Polyphenol production method

Abstract

The present invention provides a novel method for synthesizing polyphenols. [Solution] A method for producing polyphenols, which comprises reacting catechins in the presence of an oxidizing agent and a catalyst, the catalyst comprising a metal oxide and / or a substrate having an inorganic material on its surface, and a composite having metal nanoparticles with a particle diameter of 0.5 nm or more and 100 nm or less, fixed to the surface of the inorganic material. [Selection diagram] None

Description

[Technical field]

[0001] The present invention relates to a method for producing polyphenols. [Background technology]

[0002] Japanese tea, which has been drunk by the Japanese people since ancient times, is attracting attention for its various functional substances. A representative example is catechins. The existence of these catechins was first confirmed in 1929 by Dr. Tsujimura and his colleagues at the RIKEN Institute. Since then, various functions have been discovered, such as antioxidant and antibacterial effects, cancer prevention, and blood cholesterol reduction, and they have been commercialized as beverages with special health claims and supplements.

[0003] However, the production of green tea, which contains a lot of catechins, is limited to certain regions such as Japan and China, and fermented teas such as black tea and oolong tea are produced in about 80% of the world. In recent years, it has been discovered that fermented tea also contains theaflavins, which have the same functions as catechins, and this has attracted attention (Patent Document 1). Methods for synthesizing theaflavins are also being researched (Patent Documents 2 and 3). In addition to catechin and theaflavin, polyphenols with number-average molecular weights of 9,000 to 18,000 have been found to be useful in terms of physiological activities such as inhibiting fat accumulation in the liver, and a method for extracting said polyphenols from fermented tea has been disclosed (Patent Document 4). Also, a method for producing oligomers by condensing catechin derivatives using a Lewis acid catalyst has been disclosed (Patent Document 5). In addition to catechin and theaflavin, a polyphenol composition obtained by heating an extract from a natural product in an acidic solution has also been disclosed (Patent Document 6). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2004-155784 A [Patent Document 2] JP 2010-035548 A [Patent Document 3] JP 2011-172514 A [Patent Document 4] JP 2012-005413 A [Patent Document 5] JP 2017-001982 A [Patent Document 6] International Publication No. 2006 / 090830 [Patent Document 7] International Publication No. 2015 / 198614 Summary of the Invention [Problem to be solved by the invention]

[0005] However, in the methods using enzyme reactions or cultured cells as described in Patent Documents 2 and 3, the conditions for synthesis are very strict, handling is poor, purification such as removing the enzyme after the reaction is not easy, and complicated steps such as chromatography are required, making them unsuitable for mass production. In addition, in the extraction from natural products as described in Patent Document 4, the extraction efficiency is low, and a separation and purification step from a crude extract is required to increase the purity, which makes the production process complicated. The method of Patent Document 5 does not directly oligomerize catechin, but requires a pre-step of protecting the hydroxyl group of catechin and introducing a leaving group before the condensation reaction, which is the oligomerization step, and a post-step of removing the protecting group after the condensation reaction, making it a complicated method requiring multiple steps. The composition of Patent Document 6 is a low molecular weight product obtained by cleaving a polymeric substance with an acid, but chemical cleavage with an acid produces substances with various molecular weights and structures, making it inefficient for obtaining the desired substance. In addition, it is difficult to control the decomposition reaction, making it difficult to prepare polyphenols with the desired molecular weight and structure.

[0006] The applicant has applied for a catalyst for synthesizing theaflavins and a method for synthesizing theaflavins using the same (Patent Document 7), but a method for synthesizing polyphenols other than theaflavins has not been made clear. An object of the present invention is to provide a novel method for synthesizing polyphenols. [Means for solving the problem]

[0007] That is, the gist of the present invention is as follows. [1] The method comprises reacting catechins in the presence of an oxidizing agent and a catalyst, The catalyst is Metal oxides, and / or A method for producing polyphenols, comprising: a substrate having an inorganic material on its surface; and a composite having metal nanoparticles, the particle diameter of which is 0.5 nm or more and 100 nm or less, fixed to the surface of the inorganic material. [2] The catalyst comprises the composite, The method for producing polyphenols according to [1], wherein the metal nanoparticles are one or more selected from the group consisting of Au, Pd, Pt, Rh, Ru, Ir, Ag, and oxides thereof. [3] The method for producing polyphenols described in [1] or [2], wherein the catalyst has the complex in which the metal nanoparticles are fixed to the surface of an inorganic material selected from the group consisting of one or more of SiO2, ZrO2, Fe2O3, Al2O3, C and TiO2. [4] A method for producing polyphenols described in any one of [1] to [3], wherein the catalyst has one or more metal oxides selected from the group consisting of WO3, Fe2O3, Ag2O and CuO. [5] The method for producing polyphenols described in any one of [1] to [4], wherein the oxidizing agent is hydrogen peroxide or oxygen. [6] The method for producing polyphenols according to any one of [1] to [5], wherein the molar ratio of the catechins to the oxidizing agent in the reaction is from 1:1 to 1:50. [7] The method for producing polyphenols according to any one of [1] to [6], wherein the reaction is carried out in a solvent at a temperature of 15°C or higher and lower than the boiling point of the solvent. [8] The method for producing polyphenols according to [7], wherein the solvent is water. [9] The method for producing a polyphenol according to any one of [1] to [8], wherein the number average molecular weight of the polyphenol is 9,000 or more and 18,000 or less. Effect of the Invention

[0008] According to the present invention, a novel method for synthesizing polyphenols can be provided. [Brief description of the drawings]

[0009] [Figure 1] 1 is an infrared absorption spectrum of the polyphenol obtained in Example 19. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The method for synthesizing polyphenols according to this embodiment will be described in detail below. The present embodiment relates to a method for synthesizing polyphenols, which comprises reacting catechins in the presence of an oxidizing agent and a catalyst for synthesizing polyphenols, which will be described later. Polyphenol refers to a compound having a plurality of phenolic hydroxyl groups, and in this specification, it particularly refers to compounds other than catechins that are classified as polyphenols based on their structure. Examples of polyphenols according to this embodiment include theaflavins obtained by reacting two molecules of catechins, and catechin polymers obtained by oxidative polymerization of catechins.

[0011] In the synthesis method of the present embodiment, the reaction is carried out using catechins as a starting material. Catechins are divided into pyrogallol-type catechins and catechol-type catechins. Catechol-type catechins include catechin (C), and stereoisomers of catechin such as epicatechin (EC) and epicatechin gallate (ECg). Pyrogallol-type catechins include epigallocatechin (EGC) and epigallocatechin gallate (EGCg). In this specification, catechins are defined as catechins represented by the following general formula (I) (wherein R 1 is a hydrogen atom or a galloyl group), or a compound represented by the general formula (II) 2 is a hydrogen atom or a galloyl group). Pyrogallol-type catechins are represented by the following general formula (I), and catechol-type catechins are represented by the following general formula (II). In this embodiment, one of these catechins may be used as a raw material, or a mixture of two or more of them may be used as a raw material. The catechins used as raw materials may be commercially available products or extracts from tea leaves.

[0012] [ka] [ka]

[0013] In formula (I), R 1 represents a hydrogen atom or a galloyl group. Epigallocatechin (EGC) is a compound represented by the formula (I) 1 is a hydrogen atom, and epigallocatechin gallate (EGCg) is a compound represented by the formula (I) 1 In the formula (II), R 2 represents a hydrogen atom or a galloyl group. Catechin (C) and epicatechin (EC) are represented by R 2 is a hydrogen atom, and epicatechin gallate (ECg) is a compound in which R 2 is a galloyl group.

[0014] In this embodiment, the reaction can be carried out, for example, in solution. The solvent used in the synthesis reaction is not particularly limited as long as it can dissolve catechins, but solvents known to those skilled in the art, such as water, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, formic acid, acetic acid, phosphoric acid, acetone, methyl ethyl ketone, methyl isobutyl ketone, acetonitrile, dichloromethane, N,N-dimethylformamide, dimethyl sulfoxide, and ethyl acetate, can be used alone or in combination. Water is highly safe and often dissolves the product polyphenols, making it a preferable reaction solvent.

[0015] Next, the catalyst for polyphenol synthesis used in this embodiment will be described. The catalyst for polyphenol synthesis according to this embodiment has a metal oxide and / or a composite. The composite comprises a substrate having an inorganic material on its surface, and metal nanoparticles having a particle diameter of 0.5 nm or more and 100 nm or less that are fixed to the surface of the inorganic material. In the composite, the metal nanoparticles are fixed to the inorganic material on the substrate surface, so that the composite has a very high oxidation catalytic ability. The metal nanoparticles can be fixed to the inorganic material by various methods described later.

[0016] The substrate of the composite usable in the present embodiment is not particularly limited as long as it has an inorganic material on its surface. Specific examples of the substrate include a substrate whose surface is made of an inorganic material and a substrate entirely made of an inorganic material. The inorganic material may be made of one or more of zeolite, apatite, carbon materials such as activated carbon, diatomaceous earth, metal oxides, etc. Of these, it is preferable that the inorganic material is made of a metal oxide. The method for forming a substrate having a metal oxide on its surface is not particularly limited, but includes a method for electrochemically forming a thin metal oxide film by anodization, a method for oxidizing a metal surface by heat treatment, a method for forming a thin oxide film by sputtering or ion plating, etc. The entire substrate may be made of a metal oxide. By making the inorganic material from a metal oxide, oxygen molecules are actively exchanged, so that catalytic activity can be further increased. As the metal oxide, oxides of silicon, zirconium, zinc, titanium, chromium, iron, copper, tin, aluminum, etc. are preferable, and for example, the inorganic material may be made of one or more of these metal oxides. In particular, it is more preferable that the inorganic material is made of one or more of SiO2, ZrO2, Fe2O3, Al2O3, C, and TiO2, since the catalytic activity is further increased in relation to the amount of metal nanoparticles fixed as described above, and it is even more preferable that the inorganic material is made of one or more of SiO2, Fe2O3, Al2O3, and TiO2.

[0017] As the metal nanoparticles according to this embodiment, it is preferable to select one or more from the group consisting of gold (Au), silver (Ag), palladium (Pd), platinum (Pt), rhodium (Rh), iridium (Ir), ruthenium (Ru) and their oxides, since it can increase the productivity of polyphenols. For the same reason, it is more preferable to use one or more from the group consisting of gold, palladium, platinum, rhodium, and iridium as the metal nanoparticles according to this embodiment.

[0018] In this specification, metal nanoparticles refer to metal particles with a particle size of less than 1 μm. In this embodiment, the average particle size of the metal nanoparticles is preferably 0.5 nm to 100 nm, more preferably 0.5 nm to 20 nm, and even more preferably 0.5 nm to 10 nm. An average particle size smaller than 0.5 nm is more likely to be unstable as a substance than one that is 0.5 nm or more, and an average particle size larger than 100 nm has a lower catalytic activity than one that is 100 nm or less. On the other hand, by making the average particle size 100 nm or less (more preferably 20 nm or less, and even more preferably 10 nm or less), the catalytic activity is further increased. The average particle size in this specification refers to the average value of the particle sizes of at least 300 metal nanoparticles actually measured using TEM images. The particle size can be adjusted, for example, by adjusting the pH of the solution during preparation of the metal nanoparticles based on a known method.

[0019] The method for fixing the metal nanoparticles to the inorganic material of the substrate is not particularly limited and can be appropriately set. For example, the metal nanoparticles may be fixed to the inorganic material on the substrate surface by a binder or by heating and drying. Alternatively, the colloid may be applied to the inorganic material portion of the substrate surface and then dried to fix the metal nanoparticles to the inorganic material. For example, when palladium or palladium oxide is fixed to an inorganic material, palladium ions may be adsorbed and fixed to the inorganic material by a chemical method such as zeta potential or diffusion of palladium ions. Alternatively, a substrate having an inorganic material on its surface may be immersed in an aqueous solution containing palladium ions to coat the substrate, and then immersed in an aqueous solution containing a reducing agent such as an organic acid, formaldehyde, or hydrazine, or reduced in a hydrogen reducing atmosphere to fix nanoparticles of palladium or palladium oxide to the inorganic material.

[0020] For example, the metal nanoparticles may have a shape such as a hemisphere, and may be bonded to the inorganic material in close contact, forming a peripheral portion of the bonded interface in the inorganic material by the bonding. In this case, the metal nanoparticles are directly bonded to the inorganic material by utilizing the difference in zeta potential between the inorganic material and the metal nanoparticles. Note that the bonding in this specification refers to the inorganic material and the metal nanoparticles being in contact with each other and fixed at a surface (bonded interface), and the peripheral portion of the bonded interface refers to the peripheral portion (perimeter) of the bonded interface. In addition, in this specification, the direct bonding refers to the inorganic material on the surface of the substrate and the metal nanoparticles being fixed without the intervention of other materials such as a binder.

[0021] The metal nanoparticles are directly bonded to the inorganic material on the surface of the substrate, and the peripheral portion of the bonded interface is exposed on the surface of the catalyst, and the catalyst having the peripheral portion of the bonded interface between the substrate and the metal nanoparticles acts on catechin, so that the synthesis reaction of polyphenols proceeds more. To explain this point in detail, it is presumed that oxygen defects are easily formed at the peripheral portion of the bonded interface, where the activation of oxygen molecules and hydrogen molecules proceeds. Therefore, in order to increase the activity and selectivity of the oxidation catalyst, it is advantageous to have the peripheral portion of the bonded interface. Therefore, in this embodiment, it is preferable to have a peripheral portion of the bonded interface formed by bonding between the metal nanoparticles and the inorganic material.

[0022] The method for fixing the metal nanoparticles to the inorganic material surface in a state where the peripheral portion of the bonded interface is formed by direct bonding is not particularly limited. Specific examples include coprecipitation, impregnation, sol-gel, drop neutralization precipitation, reducing agent addition, pH-controlled neutralization precipitation, carboxylate metal salt addition, colloid, deposition precipitation (DP), urea, deposition reduction, solid-phase mixing (SG), and coprecipitation (One-pot) methods, and these methods can be used appropriately depending on the type of inorganic material on the substrate surface.

[0023] The method for preparing the polyphenol synthesis catalyst of this embodiment using a gold compound will be specifically described below, taking the deposition precipitation method as an example. As a specific method for the deposition precipitation method, first, an aqueous solution in which a gold compound is dissolved is heated to 20 to 90°C, preferably 50 to 70°C, and while stirring, the solution is adjusted with an alkaline solution to a pH of 3 to 10, preferably 5 to 8. Thereafter, an inorganic material serving as a base is added to the aqueous solution, which is further stirred at 50 to 70°C, filtered, and calcined to obtain the polyphenol synthesis catalyst of this embodiment.

[0024] Examples of gold compounds that can be used to prepare the gold compound aqueous solution include HAuCl4·4H2O, NH4AuCl4, KAuCl4·nH2O, KAu(CN)4, Na2AuCl4, KAuBr4·2H2O, and NaAuBr4. The concentration of the gold compound in the gold compound aqueous solution is not particularly limited, but is preferably 1×10 -1 ~1×10 -5 It is preferable to use mol / L.

[0025] The amount of metal nanoparticles supported on the inorganic material is not particularly limited, but is preferably 0.5 to 30 mass% relative to the inorganic material, and more preferably 0.5 to 25 mass%. The reason why 0.5 to 25 mass% is more preferable is that if the metal nanoparticles are supported at a rate higher than 25 mass%, they tend to aggregate with each other, and the redox action is reduced compared to when the amount is within the range.

[0026] In the above-mentioned composite, the above-mentioned metal nanoparticles are fixed to the inorganic material on the surface of the substrate, and oxide particles of, for example, titanium, aluminum, iron, etc. may be further supported. The method for supporting the oxide particles on the surface of the inorganic material is not particularly limited, and for example, the oxide particles may be supported on the inorganic material by a thermal spraying method. The oxide particles supported on the inorganic material can suppress the adhesion of substances that inhibit the catalytic activity of the metal nanoparticles to the metal nanoparticles, so that the oxidation-reduction action can be stably maintained for a longer period of time.

[0027] The polyphenol synthesis catalyst may contain a metal oxide in place of the above complex or in addition to the above complex. The metal oxide that can be used is not particularly limited as long as it has oxidation catalytic ability, but Al2O3, Ag2O, CeO2, CuO, Cu2O, Fe2O3, MnO2, MoO3, V2O5, WO3, etc. are preferred. In particular, Ag2O, Fe2O3, WO3 and CuO increase the yield of polyphenols, so it is more preferable that the metal oxide is composed of at least one of these, and Ag2O and / or WO3 are even more preferred. The form is not particularly limited, but if it is particulate, it is preferable because the specific surface area is large and the catalytic activity is high. The metal oxide may also be fixed to a substrate. The above metal oxides may be used alone or in combination as a catalyst for polyphenol synthesis. Also, a metal oxide may be used in combination with the above complex.

[0028] The catalyst for polyphenol synthesis according to this embodiment can have various forms. The method of adjusting the shape is not particularly limited, and can be appropriately set by a person skilled in the art. When the catalyst for polyphenol synthesis has the above-mentioned complex, the catalyst can be molded into any shape, for example, by adjusting the shape of the substrate. For example, the catalyst for polyphenol synthesis according to this embodiment can be made to have a form such as a powder, granule, tablet form by pressure molding, etc. Furthermore, the catalyst for polyphenol synthesis according to this embodiment can have a form such as a filter form, sheet form, etc. by making the substrate a woven or knitted fabric, nonwoven fabric, or sheet made of a fibrous inorganic material, or by making a foil-shaped or plate-shaped metal oxide, etc., as the substrate.

[0029] Furthermore, when the polyphenol synthesis catalyst of this embodiment has the above-mentioned powder, granule, or tablet form formed by compression molding, the catalyst can be contained in a fiber structure or fixed to the outer surface of the fiber structure.

[0030] The specific treatment for containing or fixing the polyphenol synthesis catalyst of this embodiment in the fiber structure can be appropriately selected by a person skilled in the art, and is not particularly limited. For example, the polyphenol synthesis catalyst of this embodiment may be added to a polymer material, and then kneaded and spun to be contained in the fiber structure. The polyphenol synthesis catalyst may also be fixed to a fiber structure such as a woven fabric or nonwoven fabric using a binder or a coupling agent. Furthermore, after fixing the polyphenol synthesis catalyst to an inorganic material such as zeolite, the inorganic material to which the polyphenol synthesis catalyst is fixed may be fixed to a fiber structure to produce a polyphenol synthesis catalyst filter, or after fixing a base made of inorganic oxide particles, for example, to a fiber substrate, the substrate may be immersed in a hydrate in which a material for metal nanoparticles is dissolved, so that the metal nanoparticles are precipitated on the surface of the inorganic oxide particles, etc. In addition, in this specification, the inclusion of the polyphenol synthesis catalyst is a concept that also includes the case where the polyphenol synthesis catalyst is exposed on the outer surface of the fiber structure.

[0031] The binder component can be appropriately selected in consideration of the adhesion to the fiber substrate, and is not particularly limited. For example, as synthetic resins, polyester resins, amino resins, epoxy resins, polyurethane resins, acrylic resins, water-soluble resins, vinyl resins, fluororesins, silicone resins, cellulose resins, phenol resins, xylene resins, toluene resins, etc. can be used. In addition, as natural resins, drying oils such as castor oil, linseed oil, and tung oil can be used.

[0032] The method of fixing the polyphenol synthesis catalyst of the present embodiment to the fiber substrate may be by fixing with the above-mentioned binder, etc. Alternatively, the polyphenol synthesis catalyst of the present embodiment, which is chemically bonded to a silane monomer having an unsaturated bond by refluxing, etc., may be dispersed in a solvent such as methanol, applied to or immersed in a fiber substrate, and then irradiated with radiation such as an electron beam to chemically bond the catalyst by graft polymerization.

[0033] Examples of the silane monomers that can be used include vinyltrichlorosilane, vinyltrimethoxysilane, vinyltriethoxysilane, vinyltriacetoxysilane, N-β-(N-vinylbenzylaminoethyl)-γ-aminopropyltrimethoxysilane, N-(vinylbenzyl)-2-aminoethyl-3-aminopropyltrimethoxysilane hydrochloride, 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane, 3-glycidoxypropyltrimethoxysilane, 3-glycidoxypropylmethyldiethoxysilane, 3- Glycidoxypropyltriethoxysilane, p-styryltrimethoxysilane, 3-methacryloxypropylmethyldimethoxysilane, 3-methacryloxypropyltrimethoxysilane, 3-methacryloxypropylmethyldiethoxysilane, 3-methacryloxypropyltriethoxysilane, 3-acryloxypropyltrimethoxysilane, 3-isocyanatopropyltriethoxysilane, bis(triethoxysilylpropyl)tetrasulfide, 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane silane, 3-triethoxysilyl-N-(1,3-dimethyl-butylidene)propylamine, N-phenyl-3-aminopropyltrimethoxysilane, N-2-(aminoethyl)-3-aminopropylmethyldimethoxysilane, N-2-(aminoethyl)-3-aminopropyltrimethoxysilane, N-2-(aminoethyl)-3-aminopropyltriethoxysilane, 3-mercaptopropylmethyldimethoxysilane, 3-mercaptopropyltrimethoxysilane, N-phenyl-3-aminopropyltrimethoxysilane Examples of suitable silanes include silane, special amino silane, 3-ureidopropyl triethoxysilane, 3-chloropropyl trimethoxysilane, tetramethoxysilane, tetraethoxysilane, methyltrimethoxysilane, methyltriethoxysilane, dimethyldiethoxysilane, phenyltriethoxysilane, hexamethyldisilazane, hexyltrimethoxysilane, decyltrimethoxysilane, hydrolyzable group-containing siloxanes, fluoroalkyl group-containing oligomers, methylhydrogensiloxane, and silicone quaternary ammonium salts.

[0034] As a specific example of a method for producing a fiber structure, for example, a nonwoven fabric produced by entangling fibers, or a mixed paper produced by mixing pulp and a binder can be produced as a substrate by mixing the polyphenol synthesis catalyst of this embodiment, and the catalyst can be sandwiched in the space inside the substrate. In addition, a thermoplastic resin, a reactive hot melt adhesive, or a resin that reacts and hardens with particle beams such as ultraviolet rays or electron beams can be discharged in a fibrous form from a nozzle, and while the surface of the fiber formed by the discharge is sticky, the catalyst for polyphenol synthesis of this embodiment can be contacted, and then a reaction hardening process can be performed to fix the catalyst for polyphenol synthesis of this embodiment. The fixation can be performed by returning the hot melt adhesive to room temperature to fix it, by reacting and hardening it with moisture in the air in the reactive hot melt adhesive, or by irradiating ultraviolet rays or electron beams to react and harden it in the case of a resin that crosslinks with ultraviolet rays or electron beams.

[0035] Resins used in this way include hot melt adhesives whose main component is a resin such as low density polyethylene, linear low density polyethylene, polypropylene, ethylene vinyl acetate copolymer resin, ethylene-methyl methacrylate copolymer resin, or ethylene-ethyl acrylate copolymer resin; reactive hot melt adhesives whose main component is a urethane prepolymer; and resins that crosslink when exposed to ultraviolet light or electron beams and whose main components are polyurethane acrylate or polyester acrylate resin.

[0036] Next, the process for producing polyphenols will be described with an example. First, the raw catechins are added to a solvent and stirred to dissolve, to obtain a solution (hereinafter referred to as a catechin solution). The concentration of catechins in the catechin solution is not particularly limited and can be appropriately set by a person skilled in the art, but it is preferable that the ratio of the metal nanoparticle concentration (μmol / mL) and / or metal oxide concentration (μmol / mL) supported on the polyphenol synthesis catalyst to the total catechin concentration (μmol / mL) is 1:1 or more, since this can further increase the yield of polyphenols. The upper limit of the ratio of the metal nanoparticle concentration (μmol / mL) and / or metal oxide concentration (μmol / mL) to the total catechin concentration (μmol / mL) is not particularly limited, but since the reaction rate decreases when the catechin concentration is high relative to the catalyst concentration, it is preferable that the ratio is 1:1000 or less from the viewpoint of productivity. When water is used as a solvent, catechins are present stably, so it may be used in an acidic state. In order to increase the solubility of catechins, alcohols such as ethanol may be mixed into the catechin solution.

[0037] The oxidizing agent used in the reaction of this embodiment may be any oxidizing agent known to those skilled in the art, such as permanganates such as sodium permanganate, potassium permanganate, zinc permanganate, calcium permanganate, and magnesium permanganate, dichromates such as potassium dichromate, chromates such as potassium chromate, persulfates such as ammonium persulfate, sodium persulfate, and potassium persulfate, dilute nitric acid, oxygen gas, ozone, and hydrogen peroxide. Of these, oxygen gas and hydrogen peroxide are preferred because they are easy to handle. Oxygen gas can be easily supplied by bubbling into the catechin solution. In addition, hydrogen peroxide can be dissolved in the catechin solution before the reaction. Even if oxygen gas and hydrogen peroxide remain unreacted after the reaction is completed, they can be easily decomposed and removed by operations such as reduced pressure and heating or by natural evaporation, and they also have the advantage of being less likely to remain as impurities in the obtained polyphenol.

[0038] In the reaction of this embodiment, for example, the above-mentioned polyphenol synthesis catalyst and oxidizing agent are added to the above-mentioned catechin solution to allow the reaction to proceed. Regarding the amount of the oxidizing agent used in the reaction of this embodiment, the molar ratio of catechins to the oxidizing agent is preferably 1:1 to 1:200, and more preferably 1:1 to 1:50. If the proportion of oxidizing agent is less than 1:1 in the above molar ratio, the reaction will proceed more slowly than when it is within the range, the molecular weight of the produced polyphenol will be smaller, and more unreacted catechin will remain. In addition, the difference in molecular weight of the polyphenol obtained under the same reaction conditions is not so great between the case where the ratio of the oxidizing agent is more than 1:50 and the case where the ratio of the oxidizing agent is 1:50 or less, and the difference is even smaller between the case where the ratio of the oxidizing agent is more than 1:200 and the case where the ratio of the oxidizing agent is the same or less than 1:200. Therefore, there is less need to use a larger amount of oxidizing agent than the case where the molar ratio is 1:200.

[0039] The reaction temperature is not particularly limited as long as the solution exists in a liquid state, and is preferably from 4°C to the boiling point of the solvent, and more preferably from 15°C to the boiling point of the solvent, which increases the reaction efficiency of the catalyst. The higher the reaction temperature, the faster the reaction rate becomes, but a reaction at a temperature above the boiling point of the solvent requires a pressure-resistant vessel, which makes the reaction apparatus complicated, and is therefore not preferred.

[0040] The reaction is carried out, for example, with stirring, and when a certain time has elapsed, the reaction can be stopped by a method such as removing the catalyst. Since the molecular weight increases with reaction time, the reaction time may be adjusted according to the target molecular weight.

[0041] The polyphenol produced by the reaction of this embodiment is not particularly limited, but from the viewpoint of further enhancing the physiological activity, a polyphenol having a number average molecular weight of 3,000 to 20,000 is preferable. Furthermore, since the physiological activity is further enhanced, a polyphenol having a number average molecular weight of 9,000 to 18,000 is even more preferable. In addition, examples of the physiological activity include the inhibitory effect on fat accumulation in the liver and antioxidant activity, as described in Patent Document 4. In this embodiment, whether the reaction has progressed can be confirmed by measuring the molecular weight of the product and detecting that the product has a plurality of phenolic hydroxyl groups in its structure. The molecular weight of the product can be measured by a conventional instrumental analysis such as gel permeation chromatography, GPC-MALS, MALDI-TOFMS, etc. For example, in the examples described below, the number average molecular weight of the product polyphenol is shown as a polystyrene-equivalent molecular weight measured by gel permeation chromatography under the following conditions. Column: TSKgel α-3000 (Tosoh Corporation) Eluent: dimethylformamide containing 10 mM lithium chloride Flow rate: 0.6ml / min Temperature: 40℃ Detector: UV detector (measurement wavelength: 275 nm) Whether or not the product has multiple phenolic hydroxyl groups can be detected by, for example, infrared absorption spectrum measurement, absorbance measurement by the Folin-Ciocalteu method, etc. In addition, the presence of multiple phenolic hydroxyl groups may be confirmed by further identifying the molecular structure of the obtained compound by, for example, a known method.

[0042] After the reaction is completed, the suspension containing the obtained polyphenols and the catalyst for synthesizing polyphenols is centrifuged or passed through a filter or the like to remove the catalyst for synthesizing polyphenols, thereby obtaining a solution containing polyphenols (hereinafter referred to as a polyphenol solution). The obtained polyphenol solution may be used as it is, or the solvent may be removed from the polyphenol solution by evaporation, reprecipitation, or the like to isolate and recover the polyphenol. If necessary, low molecular weight components such as unreacted catechins may be removed or particularly active components may be extracted by methods such as dialysis or chromatography. Furthermore, the catalyst for polyphenol synthesis separated by centrifugation or the like can be repeatedly used for polyphenol synthesis.

[0043] As described above, in this embodiment, unlike the case where the reaction is carried out using an enzyme or the like, the catalyst can be easily removed from the product after polyphenol production by a method such as filtration, and the process is simple. In addition, when the reaction is carried out using an enzyme or the like, efficient synthesis is not possible unless special conditions such as temperature and pH are met, but in this embodiment, the reaction can be carried out efficiently under a wider range of reaction conditions, and therefore polyphenols of various structures and molecular weights can be produced by selecting the starting material and reaction conditions. In addition, in the conventional chemical synthesis method, an organic solvent is required, and pretreatment such as introduction of a protective group to catechin may be required, but in this embodiment, the reaction can be carried out in an aqueous solvent that is less burdensome to the environment, and it is a simple and safe production method that does not require treatment before or after the reaction. EXAMPLES

[0044] The present invention will now be described in more detail with reference to examples, although the present invention is not limited to these examples. (Preparation of catalyst for polyphenol synthesis) (Production Example 1): Pd A palladium chloride aqueous solution was weighed and dissolved in 1.5 mL of distilled water so that the amount of palladium supported on the substrate was 1 wt%, and 50 μL of ethylene glycol was added to prepare a complex solution. 1 g of titanium oxide powder was weighed as the substrate, and 1.5 mL of distilled water was added to suspend it. The complex solution was then added to the titanium oxide powder suspension on the substrate while stirring, and dried in a 60°C dryer until all moisture was removed to obtain a powder. This dried powder was calcined at 250°C for 1 hour and pulverized to obtain a palladium nanoparticle-supported polyphenol synthesis catalyst. The particle size of the supported palladium nanoparticles was 12.5 nm.

[0045] (Example 2): Ir A polyphenol synthesis catalyst supported on iridium nanoparticles was obtained in the same manner as in Production Example 1, except that iridium chloride was used instead of palladium chloride. The particle size of the supported iridium nanoparticles was 5.7 nm.

[0046] (Production example 3): Ag A silver nanoparticle-supported polyphenol synthesis catalyst was obtained in the same manner as in Production Example 1, except that silver nitrate was used instead of palladium chloride. The particle size of the supported silver nanoparticles was 9.8 nm.

[0047] (Production example 4): Pt A platinum nanoparticle-supported polyphenol synthesis catalyst was obtained in the same manner as in Production Example 1, except that palladium chloride was replaced with chloroplatinic acid and the substrate was replaced with silicon oxide. The particle size of the supported platinum nanoparticles was 6.8 nm.

[0048] (Manufacturing example 5): Au 0.5 mmol of chloroauric acid was dissolved in 100 mL of water, heated to 70°C, and adjusted to pH 7.0 with NaOH aqueous solution. 1 g of titanium oxide powder was added to the aqueous solution as a substrate and stirred for 1 hour. The mixture was then separated into solid and liquid, dried under reduced pressure, calcined at 300°C for 4 hours, and pulverized to obtain a gold nanoparticle-supported polyphenol synthesis catalyst. The particle size of the supported gold nanoparticles was 1.8 nm.

[0049] (Polyphenol synthesis) Example 1 Epicatechin (EC) and epigallocatechin (EGC) were added as raw materials to pure water to make a concentration of 3.2 mM, and dissolved to obtain an aqueous catechin solution. 2 mL of the resulting aqueous catechin solution was placed in a 5 mL tube, and 100 μL of 3% hydrogen peroxide was added to the tube to obtain a reaction solution. The molar ratio of catechins to hydrogen peroxide was 1:25. 13 mg of the palladium nanoparticle-supported catalyst prepared in Production Example 1 was weighed and added to the mixture, and the mixture was stirred overnight. After the reaction was completed, the reaction solution was passed through a 0.45 μm pore size filter to remove the catalyst, and then the water was evaporated to obtain polyphenols.

[0050] Example 2 The catalyst was changed to the iridium nanoparticle-supported catalyst prepared in Production Example 2, and the reaction was carried out in the same manner as in Example 1 to obtain polyphenols.

[0051] Example 3 The catalyst was changed to the silver nanoparticle-supported catalyst prepared in Production Example 3, and the reaction was carried out in the same manner as in Example 1 to obtain polyphenols.

[0052] Example 4 The catalyst was changed to the platinum nanoparticle-supported catalyst prepared in Production Example 4, and the reaction was carried out in the same manner as in Example 1 to obtain polyphenols.

[0053] Example 5 The catalyst was changed to the gold nanoparticle-supported catalyst prepared in Production Example 5, and the reaction was carried out in the same manner as in Example 1 to obtain polyphenols.

[0054] Example 6 The catalyst was changed to a commercially available 1% gold-supported iron oxide catalyst (HarutaGold Co., Ltd.), and the reaction was carried out in the same manner as in Example 1 to obtain polyphenols.

[0055] Example 7 The catalyst was changed to a commercially available 1% gold-supported carbon (Ketjen Black) catalyst (HarutaGold Co., Ltd.), and the reaction was carried out in the same manner as in Example 1 to obtain polyphenols.

[0056] Example 8 The catalyst was changed to a commercially available 5% rhodium-supported alumina catalyst (Wako Pure Chemical Industries, Ltd.), and the reaction was carried out in the same manner as in Example 1 to obtain polyphenols.

[0057] Example 9 The catalyst was changed to a commercially available 0.5% ruthenium-supported alumina catalyst (NE Chemcat Corporation), and the reaction was carried out in the same manner as in Example 1 to obtain polyphenols.

[0058] Example 10 The catalyst was changed to commercially available silver oxide (Wako Pure Chemical Industries, Ltd.), and the reaction was carried out in the same manner as in Example 1 to obtain polyphenols.

[0059] Example 11 The catalyst was changed to commercially available copper oxide (Wako Pure Chemical Industries, Ltd.), and the reaction was carried out in the same manner as in Example 1 to obtain polyphenols.

[0060] Example 12 The catalyst was changed to commercially available tungsten oxide (Junsei Chemical Co., Ltd.), and the reaction was carried out in the same manner as in Example 1 to obtain polyphenols.

[0061] (Example 13) The catalyst was changed to commercially available iron oxide (HarutaGold Co., Ltd.), and the reaction was carried out in the same manner as in Example 1 to obtain polyphenols.

[0062] Example 14 The reaction was carried out in the same manner as in Example 5, except that the raw catechins were epicatechin (EC) alone, to obtain polyphenols.

[0063] Example 15 The reaction was carried out in the same manner as in Example 5, except that the raw catechin was epigallocatechin (EGC) alone, to obtain polyphenols.

[0064] (Example 16) The reaction was carried out in the same manner as in Example 5, except that the raw catechin was epicatechin gallate (ECg) alone, to obtain polyphenols.

[0065] (Example 17) The reaction was carried out in the same manner as in Example 5, except that the raw catechins were epigallocatechin gallate (EGCg) alone, to obtain polyphenols.

[0066] (Example 18) The reaction was carried out in the same manner as in Example 5, except that the raw catechins were catechin (C) alone, to obtain polyphenols.

[0067] (Example 19) Epigallocatechin gallate (EGCg) was added as a raw material to pure water to make a concentration of 156 mM, and dissolved to obtain an aqueous catechin solution. 2 mL of the resulting aqueous catechin solution was placed in a 5 mL tube, and 50 μL of 30% hydrogen peroxide was added to make a reaction solution. The molar ratio of catechins to hydrogen peroxide was 1:5.2. 66 mg of the gold nanoparticle-supported catalyst prepared in the Production Example was weighed out and added thereto, and the mixture was stirred at 60°C for 0.5 hours. After the reaction was completed, the reaction solution was passed through a 0.45 μm pore size filter to remove the catalyst, and then the water was removed by evaporation to obtain polyphenols.

[0068] (Example 20) The reaction was carried out in the same manner as in Example 19, except that the reaction time was changed to 1 hour, to obtain polyphenols.

[0069] Example 21 The reaction was carried out in the same manner as in Example 19, except that the reaction time was changed to 24 hours, to obtain polyphenols.

[0070] Example 22 The reaction was carried out in the same manner as in Example 19, except that the amount of 30% hydrogen peroxide solution added was changed to 100 μL (the molar ratio of catechins to hydrogen peroxide was 1:10.4), to obtain polyphenols.

[0071] (Example 23) The reaction was carried out in the same manner as in Example 19, except that the amount of 30% hydrogen peroxide water added was changed to 25 μL (the molar ratio of catechins to hydrogen peroxide was 1:2.6) and the reaction time was changed to 1 hour, to obtain polyphenols.

[0072] Comparative Example 1 The catalyst was changed to commercially available silicon oxide (HarutaGold Co., Ltd.), and the reaction was carried out in the same manner as in Example 1 to obtain polyphenols.

[0073] Comparative Example 2 The reaction was carried out in the same manner as in Example 1, except that no catalyst was added, to obtain polyphenols.

[0074] Comparative Example 3 The reaction was carried out in the same manner as in Example 19, except that hydrogen peroxide was not added, to obtain polyphenols.

[0075] (Confirmation of the presence of multiple phenolic hydroxyl groups and molecular weight measurement (confirmation of polyphenol production)) The product was confirmed to be a polyphenol as follows. The products of each of the Examples and Comparative Examples were subjected to infrared absorption spectroscopy to check for the presence or absence of a peak (3500-3200 cm-1) indicating a hydroxyl group, and absorbance measurement (wavelength: 765 nm) according to the Folin-Ciocalteu method based on ISO 14502-1:2005, confirming that they have multiple phenolic hydroxyl groups. FIG. 1 shows an example of the infrared absorption spectrum of the polyphenol obtained in Example 19.

[0076] The product was analyzed by gel permeation chromatography (GPC) to calculate the amount of the product. The product had a polystyrene-equivalent molecular weight of 3,000 or more. The amount of the product was expressed as the ratio of the area of ​​the product component to the area of ​​the entire peak in GPC. At the same time, the number average molecular weight of the product was calculated. The column used was TSKgel α-3000 (Tosoh Corporation), and the molecular weight was calculated using standard polystyrene. The detection wavelength was 275 nm.

[0077] The results regarding the amount of the product and the number average molecular weight are shown in Table 1. As shown in Table 1, production of polyphenols was confirmed in Examples 1 to 23, but was hardly confirmed in Comparative Examples 1 to 3.

[0078] [Table 1]

[0079] As described above, polyphenols can be easily synthesized by using the production method of the present invention.

Claims

1. The method comprises reacting catechins in a solution in the presence of an oxidizing agent, which is hydrogen peroxide, and a catalyst, The catalyst is Metal oxides, and / or A composite body including a substrate having an inorganic material on a surface thereof, and metal nanoparticles having a particle diameter of 0.5 nm or more and 100 nm or less, which are fixed to the surface of the inorganic material, A method for producing polyphenols having a number average molecular weight of 9,000 or more and 18,000 or less, wherein the molar ratio of the catechins to the oxidizing agent in the reaction in the solution is 1:1 to 1:

50.

2. The catalyst comprises the composite, The method for producing polyphenols according to claim 1, wherein the metal nanoparticles are one or more selected from the group consisting of Au, Pd, Pt, Rh, Ru, Ir, Ag and oxides thereof.

3. The catalyst is SiO 2 , ZrO 2 , Fe 2 O 3 , Al 2 O 3 , C and TiO 2 The method for producing polyphenols according to claim 1 or 2, wherein the complex has the metal nanoparticles fixed to the surface of one or more inorganic materials selected from the group consisting of:

4. The catalyst is WO 3 , Fe 2 O 3 , Ag 2 The method for producing polyphenols according to any one of claims 1 to 3, wherein the metal oxide is one or more selected from the group consisting of O and CuO.

5. The method for producing polyphenols according to any one of claims 1 to 4, wherein the reaction is carried out in a solvent at a temperature of 15°C or higher and not higher than the boiling point of the solvent.

6. The method for producing polyphenols according to claim 5, wherein the solvent is water.

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