KR101479132B1 - Method for producing kaempferol-glucoside and Use in functional cosmetics of the compound - Google Patents

Abstract

The present invention relates to the use of kaempferol-3-O-glucoside (KOG) and functional cosmetics. More specifically, the present invention relates to a process for producing the compound of the present invention and a method for producing And thus it can be utilized as a material for functional cosmetics and the like.

Description

[0001] The present invention relates to a process for preparing camphor glycosides and to their use as functional cosmetics.

The present invention relates to the use of kaempferol-3-O-glucoside (KOG) and functional cosmetics. More specifically, the present invention relates to a process for producing the compound of the present invention and a method for producing And thus it can be utilized as a material for functional cosmetics and the like.

Human skin color is caused by melanin pigment. Melanin is produced in melanocytes, which are specific dendritic cells found under or between basal cells of the epidermis of the skin (US Patent No. 5,411, 741). Melanin is synthesized by a multistage reaction induced by tyrosinase enzymes (US Pat. No. 5,262,153).

Typical pigmentation is characterized by a uniform, even coloration of the skin. Many people have hyper-melanin deposits or hyperpigmentation spots that can cause pigmentary mutations or abnormal deposits in the skin. This may include hyperpigmentation, phototoxic reactions and other similar small fixed pigments after inflammation caused by unwanted freckles or aging spots, dark spots such as liver, spots, brown or senile spots, albumin, sunlight pigmentation, scratches, burns, Sexual lesions can be caused. It is often desirable to whiten these areas in the skin or to trim the pigmented areas non-uniformly.

People may want to increase the clarity and clarity of skin texture and reduce the overall level of skin pigmentation. In any case, hyperpigmentation is generally considered undesirable for cosmetics, and people often want skin whitening.

On the other hand, as the concern about the protection of experimental animals has increased, the movement to exclude animal experiments from the safety test of cosmetics has been gradually increasing. However, since this can be used when a natural material derived from a natural material has been used for various purposes, Interest in discovering functional cosmetic materials is gradually increasing.

3-O-glucoside (kaempferol-3-O-glucoside, KOG), also known as astragalin, is known to be contained in a black currant called black cranberry, black currant, Is known to be contained in Astragalus membranaceus (Biomed. Mater. Eng. 22: 113 (2012). Hwanggi has been used as a kind of herb used for lethargy, depression, hemostasis, and diarrhea. KOG is a type of polyphenol that is known to exhibit a variety of biological functions including immune-related efficacy, but it is rarely utilized because it is difficult to obtain large quantities [Biochem. Biophys. Res. Commun. 419: 256 (2012)).

Korean Patent Publication No. 10-2012-0068111 relates to an extract of cedar essential oil having whitening and antioxidative activity and is characterized in that a tyrosinase inhibitory activity and a DPPH (1,1-diphenyl-2-picryl-hydrazyl) radical The present invention relates to a cedar essential oil extract which is extracted through steam distillation with superoxide dismutase (SOD) -activating activity and a whitening and antioxidative effect containing borneol and nezukol components having high whitening and antioxidant activity. .

SUMMARY OF THE INVENTION The present invention has been made in view of the above needs, and an object of the present invention is to provide a process for mass production of novel kaempferol-3-O-glucoside (KOG).

It is another object of the present invention to provide novel functional cosmetic and / or pharmaceutical materials.

In order to achieve the above object, the present invention provides a cosmetic composition comprising a compound of the following formula (1) as an active ingredient.

[Chemical Formula 1]

In one embodiment of the present invention, the composition preferably has a whitening effect and preferably inhibits intracellular melanin production, but is not limited thereto.

The present invention also provides a pharmaceutical composition comprising a compound of the following formula (1) as an active ingredient.

[Chemical Formula 1]

The present invention also provides a food composition having a whitening-improving effect comprising a compound of the following formula (1) as an active ingredient.

[Chemical Formula 1]

The present invention also relates to a process for preparing a methoxymethyl 4- (methoxymethoxy) benzoate by adding potassium carbonate and methoxymethyl chloride to a solution obtained by dissolving a-1) 4-hydroxybenzoic acid, b) (Methoxymethoxy) benzoate is dissolved in tetrahydrofuran, followed by the addition of lithium hydroxide to synthesize 4- (methoxymethoxy) benzoic acid, a-2) dissolving the beta-D-glucose pentaacetate in dichloromethane A-3) A solution prepared by dissolving quercetin in N, N-dimethylformamide was added potassium carbonate (DMSO) to a solution of tetraacetylglucose The reaction mixture was cooled and concentrated under reduced pressure. The resulting residue was recrystallized from dichloromethane / ethyl acetate to give 3,5,7-tris (benzyloxy) -2- (3,4- Bis (benzyloxy) phenyl) -4H-chromen-4- 3-hydroxyphenyl) ethanone is synthesized by adding diethylene glycol and potassium hydroxide to c) 2- (benzyloxy) -1- (2,4-bis (benzyloxy) (Benzyloxy) -1- (2,4-bis (benzyloxy) -6-hydroxyphenyl) ethanone synthesized in Example 1 and 4- (methoxymethoxy) benzoic acid synthesized in b) (Benzyloxy) -2- (3-dimethylaminopropyl) carbodiimide (EDC) was obtained by adding 4-dimethylaminopyridine and 1-ethyl- Bis (benzyloxy) -2- (2- (benzyloxy) acetyl) phenyl 4- (methoxymethoxy) benzoate; d) Acetyl) phenyl 4- (methoxymethoxy) benzoate was dissolved in toluene, potassium carbonate and tetrabutylammonium bromide were added to the mixture to give 3,7-bis (benzyloxy) -4 '(methoxymethoxy) E) dissolving 3,7-bis (benzyloxy) -4 '(methoxymethylphenyl) propane obtained in step d) Propoxy) -camphorol was dissolved in methanol and tetrahydrofuran, palladium / charcoal was added thereto, and the mixture was concentrated under reduced pressure. The concentrate was dissolved in acetone, and potassium carbonate and methoxymethyl chloride were added thereto to obtain 3,4'-bis (Methoxymethoxy) -camperol, f) the 3,4'-bis (methoxymethoxy) -camphorol obtained in step e) is dissolved in chloroform and water, and calcium carbonate is added thereto. D-brominated tetraacetylglucose compound and Aliquat 336 obtained in the above a-2) were added to the mixture, and the mixture was refined. To the solution obtained by dissolving the compound in dichloromethane was added trifluoroacetic acid, and the mixture was stirred 3-O-beta-acetylated-glucoside to obtain camphorol-3-O-beta-acetylated-glucoside obtained in step f) After dissolving in methanol, the reaction To including the step of concentration under reduced pressure the compound provides a process for the preparation of compounds of formula (I).

[Chemical Formula 1]

Hereinafter, the present invention will be described.

The present inventors have provided a method for mass production of kaempferol-3-O-glucoside (KOG), and conducted a whitening efficacy test of this material to find out that it is possible to utilize it as a functional cosmetic material , Thereby completing the present invention.

The present invention solves the problems of the prior art by providing compositions that can be used for skin whitening and methods of use thereof. For example, the composition of the present invention may be a compound of the above formula (I), a substituent, a derivative or an equivalent thereof, all of which are considered to be part of the present invention. In addition, the compositions of the present invention may include additional components and compounds discussed and inserted herein. In addition, any combination of the above compounds or components should be regarded as useful in the present invention.

In particular aspects, the compositions of the present invention may be prepared in cosmetic formulations.

In certain embodiments, the composition may be chemically compatible. The composition may also comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or more pHs. The composition may also be included in a cosmetic vehicle. Non-limiting examples of vehicles for cosmetics may include emulsions, creams, lotions, solutions, anhydrous substrates, gels and ointments, and other vehicles as discussed herein and known to those skilled in the art. In a particular aspect, the cosmetic vehicle is an oil-in-water emulsion, a water-in-oil emulsion, an aqueous solution, or a water-alcohol solution. In a non-limiting aspect, the anhydrous substrate is a lipstick or powder. In another embodiment, the composition can be included in cosmetics. Non-limiting examples of cosmetics include, but are not limited to, skin whitening products, anti-aging products, moisturizing products, foundations, masks, lotions, skin softeners, cleansers, creams And other products which are incorporated herein by reference.

In certain embodiments, the compositions of the present invention are administered once, twice, three times, four times, five times, six times, seven times, eight times, nine times, ten times, eleven times, Times, 14 times, 15 times, 16 times, 17 times, or more. The composition of the present invention may be used in the form of a prescription. For example, the prescription may include applying various products to the skin of a person in the morning or evening, or both morning and evening. In another aspect, the various products can be applied at various intervals at any time during the day or evening. The spacing may vary depending on the intended effect of the given person or product. For example, in a non-limiting embodiment, the formulation may comprise the application of a cleanser, softener, lotion, sunscreen and / or foundation in the morning, and any or all of these products may be present in the compositions of the present invention . Other non-limiting examples of formulations may include the application of a cleanser, mask, softener, lotion and / or night cream in the evening. It is believed that any, or some or all, of these products comprise the compositions of the present invention. In a particular aspect, the prescription may include a combination of morning and evening prescriptions. Any form of prescription may be used with the present invention. The prescription may vary depending on the specific needs or purposes of the person using the product. The length of prescription time may vary. For example, the prescription may be performed for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 days or more. In another non-limiting example, the length of the prescription time is 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 100, 200 weeks or more.

The composition of the present invention may be manufactured as a leave-on composition, a cleaning composition, or a cleansing composition in a non-limiting sense. The composition is prepared to have a Sun Protection Factor (SPF) of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, . The composition may be made, for example, in cosmetics.

Non-limiting examples of cosmetics include skin softener, day or night lotion, day or night cream, foundation, cleanser, mask or sunscreen. However, it is contemplated that the compositions of the present invention may be incorporated into any form of cosmetics discussed herein or known to those skilled in the art.

It is contemplated that any aspect discussed herein may be practiced in connection with any method or composition of the present invention and vice versa. In addition, the compositions of the present invention may be used to achieve the methods of the present invention.

The terms "inhibition", "reduction" or "prevention" or any variation of these terms as used in the claims and / or the specification include measurable reduction or complete inhibition to achieve the desired result.

The singular terms used in conjunction with the word "comprising" in the claims and / or the specification may mean "one species ", but" at least one species ", "at least one species & In the same way.

In the claims, the term "or" means "and / or ", unless the term specifically refers to either one or both of them, but the term " .

As used herein and in the claims, the terms "comprising" (and any form of comprising such as "includes"), "having" (and any form of having, such as "having" The term " comprising ") is intended to be inclusive or non-limiting and does not exclude additional elements or method steps not quoted.

The chemical structures and modifications or derivatives of the compounds described herein are believed to be useful in the methods and compositions of the present invention. The derivatives can be prepared and the properties of these derivatives can be analyzed for their desired properties by any method known to those skilled in the art.

In a particular aspect, "derivative" means a chemically modified compound, inhibitor or stimulant that still retains the desired properties prior to chemical modification. Such derivatives may add, remove or substitute one or more chemical moieties on the parent molecule. Non-limiting examples of modifications that can be made in the compounds and structures described herein include lower alkanes such as methyl, ethyl, propyl, or substituted lower alkanes such as hydroxymethyl or aminomethyl groups; A carboxyl group and a carbonyl group; Hydroxyl; Nitro, amino, amide and azo groups; Addition or removal of a sulfonate, sulfonate, sulfonate, sulfhydryl, sulfonyl, sulfoxide, phosphate, phosphono, phosphoryl group and halide substituent. Additional modifications may include addition or deletion of one or more atoms of the atomic backbone.

Known compounds and extracts of the specific compounds discussed herein and known equivalents and active ingredients for the active ingredients can be used in the compositions and methods of the present invention. Equivalents can be used as substitutes for certain compounds, extracts and active ingredients. Equivalents may also be used to add to the methods and compositions of the present invention. A person of ordinary skill in the art will be able to recognize and identify known and unknown equivalents that are acceptable to the particular compound, extract, and active ingredient without undue experimentation.

The compositions of the present invention are effective for all types of cosmetic vehicles. Non-limiting examples of suitable cosmetic vehicles include emulsions, creams, lotions, solutions (aqueous and alcoholic solutions), anhydrous substrates (such as lipsticks and powders), gels and ointments or other conventional methods known to those skilled in the art Formulations and other suitable vehicles will be apparent to those skilled in the art and are suitable for use in the present invention.

In a particular aspect, the cosmetic vehicle is selected from an oil-in-water emulsion, a water-alcohol solution, or an encapsulated bead in a water-free system. Such emulsions and their compositions and methods of preparation for oil-in-water emulsions are well known in the art. However, it is important that the concentrations and combinations of compounds and extracts are chosen such that the combination is chemically compatible and does not form complexes that precipitate from the final product.

The compositions of the present invention include, but are not limited to, moisturizing creams, cream and lotions, softeners, lotions, gels, ointments, foundations, night creams, lipsticks, cleansers, toners, masks, Which may be used in many cosmetics. In addition, cosmetics may be formulated as rib-on or rinse-off products.

The compositions of the present invention are most preferably used in skin whitening products for the face and other body parts.

The composition of the present invention may be used in combination with, for example, an acute or chronic moisturizing agent (for example, a wetting agent, a sealant, and an agent that affects the natural moisturizing mechanism of the skin), an antioxidant, a UVB and / , Emollients, anti-irritants, vitamins, trace metals, antibacterial agents, vegetable extracts, fragrances, and / or other beneficial agents and compounds such as dyes and color components.

1. Moisturizing agent

Nonlimiting examples of humectants that may be used in the compositions of the present invention include, but are not limited to, amino acids, chondroitin sulfate, diglycerin, erythritol, fructose, glucose, glycerin, glycerol polymers, glycols, 1,2,6- hexanetriol, PEG-15 butanediol, polyglyceryl sorbitol, salts of pyrrolidonecarboxylic acid, potassium PCA, propylene glycol, propylene glycol, propylene glycol, propylene glycol, , Sodium glucuronate, sodium PCA, sorbitol, sucrose, trehalose, urea, and xylitol.

Other examples include acetylated lanolin, acetylated lanolin alcohol, acrylate / C10-30 alkyl acrylate crosspolymer, acrylate copolymer, alanine, seaweed extract, aloe barbadensis, aloe verbadensis extract, aloe Arbutin, arbutin, arginine, arginine, arginine, arginine, arginine, arginine, arginine, arginine, aspartate, Extracts, ascorbic acid, ascorbyl palmitate, aspartic acid, persea gratissima oil, barium sulphate, barrier spindle feed, butyl alcohol, beeswax, behenyl alcohol, beta-sitosterol, BHT, Betula (betula alba) bark extract, dill (borago officinalis) extract, 2- Dihydro-2-nitropropane-1, 3-diol, Butcher broth (ruscus aculeatus) extract, butylene glycol, calendula officinalis extract, calendula officinalis Oil, canardella (euphorbia cerifera) wax, canola oil, caprylic / capric triglyceride, cardamone (elettaria cardamomum) oil, carnauba (copernicia (Copernicia cerifera) wax, carrageenan (chondrus crispus), carrot (daucus carota sativa) oil, castor oil (ricinus communis) oil, Ceteth-20, Ceteth-24, Cetyl Acetate, Cetyl Octanoate, Cetyl Palmitate, Chamomile (Catechol) Anthemis nobilis) O , Cholesterol ester, cholesterol hydroxystearate, citric acid, clary (salvia sclarea) oil, cocoa (theobroma cacao) butter, coco-caprylate / caprate , Coconut (cocos nucifera) oil, collagen, collagen amino acid, corn (zea mays) oil, fatty acid, decyl oleate, dextrin, diazolidinyl urea, dimethicone copolyol, dimethiconol , Dodecyl adipate, dioctyl succinate, dipentaerythritol hexacaprylate / hexacaprate, DMDM hydantoin, DNA, erythritol, ethoxydiglycol, ethyl linoleate, eucalyptus glow blues oil, Glutamate, glutamic acid, glutamic acid, glutamic acid, glutamic acid, glutamic acid, glutamic acid, Glyceryl distearate, glyceryl hydroxystearate, glyceryl laurate, glyceryl linoleate, glyceryl myristate, glyceryl oleate, glyceryl stearate, glycerol, glycerol, (Stearyl stearate SE, glycine, glycol stearate, glycol stearate SE, glycosaminoglycan, grape (vitis vinifera) seed oil, hazel (corylus americana) (Corylus avellana) nut oil, hexylene glycol, honey, hyaluronic acid, mixed safflower (carthamus tinctorius) oil, hydrogenated castor oil, hydrogenated coco-glycerides, hydrogenated coconut oil , Hydrogenated lanolin, hydrogenated lecithin, hydrogenated palm glyceride, hydrogenated palm kernel oil, hydrogenated soybean oil, hydrogenated tallow glyceride, hydrogen Vegetable oil, hydrolyzed collagen, hydrolyzed elastin, hydrolyzed glycosaminoglycan, hydrolyzed keratin, hydrolyzed soy protein, hydroxylated lanolin, hydroxyproline, imidazolidinyl urea, iodopropynyl butylcarbamate , Isocetyl stearate, isocetyl stearoyl stearate, isodecyl oleate, isopropyl isostearate, isopropyl lanolate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isostearamide DEA, Isostearic acid, isostearyl lactate, isostearyl neopentanonate, jasmine (jasminum officinale) oil, jojoba (buxus chinensis) oil, kelp, (Aleurites moluccana) nut oil, lactamide MEA, lanes-16, lanes-10 acetate, (Citrus medica limonum) oil, linoleic acid, linolenic acid, macadamia < RTI ID = 0.0 > terr < / RTI > oil, lanolin, lanolin, lanolin, lanolin, lanolin wax, lavender (lavandula angustifolia) But are not limited to, petroleum nano oil, magnesium stearate, magnesium sulfate, maltitol, martricaria (chamomilla recutita) oil, methylglucossequistate, methylsilanol PCA, microcrystalline wax, But are not limited to, oils, mortierella oil, myristyl lactate, myristyl myristate, myristyl propionate, neopentyl glycol dicaprylate / dicaprate, octyldodecanol, octyldodecyl myristate, octyldodecyl Stearoyl stearate, octyl hydroxystearate, octyl palmitate, octyl salicylate, octyl stearate, (Olea europaea) oil, orange (citrus aurantium dulcis) oil, palm (elaeis guineensis) oil, palmitic acid, pantethine Panthenol (Arachis hypogaea) oil, PEG-8 C12-18 ester, PEG-15 (Phenol), Panthenol, Panthenol, Panthenyl ethyl ether, Paraffin, PCA, Peach (prunus persica) PEG-40 hydrogenated castor oil, PEG-40 glyceryl isostearate, PEG-5 glyceryl stearate, PEG-30 glyceryl stearate, PEG-7 hydrogenated castor oil, PEG- PEG-20 soybean sterol, PEG-10 soybean sterol, PEG-2 stearate, PEG-8 stearate, PEG-20 stearate, PEG-32 stearate, PEG-40 stearate, PEG-50 stearate PEG-100 stearate, PEG-150 stearate, pentadecaractone, peppermint (mentha piperita) oil, petrolatum, phospholipid, polyamino sugar condensate, polyglyceryl-3 diisostearate Polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, polyvinylpyrrolidone, Propylene glycol stearate SE, PVP, pyridoxine dipalmitate, quaternium-diallyl phthalate, propylene glycol dicaprylate / dicaprate, propylene glycol dioctanoate, propylene glycol dipelarnonate, propylene glycol laurate, propylene glycol stearate, 15, quaternium-18 hectorite, quaternium-22, retinol, retinyl palmitate, rice (oryza sativa) bran oil, R (Rosmarinus officinalis) oil, rose oil, safflower (carthamus tinctorius) oil, sage (salvia officinalis) oil, salicylic acid , Sesame oil (sesamum indicum) oil, shea butter (butyrospermum parkii), silk powder, sodium chondroitin (sodium chloride) Sodium stearate, soluble collagen, sorbic acid, sorbitan laurate, sorbitan palmitate, sorbitan palmitate, sorbitan palmitate, sorbitan palmitate, sorbitan palmitate, sorbitan palmitate, Sorbitol, soybean (glycine soja) oil, safflingfeed, squalane, squalane, stearamide MEA- Stearyl stearate, sunflower (helianthus annuus), stearic acid, stearic acid, stearic acid, stearic acid, stearoxydimethicone, stearoxytrimethylsilane, stearyl alcohol, stearyl glycyrrhetinate, stearyl heptanoate, Seed oil, sweet almond (prunus amygdalus dulcis) oil, synthetic beeswax, tocopherol, tocopheryl acetate, tocopheryl linoleate, tribehenin, tridecyl neopentanoate, tridecyl stearate Water, wax, wheat (triticum vulgare) germ oil and ylang ylang (cananga odorata) oil. The term " oil "

2. Antioxidant

Non-limiting examples of antioxidants that may be used in the compositions of the present invention include, but are not limited to, acetylcysteine, ascorbic acid, ascorbic acid polypeptides, ascorbyl dipalmitate, ascorbyl methylsilanol pectinate, ascorbyl palmitate, But are not limited to, phthalic anhydride, phthalic anhydride, phthalic anhydride, phthalic anhydride, phthalic anhydride, bisstearate, BHA, BHT, tertiary-butyl hydroquinone, cysteine, cysteine HCl, diamylhydroquinone, Diethylacrylate, erythorbic acid, esters of ascorbic acid, ethyl ferulate, ferulic acid, gallic acid ester, hydroxycarboxylic acid ester, hydroxycarboxylic acid ester, Quinone, isooctyl thioglycolate, kojic acid, magnesium ascorbate, magnesium ascorbyl phosphate, methylsilanolates Natural vegetable antioxidants such as Lebite, green tea or grape seed extract, nordihydroguaiaretic acid, octyl gallate, phenyl thioglycolic acid, potassium ascorbyl tocopheryl phosphate, potassium sulfite, propyl gallate, quinone, Sodium thioglycolate, sorbityl furfural, thiodiglycol, thiodiglycolamide, thiodiglycolamide, thiodiglycolamide, thiodiglycolamide, thiodiglycolamide, thiodiglycolamide, thiodiglycolamide, Tocopherol-10, tocopherol-12, tocopherol-18, tocopherol-50, tocopherol, tocopherollan, tocopheryl acetate, tocopherol acetate, thioglycolic acid, thioacetic acid, Tocopheryl linoleate, tocopheryl nicotinate, tocopheryl succinate and tris (nonylphenyl) phosphite.

3. Compounds having ultraviolet light absorption properties

Non-limiting examples of compounds having ultraviolet light absorption properties that can be used with the compounds of the present invention include benzophenone, benzophenone-1, benzophenone-2, benzophenone-3, benzophenone- 6, benzophenone-7, benzophenone-8, benzophenone-9, benzophenone-10, benzophenone-11, benzophenone-12, benzyl salicylate, butyl PABA, cinnamate ester, Methoxy cinnamate, diisopropylmethyl cinnamate, ethyl dihydroxypropyl PABA, ethyldiisopropyl cinnamate, ethyl methoxy cinnamate, ethyl PABA, ethyl urocanate, glyceryl octanoate dimethoxy cinnamate, Glyceryl PABA, glycol salicylate, homosalate, isoamyl p-methoxy cinnamate, PABA, PABA ester, Parsol 1789 and isopropylbenzyl salicylate.

4. Constituent Ingredients

In another non-limiting aspect, the compositions of the present invention may comprise constituent components. In certain aspects, the structuring component aids in providing rheological properties to the composition to contribute to the stability of the composition. In another aspect, the constituting component may act as an emulsifying agent or a surfactant. Non-limiting examples of constituent components include stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, palmitic acid, polyethylene of stearyl alcohol having an average of from about 1 to about 21 ethylene oxide units Glycol ethers, polyethylene glycol ethers of cetyl alcohol having an average of from about 1 to about 5 ethylene oxide units, and mixtures thereof.

5. Emulsifier

In certain preferred aspects of the present invention, the composition does not comprise an emulsifier. However, in another aspect, the composition may comprise one or more emulsifiers. Emulsifiers can reduce the interfacial tension between the phases and improve the formulation and stability of the emulsion. Emulsifiers can be non-ionic, cationic, anionic, and amphoteric emulsifiers (McCutcheon's (1986), U.S. Patents 5,011,681, 4,421,769, 3,755,560). Non-limiting examples include esters of glycerine, esters of propylene glycol, fatty acid esters of polyethylene glycol, fatty acid esters of polypropylene glycol, esters of sorbitol, esters of sorbitan anhydride, carboxylic acid copolymers, esters and ethers of glucose, ethoxylated ethers, Fatty acid amides, acyl lactylates, soaps, TEA stearate, DEA ole-3 phosphate, polyethylene glycol 20 sorbitan monolaurate (polysorbate 20), polyethylene (polyoxyethylene sorbitan fatty acid esters) Ceteth-10, polysorbate 80, cetyl phosphate, potassium cetyl-20, stearate-21, cetearase-20, PPG-2 methyl glucose ether distearate, Phosphate, diethanolamine cetyl phosphate, poly Le polysorbate 60, glyceryl stearate, PEG-100 stearate, are included, and mixtures thereof.

6. Silicon-containing compound

In a non-limiting aspect, the silicon-containing compound includes an element in the polymer product class having a side chain group in which the molecular skeleton has a silicon atom and an oxygen atom alternately bonded to a silicon atom. Silicon can be synthesized in a wide variety of materials by varying the -Si-O-chain length, side-chain groups, and cross-linking. Their roughness can vary from liquid to gel to solid.

Silicon-containing compounds that may be used in the present invention include those described herein, or those known to those skilled in the art. Non-limiting examples include silicone oils (e.g., volatile and non-volatile oils), gels, and solids. In a preferred aspect, the silicon containing compound comprises a silicone oil such as a polyorganosiloxane. Nonlimiting examples of polyorganosiloxanes include, but are not limited to, dimethicone, cyclomethicone, polysilicon-11, phenyl trimethicone, trimethylsilylamodimethicone, stearoxytrimethylsilane, And mixtures of these and other organosiloxane materials in any desired proportions to achieve the desired roughness and coating properties. A "volatile silicone oil" includes a silicone oil having a low evaporation heat of less than about 50 cal per gram of silicone oil. Non-limiting examples of volatile silicone oils include cyclomethicone, such as Dow Corning 344 Fluid, Dow Corning 345 Fluid, Dow Corning 244 Fluid, and Dow Corning 245 Fluid, volatile silicone 7207 from Union Carbide Corp., Danbury, Conn. ; Low dimethicone, i.e. dimethicone having a viscosity of about 50 cst or less (e.g. dimethicone such as Dow Corning 200-0.5 cst fluoride). Dow Corning Fluid is available from Dow Corning Corporation (Midland, Mich.). Cyclomethicone and dimethicone are each described as a mixture of cyclic dimethylpolysiloxane compounds and fully methylated linear siloxane polymers terminated in trimethylsiloxane units, respectively, in the CTFA Cosmetic Ingredient Dictionary, Third Edition (cited hereinabove). Other non-limiting volatile silicone oils that may be used in the present invention include General Electric Co., Silicone Products Div., Waterford, N.Y. And those available from SWS Silicones Div., Stauffer Chemical Co., Adrian, Michigan.

7. Essential Oils

Essential oils include oils obtained from herbs, flowers, trees and other plants. Such oils are typically present as small droplets between the cells of the plant and can be formed by various methods known to those skilled in the art, such as steam distillation, freezing (i.e., extraction with fats), burning, solvent extraction, or mechanical compression . This type of oil tends to evaporate upon exposure to air (i.e., volatile oil). As a result, many essential oils are colorless, but they can oxidize over time and become thicker. Essential oils are insoluble in water and can be dissolved in alcohol, ether, non-volatile oils (vegetable), and other organic solvents. Typical physical properties found in essential oils include various boiling points ranging from about 160 to 240 캜 and densities ranging from about 0.759 to about 1.096.

Essential oils are typically named from plants where the oil is found. For example, rose oil or peppermint oil is obtained from a rose or peppermint plant, respectively. Non-limiting examples of essential oils that may be used in the present invention include sesame oil, macadamia nut oil, tea tree oil, evening primrose oil, Spanish sage oil, Spanish rosemary oil, coriander oil, thyme oil, pimentoberry oil, rose oil Sardine oil, clary sage oil, clove oil, cypress oil, eucalyptus oil, fennel oil, sea fennel oil, frankincense oil, geranium oil, sesame oil, bergam oil, bergam oil, rosemary oil, cedar oil, chamomile oil, , Ginger oil, grapefruit oil, jasmine oil, juniper oil, lavender oil, lemon oil, lemon grass oil, lime oil, mandarin oil, myrrh oil, neroli oil, orange oil, Grain Oil, Pine Oil, Rose Otto Oil, Rosemary Oil, Sandalwood Oil, Spearmint O , Spikenard oil, vetiver oil, wintergreen oil, or ylang ylang are included. Other essential oils known to those skilled in the art are also considered useful in the present invention.

8. Thickener

Thickening agents, including thickeners or gelling agents, include materials that can increase the viscosity of the composition. Preferred thickening agents include those that can increase the viscosity of the composition without substantially altering the effectiveness of the active ingredient in the composition. Thickening agents can also increase the stability of the compositions of the present invention. In certain aspects of the invention, preferred thickeners include hydrogenated polyisobutene or trihydroxystearine, or mixtures of the two.

Non-limiting examples of other thickeners that may be used in the present invention include carboxylic acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers, polysaccharides and gums. Examples of carboxylic acid polymers include acrylic acid, substituted acrylic acid, and crosslinking compounds containing one or more monomers derived from salts and esters of substituted acrylic acid with acrylic acid, wherein the crosslinking agent is a copolymer of two or more carbon- (US Pat. Nos. 5,087,445, 4,509,949, 2,798,053, CTFA International Cosmetic Ingredient Dictionary, Fourth edition, 1991, pp 12 and 80). Examples of commercially available carboxylic acid polymers include carbomers (e.g., Carbopol (TM) 900 Siez, B.F. Goodrich) which are homopolymers of acrylic acid crosslinked with allyl ether of sucrose or pentaerythritol.

Non-limiting examples of crosslinked polyacrylate polymers include cationic and nonionic polymers. Examples thereof are described in the literature (see U.S. Patent Nos. 5,100,660, 4,849,484, 4,835,206, 4,628,078, 4,599,379).

Non-limiting examples of polyacrylamide polymers (including non-ionic polyacrylamide polymers including substituted branched or unbranched polymers) include polyacrylamides, isoparaffins and laureth-7, acrylamides and substituted acrylamides and acrylic acid And multi-block copolymers with substituted acrylic acid.

Non-limiting examples of polysaccharides include cellulose, carboxymethylhydroxyethylcellulose, cellulose acetate propionate carboxylate, hydroxyethylcellulose, hydroxyethylethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylhydroxy Ethylcellulose, microcrystalline cellulose, sodium cellulose sulfate, and mixtures thereof. Other examples are hydroxyalkylation (preferably hydroxyethylated or hydroxypropylated) of the hydroxy group of the cellulosic polymer to form a hydroxyalkylated cellulose, followed by ether linkage to a C10-C30 straight chain or branched alkyl group Further modified alkyl substituted cellulose. Typically these polymers are ethers of C10-C30 straight chain or branched chain alcohols and hydroxyalkylcelluloses. Other useful polysaccharides include (1-3) scrooglucan containing a linear chain with every 3 units of linked glucose units and (1-6) linked glucose.

Non-limiting examples of gums that may be used in the present invention include acacia, agar, algin, alginic acid, ammonium alginate, amylopectin, calcium alginate, calcium carrageenan, carnitine, carrageenan, dextrin, gelatin, gellan gum, guar gum, Propyl trimonium chloride, hectorite, hyalurophosphoric acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar, karaya gum, kelp, locust bean gum, natto gum, potassium alginate, potassium carrageenan, Sodium carboxymethyldextran, sodium carrageenan, tragacanth gum, xanthan gum, and mixtures thereof.

9. Additional compounds and formulations

Non-limiting examples of additional compounds and formulations that may be used in the compositions of the present invention include additional skin lightening agents (e.g., kojic acid, hydroquinone, retinoids and derivatives thereof) and other known skin whitening ingredients, (Eg steroids and non-steroidal anti-inflammatory agents), vegetable extracts (eg, aloe vera), antioxidants (such as alginic acid and fatty acids), vitamins such as D, E, A, K and C; trace metals such as zinc, calcium and selenium; D & C Blue No. 4, D & C Green No. 5, D & C Orange No. 4, D & C Red No. 17, D & C Red No. 33, etc.), dyes and color components (E.g., BHA), softeners (i.e., organic esters, fatty acids, lanolin and derivatives thereof, vegetable and animal oils, such as D & C Violet No. 2, D & C Yellow No. 10, D & C Yellow No. 11 and DEA-cetyl phosphate) Oils and fats, and di- and triglycerides), antimicrobial agents : It includes triclosan and ethanol), and fragrances (natural and artificial flavors).

It is possible to mass-produce kaempferol-3-O-glucoside (KOG) of the present invention, and it can be usefully used as a material for functional cosmetics or the like based on the test result of the whitening effect of the compound.

1 shows the synthesis of 4- (methoxymethoxy) benzoic acid with methoxymethyl 4- (methoxymethoxy) benzoate, an intermediate of kaempferol-3-O-glucoside Way. Herein, Compound 1 represents 4-hydroxybenzoic acid, Compound 2 represents methoxymethyl 4- (methoxymethoxy) benzoate, and Compound 3 represents 4- (methoxymethoxy) benzoic acid.
2 is a method for synthesizing beta-D-glucose pentaacetate and beta-D-bromo tetraacetylglucose, which are intermediates of kaempferol-3-O-glucoside (KOG). Here, the compound 4 represents beta-D-glucose pentaacetate and the compound 5 represents beta-D-bromacetate tetraacetyl glucose.
3 is a method for synthesizing kaempferol-3-O-glucoside (KOG). Compound 7 is 2- (benzyloxy) -1- (2,4-bis (benzyloxy) -6-hydroxyphenyl) ethanone, compound 8 is 3,5-bis (benzyloxy) (Methoxymethoxy) benzoate, compound 9 is 3,7-bis (benzyloxy) -4 '(methoxymethoxy) -campearol, compound Compound 10 is camptol-3-O-beta-acetylated-glucoside, Compound 12 is camellol-3-O-glucoside kaempferol-3-O-glucoside, KOG).
FIG. 4 is a graph showing the inhibitory effect of kaempferol-3-O-glucoside (KOG) on intracellular melanin formation. Here, Que represents quercetin, QOG represents quercetin-3-O-glucoside, kaem represents camperol, KOG represents camperol-3-O-glucoside, MSH represents melanocyte-stimulating hormones, and a represents a medium containing no MSH , and b represents the result of the experiment with the medium containing MSH.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these examples are for illustrative purposes only and that the scope of the present invention is not construed as being limited by these examples.

Example  One. Campulol -3-O- Glucoside  ( kaempferol -3-O- glucoside , KOG ) Mass production method

Synthesis of methoxymethyl 4- (methoxymethoxy) benzoate (2):

After the 4-hydroxide benzoic acid (1) (3g, 21.7 mmol ) in solution in acetone (30 mL) was added potassium carbonate (15 g, 108.6 mmol) and methoxymethyl chloride (8.3 mL, 108.6 mmol), 80 o C at reflux for 6 hours (Fig. 1). The residue was purified by column chromatography on silica gel column (8: 1 = hexane: acetic acid ethyl ester) to give methoxymethyl 4- (methoxyphenol) as a pale yellow oil. Benzoate (2) can be obtained. (4.8 g, 21.2 mmol, 97.8% yield): The nuclear magnetic resonance spectroscopy was carried out using Bruker NMR (400 MHz). ^{1 H NMR (400 MHz, Acetone} -d 6) δ 8.03 (d, J = 8.9 Hz, 2H), 7.13 (d, J = 8.9 Hz, 2H), 5.44 (s, 2H), 5.30 (s, 2H) , 3.50 (s, 3H), 3.45 (s, 3H).

Synthesis of 4- (methoxymethoxy) benzoic acid (3):

After dissolving methoxymethyl 4- (methoxymethoxy) benzoate (2.8 g, 21.2 mmol) in tetrahydrofuran (20 mL), lithium hydroxide (2.0 g, 84.8 mmol, ), And the mixture is refluxed at 40 ^° C for 6 hours. After cooling the reaction mixture to 0 ^o C, by the addition of 2N aqueous hydrochloric acid solution to be acidic condition (pH 3). At this time, the resulting white solid is filtered with filter paper to give 4- (methoxymethoxy) benzoic acid (3). (3.5 g, 19.2 mmol, 90.1% yield): ¹ H NMR (400 MHz, Acetone-d ₆ )? 7.99 (d, J = 8.8 Hz, 2H), 7.11 (s, 2 H), 3.45 (s, 3 H).

Synthesis of beta-D-brominated tetraacetyl glucose (5):

(3.9 g, 10 mmol) was dissolved in dichloromethane (15 mL), followed by addition of bromic acid (HBr) (2.6 mL, 45 mmol) and stirring at room temperature for 4 hours [ 2]. To this mixture was added an aqueous solution of sodium hydrogencarbonate (20 mL) and extracted three times with dichloromethane (60 mL). Magnesium sulfate (MgSO ₄ ) was added to the organic layer to remove residual water, I will. The mixture was concentrated under reduced pressure, and the obtained concentrate was purified by silica gel column chromatography (4: 1 = hexane: acetic acid ethyl ester) to give Compound 5 in the form of a white solid. (3.84 g, 9.3 mmol, yield ^{93%): 1 H NMR (} 400 MHz, Acetone) δ (ppm) 6.28 (d, J = 3.7Hz, 1H), 5.47 (t, J = 10.0 Hz, 1H), 5.14 (t, J = 2.0 Hz, 1H), 5.04 (q, J = 3.7 Hz, 1H), 4.20-4.26 (m, 2H), 4.05-4.09 (m, s, 6H).

Synthesis of 2- (benzyloxy) -1- (2,4-bis (benzyloxy) -6-hydroxyphenyl) ethanone (7)

Potassium carbonate (45.7 g, 331 mmol) was added to a solution of quercetin (6) (10 g, 33.1 mmol) in N, N-dimethylformamide (150 mL) and benzyl bromide mL, 331 mmol) was added thereto, followed by reflux stirring at 80 ^° C for 3 days (FIG. 3). After the reaction mixture was cooled to room temperature, potassium carbonate was filtered through filter paper and concentrated under reduced pressure. The resulting residue was recrystallized from dichloromethane / ethyl acetate. (25.2 g, 29.9 mmol) was added to anhydrous pyridine (80 mL) at room temperature to give the title compound Diethylene glycol (40 mL) and 18 N potassium hydroxide (40 mL) were added thereto, followed by reflux stirring at 120 ^° C for 12 hours. The reaction mixture is cooled to room temperature, neutralized with a 2 N aqueous hydrochloric acid solution, and extracted three times with dichloromethane (100 mL). The organic layer was washed with magnesium sulfate to remove water, concentrated under reduced pressure and purified by silica gel column chromatography (16: 1: 1 = hexane: dichloromethane: ethyl acetate) to obtain Compound 7 as a yellow solid. (4.0 g, 8.8 mmol, 29 % ^{yield): 1 H NMR (500 MHz} , CDCl 3) δ 13.74 (s, 1H), 7.21-7.39 (m, 15H), 6.18 (s, 1H), 6.06 (s, 1H), 5.05 (s, 2H), 4.98 (s, 2H), 4.56 (s, 2H), 4.52 (s, 2H).

Synthesis of 3,5-bis (benzyloxy) -2- (2- (benzyloxy) acetyl) phenyl 4- (methoxymethoxy) benzoate (8)

A solution of 2 (benzyloxy) -1- (2,4-bis (benzyloxy) -6-hydroxyphenyl) ethanone 7 (2 g, 4.4 mmol) and 4- (methoxymethoxy) benzoic acid 3 ) (0.8 g, 4.4 mmol) was dissolved in N, N-dimethylformamide (5 mL), and then 4-dimethylaminopyridine (DMAP) (0.54 g, Aminopropyl) carbodiimide (EDC) (2.05 g, 13.2 mmol). The mixture is stirred for 4 h at room temperature. The reaction mixture is concentrated under reduced pressure, and the residue is purified by column chromatography on a silica gel column (5: 1 = hexane: acetic acid ethyl ester) to obtain Compound 8 in the form of a pale yellow powder. (2.2 g, 3.6 mmol, 81 % ^{yield): 1 H NMR (400 MHz} , Acetone-d 6) δ 8.06 (d, J = 8.9 Hz, 2H), 7.50 (d, J = 8.9 Hz, 4H), 7.35 J = 2.1 Hz, 1H), 5.32 (s, 2H), 5.23 (m, 2H) (s, 2H), 5.19 (s, 2H), 4.51 (s, 2H), 4.40 (s, 2H), 3.46

Synthesis of 3,7-bis (benzyloxy) -4 '(methoxymethoxy) -camporol (9)

4- (methoxymethoxy) benzoate (8, 2.2 g, 3.6 mmol) was dissolved in toluene (10 mL). Potassium carbonate (1.8 g, 14.4 mmol) and tetrabutylammonium bromide (1.04 g, 3.2 mmol) were added to the mixture, and the mixture was refluxed at 90 ^° C for 4 hours. After the reaction mixture was cooled to room temperature, potassium carbonate was filtered through filter paper and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (4: 1 = hexane: acetone) to obtain Compound 9 in the form of yellow powder Can be obtained. (1.5 g, 2.5 mmol, 69 % ^{yield): 1 H NMR (400 MHz} , CDCl 3) δ 12.80 (s, OH), 7.97 (d, J = 9.0 Hz, 2H), 7.28-7.45 (m, 10H) , 7.09 (d, J = 9.0Hz, 2H), 6.50 (d, J = 2.2Hz, 1H), 6.44 , 5.07 (s, 2 H), 3.51 (s, 3 H).

Synthesis of 3,4'-bis (methoxymethoxy) -camprol (10):

(9.1 g, 1.96 mmol) was dissolved in methanol (2 mL) and tetrahydrofuran (4 mL), palladium / hydrogen peroxide was added to the solution of 3,7-bis (benzyloxy) charcoal (10%, 0.2 mmol) is added. The mixture is stirred for 4 hours in the presence of hydrogen. The reaction product is filtered through diatomaceous earth using acetone, and then concentrated under reduced pressure. The concentrate was dissolved in acetone (5 mL), followed by addition of potassium carbonate (0.25 g, 1.96 mmol) and methoxymethyl chloride (0.15 mL, 1.96 mmol), followed by stirring at room temperature for 2 hours. The residue was purified by column chromatography on silica gel column (3: 1 = hexane: acetic acid ethyl ester) to give 3,4'-bis ( Methoxymethoxy) -camperol (10). (0.55 g, 1.5 mmol, 75 % ^{yield): 1 H NMR (400 MHz} , Acetone-d 6) δ 12.80 (s, OH), 8.15 (d, J = 8.8 Hz, 2H), 7.09 (d, J = 2H), 6.74 (d, J = 2.1 Hz, 1H), 6.43 (d, J = 2.0 Hz, 1H), 5.30 (s, 4H), 3.45 (s, 6H).

Synthesis of camperol-3-O-beta-acetylated-glucoside (11)

Calcium carbonate (384 mg, 3 mmol) was dissolved in chloroform (3 mL) and water (3 mL). The solution was stirred at room temperature for 3 hours. . Compound (5) (1.23 g, 3 mmol) and Aliquat 336 (0.4 mL, 0.75 mmol) were added to the mixture and refluxed at 50 ^° C for 18 hours. The reaction mixture was washed with a 1 N aqueous hydrochloric acid solution, and the organic layer was washed with magnesium sulfate to remove water, concentrated under reduced pressure and purified by silica gel column chromatography (2: 1 = hexane: ethyl acetate 3 ester). To a solution of this compound (0.45 g, 0.75 mmol) in dichloromethane (6 mL) was added trifluoroacetic acid (3 mL) at 0 ^° C and stirred at room temperature for 4 hours. The reaction mixture is concentrated under reduced pressure, and the obtained residue is purified by silica gel column chromatography (1: 1 = hexane: acetone) to obtain Compound 11 in the form of a pale yellow powder. (0.25 g, 0.41 mmol, 53 % ^{yield): 1 H NMR (400 MHz} , Acetone-d 6) δ 12.80 (s, OH), 8.04 (d, J = 8.9 Hz, 2H), 6.88 (d, J = 2H), 6.72 (d, J = 2.1 Hz, 1H), 6.44 (d, J = 2.1 Hz, 1H), 5.62 (d, J = 7.9 Hz, 1H), 5.40-5.46 , 5.22-5.30 (m, 1H), 5.16-5.18 (m, 1H), 4.18-4.38 (m, 3H), 2.08 (s, 3H), 2.00 (s, 6H), 1.86 (s,

Synthesis of camperol-3-O-beta-glucoside (12):

Compound (11) having acetylated glucose bonded to Campulol 3 at position 3 was dissolved in methanol (3 mL) saturated with ammonia and stirred at room temperature for 6 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue was washed with diethyl ether to obtain camphorol-3-O-beta-glucoside (12): ¹ H NMR (400 MHz, MeOD) , 8.06 (d, J = 8.9 Hz, 2H), 6.90 (d, J = 8.9 Hz, 2H), 6.30 (d, J = 7.8 Hz, 1H), 3.69 (dd, J = 2.3,12.1 Hz, 1H), 3.55-3.59 (m, 1H), 3.43-3.53 (m, 3H), 3.23-3.36 ).

Example  2. Campulol -3-O- Glucoside  ( kaempferol -3-O- glucoside , KOG ) Inhibition test for melanin formation

In the melanogenesis inhibition assay, murine melanoma (B-16 F1) cells were inoculated with DMEM medium containing FBS (fetal bovine serum) and cultured at 37 ° C in 5% CO ₂ . Cells from which the medium was removed were washed with PBS (phosphatized buffer saline) and treated with trypsin to recover the cells. The recovered cells were centrifuged at 10,000 rpm for 10 minutes and then the supernatant was removed to obtain a pellet. The pellet was dried at 60 ° C and 100 μl of 1M NaOH (10% DMSO) was added to obtain intracellular melanin in a 60 ° C thermostat. The absorbance of this solution was measured at 490 nm to determine the amount of melanin. Arbutin, a whitening agent, was used as a control material in the KFDA. As shown in FIG. 4, KOG showed 90% efficacy compared to the reference drug arbutin.

Having described specific portions of the present invention in detail, it will be apparent to those skilled in the art that this specific description is only a preferred embodiment and that the scope of the present invention is not limited thereby. It will be obvious. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (9)

delete delete delete delete delete delete delete delete a-1) synthesizing methoxymethyl 4- (methoxymethoxy) benzoate by adding potassium carbonate and methoxymethyl chloride to a solution obtained by dissolving 4-hydroxybenzoic acid;
b) dissolving the methoxymethyl 4- (methoxymethoxy) benzoate in tetrahydrofuran and adding lithium hydroxide to synthesize 4- (methoxymethoxy) benzoic acid;
a-2) dissolving beta-D-glucose pentaacetate in dichloromethane and then adding bromic acid (HBr) to synthesize beta-D-tetraacetyl bromide;
a-3) To a solution obtained by dissolving quercetin in N, N-dimethylformamide, potassium carbonate was added, and benzyl bromide was added thereto. The obtained reaction mixture was cooled and then concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane / Acetic acid ethyl ester to dissolve 3,5,7-tris (benzyloxy) -2- (3,4-bis (benzyloxy) phenyl) -4H-chromen- And adding potassium hydroxide to synthesize 2- (benzyloxy) -1- (2,4-bis (benzyloxy) -6-hydroxyphenyl) ethanone;
c) A mixture of 2- (benzyloxy) -1- (2,4-bis (benzyloxy) -6-hydroxyphenyl) ethanone synthesized in the above a- Benzoic acid was dissolved in N, N-dimethylformamide and 4-dimethylaminopyridine and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC) Benzyloxy) -2- (2- (benzyloxy) acetyl) phenyl 4- (methoxymethoxy) benzoate;
d) dissolving the 3,5-bis (benzyloxy) -2- (2- (benzyloxy) acetyl) phenyl 4- (methoxymethoxy) benzoate obtained in the step c) in toluene, Adding tetrabutylammonium bromide to synthesize 3,7-bis (benzyloxy) -4 '(methoxymethoxy) -camphorol;
e) dissolving the 3,7-bis (benzyloxy) -4 '(methoxymethoxy) -camphorol obtained in step d) in methanol or tetrahydrofuran, adding palladium / charcoal, Dissolving the concentrated solution in acetone, adding potassium carbonate and methoxymethyl chloride to synthesize 3,4'-bis (methoxymethoxy) -camperol;
f) The 3,4'-bis (methoxymethoxy) -camphorol obtained in e) was dissolved in chloroform and water, and calcium carbonate was added. To this mixture was added the beta-D- Tetraacetylglucoside compound and Aliquat 336 were added and the mixture was refined. Then, trifluoroacetic acid was added to the solution in which the compound was dissolved in dichloromethane, and the mixture was stirred under reduced pressure to prepare camperol-3-O- Synthesizing acetylated-glucoside; and
g) dissolving the camphorol-3-O-beta-acetylated-glucoside obtained in step f) in ammonia-saturated methanol, and concentrating the reaction mixture under reduced pressure.

[Chemical Formula 1]

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