WO2019151299A1 - Procédé de production d'un dérivé de glutaraldéhyde provenant d'un matériau naturel - Google Patents

Procédé de production d'un dérivé de glutaraldéhyde provenant d'un matériau naturel Download PDF

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WO2019151299A1
WO2019151299A1 PCT/JP2019/003098 JP2019003098W WO2019151299A1 WO 2019151299 A1 WO2019151299 A1 WO 2019151299A1 JP 2019003098 W JP2019003098 W JP 2019003098W WO 2019151299 A1 WO2019151299 A1 WO 2019151299A1
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producing
glutaraldehyde
glutaraldehyde derivative
iridoid compound
reaction
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富永　健一
康広 嶋本
礒田　博子
浅川　真澄
佐藤　一彦
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国立研究開発法人産業技術総合研究所
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Publication of WO2019151299A1 publication Critical patent/WO2019151299A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
    • C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
    • C07C45/60—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/28—Saturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings
    • C07C47/36—Saturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings containing hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J21/00—Catalysts comprising the elements, oxides, or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium, or hafnium
    • B01J21/12—Silica and alumina
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J21/00—Catalysts comprising the elements, oxides, or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium, or hafnium
    • B01J21/16—Clays or other mineral silicates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J27/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
    • B01J27/02—Sulfur, selenium or tellurium; Compounds thereof
    • B01J27/053—Sulfates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J29/00—Catalysts comprising molecular sieves
    • B01J29/04—Catalysts comprising molecular sieves having base-exchange properties, e.g. crystalline zeolites
    • B01J29/06—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof
    • B01J29/08—Crystalline aluminosilicate zeolites; Isomorphous compounds thereof of the faujasite type, e.g. type X or Y
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B61/00—Other general methods

Definitions

  • the present invention uses a naturally occurring iridoid compound as a raw material and reacts in the presence of a solid acid or a liquid acid catalyst having a pKa of 5 or less, and is added to the pyran ring in the raw iridoid compound.
  • the present invention relates to a technique for producing a glutaraldehyde derivative having a structure.
  • Non-Patent Document 1 oleocantal, which is one of glutaraldehyde derivatives present in olives, exhibits an anti-inflammatory analgesic effect equivalent to ibuprofen.
  • Non-Patent Document 2 discloses a method for total synthesis of oleacein in 10 steps using D-ribose as a starting material.
  • oleuropein which is a kind of iridoid compound abundantly contained in olive leaves, is used as a raw material and heated in the presence of 2 equivalents of chloride salt and 10 equivalents of water. Shows a method for synthesizing oleacein with a yield of 22%.
  • Patent Document 1 uses 2-alkoxy-3,4-dihydro-2H-pyran as a raw material in the presence or absence of water-soluble acid in water. The method of heat treatment is shown.
  • the inventor of the present invention examined the conventional synthesis method of the glutaraldehyde derivative as described above, and recognized that the following problems (1) and (2) exist.
  • the present invention is based on the background of the prior art as described above and the inventor's recognition of the prior art, and uses a naturally occurring iridoid compound as a raw material and adds it to the pyran ring in the raw iridoid compound. It is an object of the present invention to provide a novel production method for producing a glutaraldehyde derivative having a substituent structure.
  • the inventors generally used a naturally occurring iridoid compound having a structure represented by [Chemical Formula 2] as a raw material, and a solid acid catalyst having a pKa of 5 or less that is easily available in an organic solvent, such as zeolite, By adding silica alumina, sulfated zirconia, bentonite, polystyrene sulfonic acid or the like, or by using a liquid acid catalyst having a pKa of 5 or less as a catalyst in an organic solvent, it is added to the pyran ring in the raw material compound. It was found that a glutaraldehyde derivative having a certain substituent structure can be obtained in a relatively high yield.
  • X represents sugar or hydrogen, and at least one of R 1 , R 2 , and R 3 represents a substituent containing one or more selected from alkene, carboxylic acid, ester, and alcohol.
  • this application provides the following inventions.
  • a method for producing a glutaraldehyde derivative having at least one substituent structure added to a pyran ring in a raw material iridoid compound using a naturally occurring iridoid compound as a raw material, and having a pKa of 5 as a catalyst A method for producing a glutaraldehyde derivative, characterized by using the following solid acid or liquid acid.
  • (2) In the manufacturing method of the said glutaraldehyde derivative the manufacturing method of the derivative as described in said (1) whose water content in a reaction system is 1000 molar equivalent or less with respect to the iridoid compound used as a raw material.
  • a naturally occurring iridoid compound is used as a raw material in a relatively high yield, and at least one substituent structure added to the pyran ring in the raw material is retained. It becomes possible to produce a glutaraldehyde derivative.
  • the present invention is a method for producing a glutaraldehyde derivative having a substituent structure added to a pyran ring in a raw material iridoid compound using a naturally occurring iridoid compound as a raw material, and having a pKa of 5 or less as a catalyst.
  • a liquid acid is used.
  • the iridoid compound derived from a natural product used as a raw material is not particularly limited as long as it has the structure shown in the above [Chemical Formula 2]. Scandside and the like.
  • the oleuropein is abundant in olive leaves.
  • These purities are not particularly limited, and can be used as raw materials as a crude product.
  • a raw material may be supplied in a water-containing state, and may be supplied through a drying process.
  • the conversion reaction of the iridoid compound is usually performed in an organic solvent.
  • the organic solvent to be used is not particularly limited.
  • the solid acid catalyst having a pKa of 5 or less is not particularly limited.
  • zeolite, silica alumina, sulfated zirconia, bentonite and polystyrene sulfonic acid are used.
  • the zeolite is preferably a proton-substituted zeolite.
  • Bentonite is preferably substituted with at least one ion selected from proton, titanium, and copper.
  • liquid acid catalyst having a pKa of 5 or less examples include hydrochloric acid, hydrofluoric acid, bromic acid, iodic acid, sulfuric acid, phosphoric acid, nitric acid, carboxylic acid, ascorbic acid and the like.
  • the amount of water in the reaction system when using a liquid acid catalyst is preferably 1000 molar equivalents or less, more preferably 100 molar equivalents or less, and even more preferably 20 molar equivalents or less with respect to the iridoid compound as a raw material.
  • the amount of these catalysts used is 0.01 wt% to 1000 wt%, preferably 0.1 wt% to 400 wt%, more preferably 1 wt% to 200 wt%, based on the naturally occurring iridoid compound as a raw material. . If the amount of catalyst used is too small, the reaction will not proceed sufficiently, and if the amount of catalyst used is too large, operational problems will occur.
  • the reaction method of the present invention is not particularly limited, but a method in which a solid acid catalyst or liquid acid catalyst having a pKa of 5 or less is preferably added to an organic solvent in which the raw material is dissolved, and the reaction is performed by heating is exemplified. Moreover, the method of distribute
  • the reaction temperature is preferably 60 ° C. to 200 ° C., more preferably 120 ° C. to 160 ° C. When the reaction temperature is lower than this, the reaction rate becomes slow. When the reaction temperature is higher than this, the starting iridoid compound or the produced glutaraldehyde derivative is decomposed or modified.
  • a glutaraldehyde derivative having a structure can be produced.
  • the substituent structure in the raw material compound is not decomposed, and when a solid acid catalyst is used, the catalyst used in the reaction can be easily removed by solid-liquid separation and recovered. Since the catalyst can be reused repeatedly, various existing problems can be overcome.
  • Example 1-2 In Example 1-1, Example 1 was used except that 20 mg of silica alumina (manufactured by Wako Pure Chemical Industries, SiO 2 82.3%, Al 2 O 3 12.6%) was used instead of Y-type zeolite as the solid acid. As a result of carrying out the reaction in the same manner as in -1, oleacein was obtained in a yield of 60%.
  • silica alumina manufactured by Wako Pure Chemical Industries, SiO 2 82.3%, Al 2 O 3 12.6%
  • Example 1-1 In Example 1-1, the reaction was conducted in the same manner as in Example 1-1 except that 20 mg of sulfated zirconia (manufactured by Wako Pure Chemical Industries, Ltd.) was used in place of Y-type zeolite as the solid acid. As a result, oleacein was recovered. Obtained at a rate of 71%.
  • Example 2 ⁇ Production of oleacein with inorganic acid> Example 2-1
  • 10 mg of oleuropein manufactured by Toronto Research Chemicals, purity 75%) and 10 ⁇ L (10 mol%) of a 0.14 M aqueous hydrochloric acid solution (12N hydrochloric acid is purchased from Fuji Film Wako Pure Chemical Industries, Ltd.) are added as an organic solvent.
  • Add 0.5 mL of sulfoxide (Fuji Film Wako Pure Chemical Industries) containing 1.36 mg of water, 0.076 mmol, measured by Karl Fischer titration method
  • the reaction was carried out for 12 hours while stirring at 350 rpm. When the solution after the reaction was confirmed by NMR, a decomposition product was confirmed.
  • Example 2-2 In Example 2-1, except that 10 ⁇ L (1 mol%) of a 0.014 M hydrochloric acid aqueous solution was added, the reaction was carried out in the same manner as in Example 2-1. As a result, oleacein was obtained in a yield of 54%.
  • Example 2-3 The reaction was conducted in the same manner as in Example 2-1, except that 10 ⁇ L (0.1 mol%) of a 0.0016 M aqueous hydrochloric acid solution was added. When the solution after the reaction was quantified by NMR using the methyl group of tetramethylbenzene as an internal standard, oleacein was obtained in a yield of 67%. Further, 10 mL of pure water and 10 mL of ethyl acetate (Kishida Chemical) were added to the obtained reaction solution to carry out a liquid separation treatment.
  • the ethyl acetate phase was recovered, dried using sodium sulfate (Fuji Film Wako Pure Chemical Industries) as the desiccant, filtered, and the filtrate was concentrated to obtain an oily substance.
  • sodium sulfate Fluji Film Wako Pure Chemical Industries
  • the filtrate was concentrated to obtain an oily substance.
  • silica gel column chromatography manufactured by Kanto Chemical Co., Inc.
  • the ratio of hexane and ethyl acetate was changed from 10: 1 to 1: 1
  • 2.7 mg of oleacein (recovered) was obtained. 61%).
  • Example 3 ⁇ Production of oleacein with organic acid>
  • 10 mg of oleuropein (manufactured by Toronto Researchs Chemical, purity 75%) and 0.24 mg (10 mol%) of paratoluenesulfonic acid (manufactured by Kishida Chemical) were added to a glass tube with an internal volume of 2 mL, and dimethyl sulfoxide (Fuji Film Wako Pure) 0.5 mL of water (containing 1.36 mg of water, measured by Karl Fischer titration), and allowed to react for 12 hours under stirring at 350 rpm using a magnetic stirrer at 150 ° C. in an oil bath It was.
  • the solution after the reaction was quantified by NMR using the methyl group of tetramethylbenzene as an internal standard, oleacein was obtained in a yield of 54%.
  • Example 3-2 In Example 3-1, except that 24 ⁇ g (1 mol%) of p-toluenesulfonic acid (manufactured by Kishida Chemical Co., Ltd.) was added, the reaction was carried out in the same manner as in Example 2-1. As a result, oleacein was obtained in a yield of 73%. It was.
  • Example 3-3 As a result of carrying out the reaction in the same manner as in Example 3-1, except that 2.4 ⁇ g (0.1 mol%) of p-toluenesulfonic acid (manufactured by Kishida Chemical Co., Ltd.) was added.
  • 2.4 ⁇ g (0.1 mol%) of p-toluenesulfonic acid manufactured by Kishida Chemical Co., Ltd.
  • oleacein was obtained in a yield of 77%.
  • 10 mL of pure water and 10 mL of ethyl acetate (Kishida Chemical) were added to the obtained reaction solution to carry out a liquid separation treatment.
  • the ethyl acetate phase was recovered, dried using sodium sulfate (Fuji Film Wako Pure Chemical Industries) as the desiccant, filtered, and the filtrate was concentrated to obtain an oily substance.
  • sodium sulfate Fluji Film Wako Pure Chemical Industries
  • the filtrate was concentrated to obtain an oily substance.
  • Example 4 ⁇ Change in yield depending on the amount of solid acid>
  • Example 4-1 A glass tube with an internal volume of 2 mL was charged with oleuropein (manufactured by Toronto Research Chemicals, purity 75). %) 10 mg, bentonite (Kunimine F, Kunipia F, H + substituted type) as solid acid catalyst, 5 mg, dimethyl sulfoxide as organic solvent, 0.5 mL (containing 1.36 mg of water, measured by Karl Fischer titration method)
  • the reaction was allowed to stand at 150 ° C. for 12 hours in an oil bath.
  • the solution after the reaction was quantified by NMR using the methyl group of tetramethylbenzene as an internal standard, oleacein was obtained in a yield of 29%.
  • Example 4-2 In Example 4-1, reaction was carried out in the same manner as in Example 4 except that 10 mg of bentonite (Kunimine F, Kunipia F, H + substituted type) was added. As a result, oleacein was obtained in a yield of 69%. It was.
  • bentonite Korean F, Kunipia F, H + substituted type
  • Example 4-3 In Example 4-1, the reaction was carried out in the same manner as in Example 4-1, except that 20 mg of bentonite (Kunimine F, Kunipia F, H + substituted type) was added. As a result, oleacein was obtained in a yield of 82%. It was.
  • bentonite Korean F, Kunipia F, H + substituted type
  • Example 4-4 The reaction was carried out in the same manner as in Example 4-1, except that 40 mg of bentonite (Kunimine F, Kunipia F, H + substituted type) was added. As a result, oleacein was obtained in 89% yield. It was.
  • Example 5 ⁇ Change in yield with reaction time> A glass tube with an internal volume of 2 mL was charged with oleuropein (manufactured by Toronto Research Chemicals, purity 75). %) 10 mg, bentonite (Kunimine F, Kunipia F, H + substituted type) as solid acid catalyst, 5 mg, dimethyl sulfoxide as organic solvent, 0.5 mL (containing 1.36 mg of water, measured by Karl Fischer titration method) In addition, the reaction was allowed to stand in an oil bath at 150 ° C. for 2, 4, 6, 8, 10, and 12 hours. The solution after the reaction was quantified by NMR using the methyl group of tetramethylbenzene as an internal standard. The yield of oleacein was 2% 29%, 4 hours 25%, 6 hours 35%, 8 hours 75%, 10 hours. 80%, 12 hours 82%).
  • Example 6 ⁇ Change in yield due to water content> A glass tube with an internal volume of 2 mL was charged with oleuropein (manufactured by Toronto Research Chemicals, purity 75). %) 10 mg, 5 mg bentonite (Kunimine F, H + substituted type manufactured by Kunimine Kogyo Co., Ltd.) as a solid acid catalyst, 0.5 mL of dimethyl sulfoxide having a different water content as an organic solvent (using Karl Fischer titration method) Dimethyl sulfoxide containing 3, 7, 22, and 37 equivalents of water was prepared), and the mixture was allowed to stand at 150 ° C. for 12 hours in an oil bath.
  • oleuropein manufactured by Toronto Research Chemicals, purity 75.
  • bentonite Karl Fischer titration method
  • Example 7 ⁇ Change in yield with reaction temperature> A glass tube with an internal volume of 2 mL was charged with oleuropein (manufactured by Toronto Research Chemicals, purity 75). %) 10 mg, bentonite (Kunimine Industries Kunipia F, H + substituted type) 20 mg as solid acid catalyst, 0.5 mL of dimethyl sulfoxide as organic solvent (containing 1.36 mg of water, measured by Karl Fischer titration method) In addition, the reaction was allowed to stand at 125 ° C. in an oil bath. Every 12 hours, the reaction solution was quantified by NMR using the methyl group of tetramethylbenzene as an internal standard. As a result, oleacein was obtained in a yield (12 hours 22%, 24 hours 68%, 36 hours 76%).
  • Example 8-1 A glass tube with an internal volume of 2 mL was charged with oleuropein (manufactured by Toronto Research Chemicals, purity 75). %) 10 mg, bentonite (Kunimine Industries Kunipia F, H + substituted type) 20 mg as a solid acid catalyst, 0.5 mL of gamma-butyrolactone as an organic solvent (1.36 mg of water using Karl Fischer titration method) In addition, the mixture was allowed to stand at 150 ° C. for 12 hours in an oil bath.
  • oleuropein manufactured by Toronto Research Chemicals, purity 75.
  • bentonite Korean Industries Kunipia F, H + substituted type
  • Example 8-2 In Example 8-1, the reaction and post-treatment were performed in the same manner as in Example 8-1, except that diethylene glycol dimethyl ether (diglyme) was added instead of gamma-butyrolactone. As a result, 1.4 mg (yield 32%) of oleacein was obtained.
  • diethylene glycol dimethyl ether diglyme
  • Example 8-3 In Example 8-1, the reaction and post-treatment were performed in the same manner as in Example 8-1, except that enmethylpyrrolidine was added instead of gamma-butyrolactone. As a result, oleacein could not be obtained.
  • Example 8-4 In Example 8-1, the reaction and post-treatment were performed in the same manner as in Example 8-1, except that 1-octanol was added instead of gamma-butyrolactone. As a result, oleacein could not be obtained.
  • Example 8-5 The reaction and post-treatment were carried out in the same manner as in Example 8-1, except that dimethyl sulfoxide was added instead of gamma-butyrolactone. As a result, 3.5 mg (yield 80%) of oleacein was obtained.
  • Example 9 ⁇ Production of oleocanthal with solid acid catalyst>
  • 11 mg of ligustroside 22 mg of bentonite (Kunimine Industries Kunipia F, H + substituted type) as a solid acid catalyst
  • 0.5 mL of dimethyl sulfoxide as an organic solvent containing 1.36 mg of water, (Measured by Karl Fischer titration method)
  • 10 mL of pure water and 10 mL of ethyl acetate (Kishida Chemical) were added to the reaction solution to carry out a liquid separation treatment.
  • the ethyl acetate phase was recovered, dried using sodium sulfate (Fuji Film Wako Pure Chemical Industries) as the desiccant, filtered, and the filtrate was concentrated to obtain an oily substance.
  • Silica gel column chromatography manufactured by Kanto Chemical Co., Inc. was purified using hexane and ethyl acetate (the ratio of hexane and ethyl acetate was changed from 10: 1 to 1: 1), and 4.1 mg of oleocanthal (yield) 63%).
  • Example 10 ⁇ Production of loganine-derived glutaraldehyde compound by solid acid catalyst> Loganin (purchased from ChengduBiopurify) 10 mg in a 2 mL glass tube, Bentonite (Kunimine Industries Kunipia F, H + substitution type) 20 mg as a solid acid catalyst, 0.5 mL of dimethyl sulfoxide as an organic solvent (1.36 mg of water) Content, measured by Karl Fischer titration method), and allowed to stand at 150 ° C. in an oil bath. After 12 hours, 10 mL of pure water and 10 mL of ethyl acetate (Kishida Chemical) were added to the reaction solution to carry out a liquid separation treatment.
  • Loganin purchased from ChengduBiopurify
  • Bentonite Korean Industries Kunipia F, H + substitution type
  • the ethyl acetate phase was recovered, dried using sodium sulfate (Fuji Film Wako Pure Chemical Industries) as the desiccant, filtered, and the filtrate was concentrated to obtain an oily substance.
  • Silica gel column chromatography manufactured by Kanto Chemical was purified using hexane and ethyl acetate (the ratio of hexane and ethyl acetate was changed from 10: 1 to 1: 1), and 1.1 mg of loganine-derived glutaraldehyde compound was obtained. (Yield 25%) was obtained.
  • Example 11 ⁇ Production of oleacein using oleuropein isolated from olive leaf by solid acid catalyst> To an Erlenmeyer flask with an internal volume of 100 mL, 10 g of olive leaf (purchased from Hinata Foods Co., Ltd.) and 40 mL of an 80% methanol solution were added, and the mixture was left at room temperature for extraction. After 12 hours, olive leaves were removed by filtration, and the filtrate was concentrated to obtain an oily substance.
  • the ethyl acetate phase was recovered, dried using sodium sulfate (Fuji Film Wako Pure Chemical Industries) as the desiccant, filtered, and the filtrate was concentrated to obtain an oily substance.
  • Silica gel column chromatography (silica gel manufactured by Kanto Chemical Co., Inc.) was purified using hexane and ethyl acetate (the ratio of hexane and ethyl acetate was changed from 10: 1 to 1: 1), and 598 mg of oleacein (75% yield). %)Obtained.
  • Example 3-3 the reaction was performed in the same manner as in Example 3-3 except that 1000 molar equivalents of water was added to oleuropein. No oleacein was formed, and no oleuropein residue was observed. It was. Therefore, control of the amount of moisture is important in the present invention.
  • the present invention is useful for producing a corresponding glutaraldehyde derivative in high yield using a naturally occurring iridoid compound as a raw material.
  • the manufactured glutaraldehyde derivative can be provided as a pharmaceutical, a pharmaceutical raw material, or a functional food.

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Abstract

L'invention concerne un procédé de production relativement efficace d'un dérivé de glutaraldéhyde à l'aide d'un composé iridoïde présent dans la nature sous forme de matière première, ledit dérivé de glutaraldéhyde contenant un substituant qui est fixé au cycle pyrane dans le composé iridoïde de départ. Le procédé de production d'un dérivé de glutaraldéhyde à l'aide d'un composé iridoïde présent dans la nature sous forme de matière première, ledit dérivé de glutaraldéhyde contenant au moins une structure de substituant qui est fixée au cycle pyrane dans le composé iridoïde de départ, est caractérisé en ce qu'il comprend l'utilisation en tant que catalyseur d'un acide solide ou d'un acide liquide ayant un pKa de 5 ou moins. Le catalyseur acide solide est au moins un élément choisi parmi l'alumine de silice, la zéolite, la zircone sulfatée, la bentonite et l'acide sulfonique de polystyrène.
PCT/JP2019/003098 2018-02-02 2019-01-30 Procédé de production d'un dérivé de glutaraldéhyde provenant d'un matériau naturel WO2019151299A1 (fr)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008136037A2 (fr) * 2007-05-04 2008-11-13 Università Degli Studi Magna Graecia Di Catanzaro Procédé chimico-catalytique pour la péracylation de l'oléuropéine et de ses produits d'hydrolyse
JP2013216628A (ja) * 2012-04-11 2013-10-24 Suntory Holdings Ltd 概日リズム調整剤

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008136037A2 (fr) * 2007-05-04 2008-11-13 Università Degli Studi Magna Graecia Di Catanzaro Procédé chimico-catalytique pour la péracylation de l'oléuropéine et de ses produits d'hydrolyse
JP2013216628A (ja) * 2012-04-11 2013-10-24 Suntory Holdings Ltd 概日リズム調整剤

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