraction process from Miso bamboo and the insoluble part of various solvents are shown. It is a graph which shows the relationship between the density | concentration of each inversion part, and a tyrosinase inhibitory activity rate. The process of refine | purifying the compounds 1 and 2 from an ethyl acetate transfer part is shown. It is a graph which shows the relationship between the concentration of ethyl acetate transfer part, the fractions 1 and 2, and the tyrosinase inhibitory activity rate. It is a graph which shows the relationship between the density | concentration of compounds 1-5 and arbutin, and a tyrosinase inhibitory activity rate. The structure of compound 1 and various spectral data are shown. The structure of compound 2 and various spectral data are shown. The structure of compound 3 and various spectral data are shown. The structure of compound 4 and various spectral data are shown. The structure of compound 5 and various spectral data are shown.

  The tyrosinase inhibitor of the present invention comprises, as an active ingredient, an extract from Miso bamboo, particularly a compound represented by the general formula (I).

Extract from Sosou bamboo Sosou bamboo can be used for extraction as it is, but it is preferable to use it after it is pulverized more finely.

  There are no particular limitations on the extraction solvent of Munetake, for example, alcohols such as methanol, ethanol, propanol and butanol; glycols such as 1,3-butylene glycol, glycerin and propylene glycol; ethyl acetate, butyl acetate and the like Esters; hydrocarbons such as hexane, cyclohexane, petroleum ether; water and the like can be used. These extraction solvents can be used singly or in combination of two or more. In particular, the use of at least one selected from the group consisting of alcohols such as methanol and ethanol and esters such as ethyl acetate and butyl acetate is easy to handle and provides an extract having excellent activity. It is preferable in that it can be performed. In this case, particularly when the extract is used as a whitening cosmetic, it is preferable to use ethanol as the alcohol.

  In the case of using a mixture of solvents, the mixing ratio of each solvent may be appropriately adjusted according to the type of the solvent. For example, when used as a mixed solution of water and alcohol, water: alcohol (weight) Ratio) = 1: 100 to about 100: 1, preferably about 1:50 to 50: 1, and more preferably used at approximately equal weight.

  The extraction method is not particularly limited, and a heating extraction method in which heating is performed to such an extent that the tyrosinase inhibitory activity of the extract is not deactivated after adding a solvent to Somune bamboo, a supercritical extraction method, etc. are appropriately applied. it can. Moreover, various well-known extraction methods, such as the immersion extraction method which carries out batch processing by immersing Miso bamboo in a fixed amount of solvent, and the continuous extraction method which continues sending a solvent continuously, are applicable.

  An example of a specific extraction method includes, for example, about 0.5 to 5 times by weight, preferably about 0.8 to 1.2 times by weight extraction solvent, and soaked with respect to the dry weight of Miso bamboo. Then, by heating and refluxing the solvent for about 30 to 60 minutes, a component having tyrosinase inhibitory activity can be extracted. Of course, the amount of the solvent, the heating temperature, the heating time, and the like may be appropriately adjusted so that a component having excellent tyrosinase inhibitory activity can be extracted.

  An extract can be obtained by obtaining an extract from Somune bamboo by the above-mentioned method and then solid-liquid separating the residue from the residue by conventional methods such as filtration and centrifugation. In the present invention, the obtained extract can be used as it is as a tyrosinase inhibitor. However, since the activity may be low, it may be used as an extract or a powder by appropriately concentrating or distilling off the solvent. it can.

  Further, the active fraction is separated from the extracted fraction obtained by solvent fractionation operation using one or more organic solvents such as methanol, ethanol, propanol, butanol, chloroform, ethyl acetate, toluene, hexane, benzene and the like. What was taken can also be used as a tyrosinase inhibitor.

  Furthermore, if necessary, one or more suitable separation and purification means such as alumina column chromatography, silica gel chromatography, gel filtration chromatography, ion exchange chromatography, hydrophobic chromatography, and high performance liquid chromatography may be combined. A fraction or compound having a tyrosinase inhibitory activity can be taken out and used as a tyrosinase inhibitor. Thereby, the outstanding activity can be exhibited with a small amount of ingestion.

Tyrosinase inhibitory active compound Next, with reference to FIGS. 1-7, the procedure of purification / identification of a tyrosinase inhibitory active compound from Misotake is illustrated.

  Misotake is refluxed with an alcoholic solvent (for example, methanol, ethanol) to obtain an alcohol extract. This extract is suspended in water and dissolved in hexane, methylene chloride, ethyl acetate and 1-butanol, and the fractions are concentrated under reduced pressure to give a hexane transfer part, a methylene chloride transfer part, acetic acid. An ethyl transfer part and a 1-butanol transfer part are obtained. The ethyl acetate insoluble portion having a tyrosinase inhibitory activity (FIG. 2) is fractionated by silica gel column chromatography to obtain active compounds 1 and 2 having a tyrosinase inhibitory activity (FIG. 3). The fractionation by silica gel column chromatography may be repeated several times while changing the polarity of the elution solvent as necessary.

  The active compound was analyzed by various spectral analyses. Coumaroyl serotonin (FIG. 6) and the novel compound 4'-hydroxy-3 ', 5'-dimethoxycinnamoyl serotonin (4'-Hydroxy-3', 5'-dimethoxy- cinnamoyl serotonin) (FIG. 7). The compound has a significantly superior tyrosinase inhibitory activity compared to coumaroyl serotonin (FIG. 5).

  Furthermore, structurally similar compounds were synthesized (FIGS. 8 to 10), and the structure-activity relationship was examined for their tyrosinase inhibitory activity. As a result, tyrosinase inhibition comparable to 4′-hydroxy-3 ′, 5′-dimethoxycinnamoyl serotonin was observed. None had an active effect (FIG. 5).

  The compounds of the present invention have the general formula (I):

(In the formula, R is the same or different and represents an alkyl group.)
Or a salt thereof.

  Examples of the alkyl group represented by R in the general formula (I) include a linear or branched alkyl group having 1 to 10 carbon atoms, and preferably a linear or branched alkyl group having 1 to 6 carbon atoms. And more preferably a linear or branched alkyl group having 1 to 3 carbon atoms. Specifically, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, i-pentyl group, n -Hexyl group, i-hexyl group and the like are exemplified. More preferable R includes a methyl group and an ethyl group, and a methyl group is particularly preferable. That is, 4'-hydroxy-3 ', 5'-dimethoxycinnamoyl serotonin (FIG. 7) is preferable as the compound represented by the general formula (I).

  Examples of the salt of the compound represented by the general formula (I) include salts with inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, carboxylic acids (for example, acetic acid, fumaric acid, maleic acid, succinic acid, etc.), sulfonic acids (for example, And salts with organic acids such as methanesulfonic acid, paratoluenesulfonic acid, benzenesulfonic acid, etc., and salts with alkali metals (for example, sodium, potassium, etc.).

Production Method The compound represented by the general formula (I) can be produced, for example, as follows.

(Wherein R is the same as above)
Specifically, it can be produced by subjecting a compound represented by the general formula (II) or a derivative thereof to a serotonin represented by the general formula (III) or a derivative thereof.

  The derivative of the compound represented by the general formula (II) is, for example, a compound in which a phenolic hydroxyl group is protected with a protecting group (for example, a silyl protecting group, an acyl group, an alkyl group, etc.) or a carboxyl group is activated. And compounds that have formed a compound (for example, a mixed acid anhydride, etc.).

  The derivative of the compound represented by the general formula (III) is, for example, a compound in which an amino group forms a salt (for example, hydrochloride), a phenolic hydroxyl group is a protecting group (for example, a silyl protecting group, acyl Group and the like).

  The compound represented by the general formula (II) or a derivative thereof is usually 1 to 3 mol, preferably 1 to 2 mol, more preferably 1 mol with respect to 1 mol of serotonin or the derivative represented by the general formula (III). 1 to 1.5 mol is used.

  The solvent used may be any solvent that does not adversely affect the condensation reaction. For example, halogen-based hydrocarbon solvents such as methylene chloride and chloroform; ether-based solvents such as diethyl ether, diisopropyl ether, THF, and dioxane; acetone, methyl ethyl ketone, and the like Examples thereof include ketone solvents and the like, or mixed solvents thereof. Methylene chloride is preferred.

  Examples of the condensing agent used in the condensation reaction include EDC, DCC, CDI, and the like. If necessary, an activator such as HOBT; a catalytic amount of DMF; a base such as triethylamine, diisopropylethylamine, pyridine, and DMAP can also be used. The condensing agent is usually used in an amount of 1 to 2 mol per mol of serotonin represented by the general formula (III) or a derivative thereof. The activator is usually used in an amount of 1 to 2 moles per mole of serotonin or a derivative thereof represented by the general formula (III). The base is usually used in an amount of 1 to 2 moles with respect to 1 mole of serotonin or a derivative thereof represented by the general formula (III).

  The reaction temperature is usually about 15 to 30 ° C., and the reaction time is about 8 to 24 hours.

  After completion of the reaction, the compound represented by the general formula (I) is obtained by ordinary post-treatment operations (extraction, washing, concentration, purification, etc.). Reference is made to J. Agri. Food Chem. 2006, 54, 4970-4976.

Whitening Cosmetics The above-mentioned extract from Munetake bamboo and the compound represented by the general formula (I) have an excellent tyrosinase inhibitory action, and are excellent in whitening effects such as an effect of preventing abnormal melanin pigmentation on the epidermis. Therefore, it can be suitably used as a whitening cosmetic.

  In the whitening cosmetic composition of the present invention, the content of the extract from Miso bamboo is about 0.01 to 70% by weight, preferably about 1 to 50% by weight, based on the whole whitening cosmetic.

  In the whitening cosmetic composition of the present invention, the compound (I) or a salt thereof may be used alone or in admixture of any two or more of each. The content of the compound (I) or a salt thereof in the whitening cosmetic of the present invention is about 0.0001 to 50% by weight, preferably about 0.01 to 20% by weight, based on the whole whitening cosmetic. .

  In addition, the whitening cosmetic composition of the present invention can be whitened by further blending one or more selected from the group consisting of other whitening agents, ultraviolet absorbers and keratinization improvers with the above active ingredients. The effect is further improved, and it can be used as a whitening cosmetic not only having an improved melanin suppressing effect but also having a sunburn preventing effect.

  Examples of other whitening agents include allantoin, vitamin E derivatives, glycyrrhizin, ascorbic acid derivatives such as magnesium ascorbate phosphate, kojic acid, arbutin, pantetinic acid derivatives, placenta extract, anti-inflammatory agents, yokuinin, green tea, kakkon Well-known whitening agents such as various herbal medicines and plant extracts such as mulberry white bark, licorice, hornon, aloe, orange peel, chamomile, ganoderma and the like. The blending amount of the whitening agent is preferably 0.0001 to 40% by weight, more preferably 0.01 to 20% by weight, based on the whole whitening cosmetic.

  Examples of the ultraviolet absorber include organic ultraviolet absorbers such as dibenzoylmethane derivatives, cinnamic acid ester derivatives, benzophenone derivatives, and p-aminobenzoic acid derivatives, and zinc white, mica, mica titanium, titanium oxide, and oxidation. Examples include inorganic ultraviolet absorbers such as magnesium and zirconium oxide. The blending amount of the ultraviolet absorber is preferably 0.1 to 20% by weight, more preferably 0.5 to 10% by weight, based on the whole whitening cosmetic.

  Examples of the keratinization improver include sphingosine derivatives and amine derivatives described in JP-A No. 5-194185. The blending amount of the keratinization improving agent is preferably 0.0001 to 40% by weight, more preferably 0.01 to 20% by weight, based on the whole whitening cosmetic.

  In addition, the whitening cosmetic composition of the present invention is blended with optional ingredients in addition to the above-mentioned effective ingredients, the above-mentioned known whitening agent, the above-mentioned UV absorber, and the keratinization improving agent, as long as the effects of the present invention are not impaired. can do. The above optional components are components that are usually blended in known skin external preparations and facial cosmetics, for example, purified water, ethanol, oily ingredients, humectants, thickeners, depending on the dosage form of the whitening cosmetic. Agents, preservatives, emulsifiers, medicinal ingredients, powders, fragrances, emulsion stabilizers, pH adjusters and the like are used.

  Specifically, the oily component includes liquid paraffin, petrolatum, paraffin wax, squalane, beeswax, carnauba wax, olive oil, lanolin, higher alcohol, fatty acid, synthetic ester oil of higher alcohol and fatty acid, silicone oil, fluorine-based oil, etc. Is mentioned.

  Examples of the humectant include sorbitol, xylitol, glycerin, maltitol, propylene glycol, 1,3-propanediol, 1,3-butylene glycol, 1,4-butylene glycol, sodium pyrrolidonecarboxylate, lactic acid, sodium lactate , Polyoxypropylene fatty acid ester, polyethylene glycol and the like.

  Examples of the thickener include water-soluble polymers such as carboxyvinyl polymer, carboxymethylcellulose, polyvinyl alcohol, carrageenan, and gelatin, and electrolytes such as sodium chloride and potassium chloride.

  Examples of the preservative include urea, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, sodium benzoate and the like.

  Examples of the emulsifier include lecithin, hydrogenated lecithin, α-monoalkyl glyceryl ether, polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxy Examples include ethylene glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitol fatty acid ester, and silicone emulsifier.

  Examples of the medicinal component include antihistamines (difedramine hydrochloride, chlorpheniramine maleate, glycyrrhizic acid derivatives, etc.), hormones (estradiol, estrone, ethylestradiol, cortisone, hydrocortisone, prednisolone, etc.) and the like.

  Examples of the powder include talc, sericite, mica, kaolin, silica, bentonite, vermiculite, barium sulfate, bengara, iron oxide, ultramarine and the like.

  Examples of the fragrances include limonene, linanol, citral, β-ionone, benzyl benzoate, indole, eugenol, auranthiol, geraniol, rilal, damascon, benzyl acetate, jasmine lactone, galac solid, and essential oil.

  Examples of the pH adjuster include buffers such as lactic acid-sodium lactate and citric acid-sodium citrate.

  The whitening cosmetic composition of the present invention can be made into various forms by a conventional method, and the form is not particularly limited, but in general, it is a lotion, emulsion, cream, ointment, stick, organic solvent, It is preferable to use a solution such as purified water, a pack, or a gel. That is, the whitening cosmetics of the present invention include whitening cosmetics such as lotions, oil essences, O / W type or W / O type creams, emulsified cosmetics, packs, ointments, whitening foundations, cosmetic emulsions and lotions. , Oily cosmetics, lipsticks, foundations, skin cleansers, hair tonics, hair styling agents, hair nourishing agents, hair restoration agents, bath preparations, shampoos, rinses and the like.

  The whitening cosmetic composition of the present invention can be applied locally to affected areas such as skin irritation caused by ultraviolet rays, spots, freckles, and pigmented areas after sunburn, thereby treating and improving the area to restore normal skin color. In addition, when applied locally in advance, the above symptoms can be prevented.

  Next, the present invention will be specifically described, but the present invention is not limited thereto.

Example 1 (Isolation of a new serotonin compound derived from Miso bamboo)
10 kg of methanol was used as an extraction solvent for 4 kg of Somune bamboo powder, and heated under reflux for 2 hours. Thereafter, filtration was performed, and the methanol extract of Miso bamboo was concentrated under reduced pressure to obtain 140 g of a methanol extract. The obtained methanol extract was transferred to various solvents (hexane, methylene chloride, ethyl acetate, and 1-butanol) to obtain each transferred portion (FIG. 1).

  In order to confirm the tyrosinase inhibitory activity, a tyrosinase inhibitory activity test was carried out for each of the transferred portions. As a test method, each sample was dissolved in DMSO in 140 μL of 0.1 M phosphate buffer (pH 6.8), and 12.5 μL was added. Further, 16 μL of tyrosinase (500 units / ml) and finally 36 μL of 1.5 mM L-tyrosine were added and shaken at 37 ° C. for 25 minutes, and the absorbance was measured at a wavelength of 492 nm.

  The tyrosinase inhibitory activity rate (%) on the vertical axis of each graph was calculated as follows.

・ Control blank: Absorbance of buffer, DMSO and enzyme (tyrosinase) system without substrate (L-tyrosine) ・ Control: Absorbance of substrate (L-tyrosine), buffer, DMSO and enzyme (tyrosinase) system ・ ・・ Enzyme and substrate react to develop color ・ Sample blank: Absorbance of sample, buffer, DMSO and enzyme (tyrosinase) system ・ Check the color of sample itself ・ Sample: Sample, substrate (L-tyrosine), buffer Absorbance of the system of DMSO and enzyme (tyrosinase): confirming the color development of the enzyme and the substrate. The results are shown in FIG. As a result, tyrosinase inhibitory activity was confirmed in the ethyl acetate transfer part. Further, the ethyl acetate transfer part was fractionated by silica gel chromatography (FIG. 3). As a result, it was confirmed that fraction 1 had tyrosinase inhibitory activity (FIG. 4). In order to confirm the compound derived from this tyrosinase inhibitory activity, it was repeatedly purified by silica gel column chromatography to obtain compounds 1 and 2 (FIG. 3).

  Instrumental analysis was performed on isolated compounds 1 and 2. As a result, it became clear that the chemical structural formulas are shown in FIGS. 6 and 7 below. Compound 1 is a known coumaroyl serotonin (Np-coumaroyl serotonin), and compound 2 is a novel compound 4'-hydroxy-3 ', 5'-dimethoxycinnamoyl serotonin (4'-Hydroxy -3', 5 It was confirmed to be '-dimethoxy-cinnamoyl serotonin).

Example 2 (Tyrosinase inhibitory activity of a novel serotonin compound)
Since the novel serotonin derivative compound of compound 2 obtained in Example 1 was confirmed, other serotonin derivatives (compounds 3, 4 and 5) similar in structure were also synthesized (see Example 3). The chemical structural formulas and various instrumental analysis data shown for compounds 3, 4 and 5 are shown in FIGS.

  For compounds 1 to 5, the tyrosinase inhibitory activity test was carried out in the same manner as in Example 1, and the inhibitory activity rate was measured. Compound concentrations were adjusted so that final concentrations were 300 μM, 150 μM, 75 μM, 30 μM, and 15 μM. The result is shown in FIG.

  Arbutin was used as a comparative compound. As a result, as shown in FIG. 5, coumaroyl serotonin, which is compound 1, and feruloyl serotonin, which is synthesized compound 3, showed stronger inhibitory activity than arbutin as tyrosinase inhibitory activity. The newly identified compound 2, namely 4'-hydroxy-3 ', 5'-dimethoxycinnamoyl serotonin, was confirmed to have significantly higher activity than the above two compounds.

  Other synthesized serotonin compounds, compound 4 cinnamoyl serotonin and compound 5, 3 ', 4'-dimethoxycinnamoyl serotonin, have low tyrosinase inhibitory activity. As a result.

  From the above, it was confirmed for the first time that Compound 2 newly confirmed this time is far superior to other serotonin compounds.

Example 3 (Synthesis of serotonin derivatives: compounds 1 to 5)

  J. Agri. Food Chem. 2006, 54, 4970-4976 was used as a reference. Cinnamic acid, serotonin hydrochloride, and HOBT (1-hydroxybenzotriazole) were added to the reaction vessel, and the inside of the reaction vessel was replaced with nitrogen. Then, after adding DMF (dimethylformamide) and dissolving in a nitrogen stream, add methylene chloride, then triethylamine, then EDC (1- [3- (Dimethylamino) propyl] -3-ethylcarbodiimide) to room temperature. And allowed to stir overnight. Table 1 shows the equivalent relationship between the raw materials and the reagents.

  Thereafter, the reaction solution was concentrated under reduced pressure, water was added to suspend it, and extraction was performed with ethyl acetate. The ethyl acetate layer was washed with 5% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over sodium sulfate, and concentrated to obtain a reaction product as a solid.

  As described above, five types of serotonin derivatives including compounds isolated from nature were synthesized. Table 2 shows the yield.

Example 4 (whitening cosmetic)
Using the 4′-hydroxy-3 ′, 5′-dimethoxycinnamoyl serotonin (compound 2) obtained in Example 2 or 3, the whitening cosmetics of the following Production Examples 1 to 3 can be prepared.

Claims (3)

Formula (I):

(In the formula, R is the same or different and represents an alkyl group.)
A tyrosinase inhibitor containing the compound represented by the formula (I) or a salt thereof as an active ingredient (except for the case where the compound represented by the general formula (I) is contained in the extract of Misotake) . The tyrosinase inhibitor according to claim 1, wherein in general formula (I), R is the same or different and is an alkyl group having 1 to 3 carbon atoms. A whitening cosmetic comprising the compound according to claim 1 as an active ingredient.

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