EP1567655A2 - Production enzymatique de derives de flavonoides acyles - Google Patents

Production enzymatique de derives de flavonoides acyles

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Publication number
EP1567655A2
EP1567655A2 EP03812154A EP03812154A EP1567655A2 EP 1567655 A2 EP1567655 A2 EP 1567655A2 EP 03812154 A EP03812154 A EP 03812154A EP 03812154 A EP03812154 A EP 03812154A EP 1567655 A2 EP1567655 A2 EP 1567655A2
Authority
EP
European Patent Office
Prior art keywords
acid
flavonoid
reaction
acyl donor
solvent
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP03812154A
Other languages
German (de)
English (en)
Inventor
Mohamed Ghoul
Jean-Marc Engasser
Philippe Moussou
Gilles Pauly
Melika Ardhaoui
Aude Falcimaigne
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF Health and Care Products France SAS
Original Assignee
Cognis France SAS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cognis France SAS filed Critical Cognis France SAS
Priority to EP03812154A priority Critical patent/EP1567655A2/fr
Publication of EP1567655A2 publication Critical patent/EP1567655A2/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/62—Carboxylic acid esters
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/02—Oxygen as only ring hetero atoms
    • C12P17/06—Oxygen as only ring hetero atoms containing a six-membered hetero ring, e.g. fluorescein

Definitions

  • the invention is in the field of phyto- and biochemistry and relates to a process for the enzymatic production of flavonoid derivatives which are used in the food sector, in cosmetics and in pharmaceutical preparations.
  • flavonoids have been well known for many years. By trapping various oxidizing species, they prevent oxidative damage to biomolecules such as DNA, lipids and proteins. In antioxidant assays, some flavonoids are more effective than nitamines C and E. In addition to this main property, several other biological effects have been demonstrated, including inhibiting the action of enzymes and the proliferation of animal cells, viruses and bacteria. They also have an effect on the vascular system and a strong antioxidant capacity.
  • flavonoids Because of their skin-protecting and cleansing properties and their effects against aging, against skin discoloration and on the appearance of the skin, flavonoids have also been used as components of cosmetic or dermopharmaceutical compositions. Furthermore, they affect the mechanical properties of the hair.
  • the anti-oxidant properties of the flavonoids depend on the molecular principle. Studies of the structure-activity relationship have shown that the antioxidant effect on ortho-hydroxylation on ring B of the molecule, the number of free hydroxyl groups, the presence of a double bond between carbon 2 and 3 in ring C and the presence of a hydroxyl group on carbon 3 ( Figure I) is based.
  • Patent WO 09966062 mentions the chemical acylation of flavonoids (quercetin, galangin, (+) - catechin) by fatty acids (lauric acid, butyric acid, acetic acid ...) and a subsequent enzymatic hydrolysis step by means of a Mucor miehei lipase.
  • This invention has the same disadvantages as the patent FR2778663 (US6235294). After the first performed acylation reaction, the products formed are polyacylated.
  • an enzymatic acylation of flavonoids is carried out using various acids (p-chlorophenylacetic acid, stearic acid, 12-hydroxystearic acid, palmitic acid, palmitic acid, Lauric acid, capric acid, 4-hydroxyphenylacetic acid, 5-phenylvaleric acid, cumaric acid, oleic acid, linoleic acid).
  • This patent describes a process in which a high concentration of Candida antarctica (40 g / 1) and, based on the flavonoids, an excess of acyl donor is used. The conversion rate of the substrates is low (10 to 20%).
  • the invention relates to a process for the enzymatic synthesis of flavonoid esters and derivatives, in which a) a reaction medium is prepared comprising an organic solvent, a glycosylated flavonoid or aglyconflavonoid, an acyl group donor and an enzymatic catalyst, b) optionally adding further amounts of flavonoid and / or acyl donor during the reaction and c) purifying the esters thus obtained by separating enzymatic particles and the solvent, characterized in that the concentration of water formed during the reaction and / or alcohol is controlled so that it is kept below 150 mM.
  • the present invention a process for the selective acylation of glycosylated flavonoids and aglyconflavonoids - leads to the improvement of the flavonoid derivatives with regard to their stability and solubility in various preparations, while their antioxidative properties are retained or improved.
  • Another particular advantage achieved by these modified flavonoids is that bifunctional molecules with higher biological effectiveness are formed.
  • this method can achieve a significant improvement in terms of the final concentrations of flavonoid esters, the conversion yields (both for the flavonoids and the acyl donor originally present) and in particular the productivity, while the complicated, elaborate purification operations after synthesis can be reduced.
  • R ' represents a Cl-C4-alkyl group, preferably a Cl-C2-alkyl group.
  • This process is characterized in that the reaction medium is first dewatered is used to remove any water present before the start of the reaction, and the water or alcohol formed during the reaction is removed online.
  • Water and / or alcohol are kept at concentrations which are suitable for the solvents and substrates used, preferably at concentrations below 150 mM, particularly preferably below 100 mM.
  • the process is suitable for a variety of aglycon flavonoids and glycosylated flavonoids, and the conversion yields achieved with this mild enzymatic process are above those obtained so far: in the range of 50 to 99%.
  • the enzymatic synthesis is carried out under milder conditions than the chemical syntheses, avoiding the use of toxic solvents such as pyridine, benzene and THF, high temperatures and the accumulation of by-products such as salts or flavonoid degradation products, which would require additional purification steps.
  • this method can achieve a significant improvement in terms of the final concentrations of flavonoid esters, the conversion yields (for both the flavonoids and the acyl donor originally present) and, in particular, the productivity, while the complicated, expensive purification operations after the Synthesis can be reduced.
  • a difference between the method according to the invention and the known methods of the prior art is the way in which the enzymatic reaction is carried out, which enables considerably higher yields, and the large number of different flavonoids that can be used (both glycosylated forms and aglycon forms) ,
  • the main aim of the invention is to reduce all of the above-mentioned disadvantages of existing acylation methods and to propose a method for the enzymatic synthesis of flavonoid esters which, compared to the known methods mentioned above, offers a significant improvement in terms of the final concentrations of flavonoid esters, the conversion yields (both for the flavonoids as well as the originally existing acyl donor) and in particular the productivity, while the complicated, expensive purification operations after the synthesis are reduced.
  • the invention relates to a process for the enzymatic synthesis of flavonoid esters, which is characterized in that predetermined amounts of a flavonoid (glycosylated forms and aglycon forms) or flavonoid derivative, an acyl group donor, an organic solvent, in a reactor designed for the formation of a reaction medium it can be the acyl donor and introduces an enzymatic catalyst, under conditions in which the reaction medium can first be dried to a water concentration of less than 150 mM, preferably less than 100 mM and in which the concentration of water formed during the reaction and / or alcohol can be kept below a predetermined point of 150 mM, preferably 100 mM.
  • This predetermined point is met by on-line removal of the water and / or alcohol formed by adsorption on molecular sieves, by distillation or by pervaporation.
  • This reaction can be carried out in the batch process or also in the fed-batch process with one or more substrates.
  • the molar ratio of flavonoid to acyl donor can be kept constant during the reaction by means of a suitable substrate addition profile. It is thus possible to control how the composition of the reaction medium develops over time, and thus to direct the enzymatic reaction towards maximum production of mono- or multiacylated compounds and at the same time to limit interfering reactions.
  • the flavonoid esters thus obtained are finally purified by separating at least enzymatic particles (for example by decanting, filtering or centrifuging) and the solvent (for example by evaporation, distillation or membrane filtration).
  • the reaction is carried out according to the invention in such a way that the inhibition or deactivation of the enzyme reaction which is observed in the presence of high concentrations of flavonoids, acyl donors or water accumulations is initially restricted.
  • the substrates can be fed gradually in a controlled manner as the reaction proceeds, thereby avoiding reaching concentrations that would inhibit the enzyme reaction.
  • the reaction can be carried out so that the flavonoid: acyl donor molar ratio of 0.01 to 20, preferably from 0.02 to 10.
  • the flavonoid: acyl donor molar ratio of 0.01 to 20, preferably from 0.02 to 10.
  • the molar ratio can be kept constant during the reaction or can be varied in a controlled manner, so that it runs through a defined variation profile over time, but is nevertheless in the above-mentioned range of values throughout the reaction .
  • the synthesis reaction can be optimized by temporarily or continuously withdrawing at least one component of the reaction medium. The component (s) withdrawn may possibly be returned to the reactor after fractionation.
  • the reaction vessel or the reactor used for carrying out the process according to the invention is preferably provided with devices for controlling the temperature, the water and / or alcohol content and the pressure, with devices for adding reagents and with devices for withdrawing products.
  • the temperature is advantageously set to 20-100 ° C. and the partial pressure above the reaction medium is advantageously set to 10 mbar (10 3 Pa) to 1000 mbar (10 5 Pa), starting from one to a concentration of less than 150 mM , preferably below 100 mM set initial water content, the amount of water and / or alcohol is kept below 150 mM, preferably below 100 mM and the reaction medium is advantageously stirred gently.
  • aglycon flavonoid or glycosylated flavonoid or flavonoid derivative used in the invention can be any compound selected from the group consisting of chalcon, flavon, flavanol, anthocyanin and flavanone, flavonol, coumarin, isoflavones and xanthones.
  • the acyl donor compound is selected from known fatty acids or their methyl, ethyl, propyl or butyl esters.
  • This fatty acid is preferably selected from that of a straight-chain or branched aliphatic acid, saturated, unsaturated or cyclic, having up to 22 carbon atoms, optionally substituted by one or more substituents, from that of hydroxyl, amino, mercapto, halogen and alkyl-SS-alkyl existing Grappe, for example palmitic acid, 16-hydroxyhexadecanoic acid, 12-hydroxystearic acid, 11-mercaptoundecanoic acid, thioctanoic acid or quinic acid, straight-chain or branched aliphatic diacids, saturated or unsaturated, with up to 22 carbon atoms, for example hexadecanedioic acid or azelaic acid, and an aryl aliphatic acid and an aryl aliphatic acid dimeric acid,
  • the reaction can be carried out with the acyl donor as solvent or in a suitable solvent, which can be any organic compound or any mixture of organic compounds in which the selected flavonoids or flavonoid derivatives and acyl donors are wholly or partly solubilized ,
  • the solvent (s) is selected in particular from the following substances: propan-2-ol, butan-2-ol, isobutanol, acetone, propanone, butanone, pentan-2-one, 1,2-ethanediol, 2,3-butanediol , Dioxane, acetonitrile, 2-methylbutan-2-ol, tert-butanol, 2-methylpropanol and 4- Hydroxy-2-methylpentanone, aliphatic hydrocarbons such as heptane, hexane or a mixture of two or more of these solvents.
  • the enzymatic catalyst used must of course effect and promote the transfer of an acyl group from an acyl donor to a flavonoid or flavonoid derivative and is advantageously a protease or lipase, e.g. from Candida antarctica, Rhizomucor miehei, Candida cylindracea, Rhizopus arrhizus, preferably immobilized on a support.
  • a protease or lipase e.g. from Candida antarctica, Rhizomucor miehei, Candida cylindracea, Rhizopus arrhizus, preferably immobilized on a support.
  • the reactor first contains the solvent, the total amount of flavonoids (generally from 1 g / 1 to 200 g / 1) required to obtain the desired final amount of modified flavonoids and the amount of free acid as Acyl donor, which corresponds to the molar ratio (of dissolved flavonoid / acyl donor) originally required (generally from 0.01 to 20).
  • the medium is brought to a temperature of 20-100 ° C., preferably 40-80 ° C.
  • the reactor first contains the solvent, the total amount of flavonoids (in generally from 1 g / 1 to 200 g / 1), which is required to obtain the desired final amount of modified flavonoids, and the amount of free acid as acyl donor, which corresponds to the originally required molar ratio (of dissolved flavonoid / acyl donor) (im generally from 0.01 to 20).
  • the medium is brought under vacuum (10-500 mbar, preferably 50-250 mbar) to a temperature of 20-100 ° C., preferably 40-80 ° C. , heated, and the steam mixture produced is dried in a column filled with molecular sieves and then condensed and returned to the reactor. If necessary, the condensate is led back through a second column filled with molecular sieves. Then the enzyme is added in soluble or immobilized form (from 1 g / 1 to 100 g / 1, preferably from 5 g / 1 to 20 g / 1). During the course of the reaction, solvent is added so that part of the solvent is evaporated off through a column with molecular sieves. The water is removed by exchange in the vapor phase. The steam is condensed and collected in a collecting container.
  • acyl donor is added online in such an amount per unit of time during the reaction that the molar ratio (of dissolved flavonoid / acyl donor) is kept at the required value.
  • the acyl donor is added at a rate which corresponds to the rate of its consumption in the reaction; this rate of consumption can be determined by a preparatory kinetic examination of the enzyme reaction used.
  • the amount of acyl donor added per unit time during the reaction is generally from 0.01 to 10 grams of acyl donor per hour per gram of enzyme catalyst in the reactor.
  • the synthesis process can also be carried out with the addition of flavonoids and solvents.
  • the reactor first contains the solvent, the total amount of free acid as acyl donor (generally from 1 g / 1 to 500 g / 1) required to obtain the desired final amount of modified flavonoids and the amount of Flavonoid, which corresponds to the molar ratio (of dissolved flavonoid acyl donor) originally required (generally from 1 g / 1 to 200 g / 1).
  • the medium is vacuum (10-500 mbar, preferably 50- 250 mbar) to a temperature of 20-100 ° C, preferably 40-80 ° C, and the steam mixture generated is dried in a column filled with molecular sieves and then condensed and returned to the reactor. If necessary, the condensate is recirculated through a second column filled with molecular sieves. Then the enzyme is added in soluble or immobilized form (from 1 g / 1 to 100 g / 1, preferably from 5 g / 1 to 20 g / 1).
  • solvent is added and a vacuum is applied, so that part of the solvent and the water formed are evaporated off.
  • the amount of evaporation is adjusted by controlling the vacuum and the temperature accordingly.
  • the vapors formed are passed over a column filled with molecular sieves.
  • the water is removed by contact with the molecular sieves.
  • the steam is condensed and collected in a collecting tank, in order to be subsequently returned to the reactor.
  • anhydrous solvent is added during the reaction to compensate for evaporation losses and to keep the amount of solvent relatively constant.
  • flavonoid is added in an amount per unit of time such that the molar ratio (of dissolved flavonoid / acyl donor) is kept at the required value.
  • the flavonoid is added at a rate which corresponds to the rate of its consumption in the reaction; this rate of consumption can be determined by a preparatory kinetic examination of the enzyme reaction used.
  • the amount of flavonoid added per unit time during the reaction is generally from 0.01 to 10 grams of flavonoid per hour per gram of enzyme catalyst in the reactor.
  • the synthesis process can also be carried out with the addition of flavonoid, acyl donor and solvent.
  • the reactor first contains the solvent, a variable concentration of flavonoid (preferably higher than the solubility of the flavonoid in the solvent) and the amount of free acid as acyl donor, which corresponds to the molar ratio (of dissolved flavonoid / acyl donor) originally required.
  • the medium is brought under vacuum (10-500 mbar, preferably 50-250 mbar) to a temperature of 20-100 ° C., preferably 40- 80 ° C, heated, and the steam mixture generated is dried in a column filled with molecular sieves and then condensed and returned to the reactor. If necessary, the condensate is returned via a second column filled with molecular sieves. Then the enzyme is added in soluble or immobilized form (from 1 g / 1 to 100 g / 1, preferably from 5 g / 1 to 20 g / 1).
  • solvents are added and a vacuum in the range of 10-500 mbar, preferably 100-250 mbar, is applied.
  • a vacuum in the range of 10-500 mbar, preferably 100-250 mbar.
  • the vapors formed are passed over a column with molecular sieves.
  • the steam is condensed and collected in a collecting container.
  • anhydrous solvent is added during the reaction to compensate for evaporation losses and to keep the amount of solvent relatively constant.
  • flavonoid is added in an amount per unit of time such that the molar ratio (of dissolved flavonoid / acyl donor) is kept at the required value.
  • flavonoid and acyl donor are added in amounts per unit of time, each corresponding to the rate at which they are consumed in the reaction; these consumption rates can be determined by a preparatory kinetic examination of the enzyme reaction used.
  • the continuous synthesis process can alternatively be carried out with the addition and removal of flavonoid, acyl donor and / or solvent and possibly enzyme catalyst.
  • the reactor first contains the solvent, a variable concentration of flavonoid (preferably higher than the solubility of the flavonoid in the solvent) and the amount of free acid as acyl donor, which corresponds to the molar ratio (of dissolved flavonoid / acyl donor) originally required.
  • the medium is brought under vacuum (10-500 mbar, preferably 50-250 mbar) to a temperature of 20-100 ° C., preferably 40-80 ° C.
  • Anhydrous solvent is added during the reaction to compensate for evaporation and stripping losses, and it is still possible to add flavonoid and acyl donor in amounts per unit time to maintain the molar ratio of these two components at the required level.
  • the water is removed through molecular sieves as described above. After dewatering, the evaporated solvent is condensed and returned to the reactor --uriick. If it is advantageous to keep this molar ratio constant during the reaction, flavonoid and acyl donor are added in amounts per unit of time which correspond to their respective consumption rates in the reaction and their respective withdrawal rates.
  • the reaction is carried out as above, but the free acid as acyl donor is replaced by its methyl, ethyl, propyl or butyl ester, preferably its methyl or ethyl ester.
  • the alcohol formed is removed in the same way as above.
  • the acyl donor is used as the solvent.
  • water and / or alcohol present or present in the medium and / or formed during the reaction is removed through a pervaporation membrane, in the vapor or liquid phase.
  • Rutin monopalmitate synthesis was carried out in a 250 ml batch reactor using Candida antarctica lipase (Novozym 435). This is a lipase immobilized on a macroporous acrylic resin. The lipase is supplied with an activity of 7000 PLE xg '1 (propyl laurate synthesis), a water content of 1-2% by weight and an enzymatic protein content in the range between 1 and 10% by weight.
  • PLE xg '1 propyl laurate synthesis
  • a water content of 1-2% by weight a water content of 1-2% by weight
  • an enzymatic protein content in the range between 1 and 10% by weight.
  • 0.75 g (1.2 mmol) of rutin 0.75 g (1.2 mmol) of rutin, 0.315 g (1.2 mmol) of palmitic acid and 250 ml were tert. -Amyl alcohol used. The medium was heated to 60 ° C.
  • This concentration can be varied by adjusting the vacuum and cooling the cooler accordingly.
  • the pressures examined fluctuate between 10 and 700 mbar, and the temperature of the cooler between -20 and 5 ° C. With this procedure it is possible to adjust the water concentration in the reactor to between 5 and 400 mM.
  • the enzyme was recovered by filtration. The medium was then concentrated by evaporating the solvent. Two extraction systems were used to eliminate substrate residues. A mixture of acetonitrile / heptane (3/5, v / v) was used to remove the palmitic acid, while the rutin was separated by extraction with water / heptane (2/3, v / v).
  • HPLC analysis showed that after 48 hours 95% of the acyl donor was used up.
  • the hesperidin monopalmitate could be obtained by liquid-liquid extraction using the same purification instructions as above.
  • the structure of this hesperidin ester was confirmed by 1 H-NMR analysis.
  • Liquid chromatography analysis showed that 80% of the acyl donor was consumed after 48 hours.
  • the same purification instructions as above enabled the esculin monopalmitate to be obtained using liquid-liquid extraction.
  • the structure of this esculin ester was confirmed by 1H NMR analysis.
  • Example 4 An acylation of rutin with lauric acid was carried out in a 27 ml reactor. Rutin (100 mg, 0.16 mmol) and lauric acid (20 mg, 0.10 mol) were in 20 ml of dried tert-amyl alcohol at 60 ° C. solved. A controlled water content in the reaction medium was adjusted to below 100 mM by adding molecular sieves (4 g). The esterification reaction was started by adding 0.2 g of Candida antartica lipase (Novozym 435). The HPLC analysis showed that the conversion of rutin to the monoester was 76%.
  • Rutin (8, 13 mmol) and dodecanedioic acid (0.3 g, 1.3 mmol) were dissolved in 200 ml of tert-amyl alcohol and heated to 60 ° C. under a vacuum of 150-200 mbars). The vapors formed are passed over a column filled with molecular sieves and recovered. In this way, a low water content of less than 100 mm was achieved in the reactor after a few hours. 2 g of Candida antarctica ipase (Novozym 435) were added.
  • the cleaning method of the liquid-liquid extraction according to Example 1 enabled the recovery of hexadecanedioyl rutin (monoester).
  • the structure of the product was confirmed by 1H-NMR analysis.
  • Esculin was reacted with thioctanoic acid in a 250 ml reactor.
  • Esculin (0.87g, 2.5mmol) and thioctanoic acid (1.23g, 6mmol) were dissolved in 250 ml of tert-amyl alcohol and heated to 60 ° C under vacuum (150-200 mbars). The vapors formed are passed over a column filled with molecular sieves and recovered. In this way, a low water content of less than 100 mm was achieved in the reactor after 21 hours. 2.5 g of Candida antarctica lipase (Novozym 435) was added. After 70 hours, 50% of the esculin had been converted (HPLC analysis).
  • the enzyme was filtered and the reaction medium was concentrated by evaporating the solvent.
  • a mixture of water / heptane / acetonitrile (2/3 / 0.4, v / v / v) was used for extraction, and the ester was then obtained by extraction with dichloromethane. The structure of the ester was verified by 1H NMR.

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biotechnology (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

L'invention concerne un procédé de synthèse enzymatique d'ester et de dérivés de flavonoïdes selon lequel : a) on produit un milieu de réaction contenant un solvant organique, un flavonoïde ou un aglyconflavonoïde glycolisé, un donneur de groupes acyle et un catalyseur enzymatique ; b) on additionne, éventuellement, pendant la réaction, d'autres quantités de flavanoïdes et/ou de donneur de groupes acyle ; et c) on purifie les esters ainsi contenus en séparant les particules enzymatiques et le solvant. Ce procédé se caractérise en ce que la concentration en eau et/ou alcool formés pendant la réaction est maîtrisée de façon à être maintenue à une valeur inférieure à 150 mM.
EP03812154A 2002-12-03 2003-11-22 Production enzymatique de derives de flavonoides acyles Withdrawn EP1567655A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP03812154A EP1567655A2 (fr) 2002-12-03 2003-11-22 Production enzymatique de derives de flavonoides acyles

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP02292969A EP1426445A1 (fr) 2002-12-03 2002-12-03 Préparation de dérivés de flavonoides
EP02292969 2002-12-03
PCT/EP2003/013143 WO2004050889A2 (fr) 2002-12-03 2003-11-22 Production de derives de flavonoides
EP03812154A EP1567655A2 (fr) 2002-12-03 2003-11-22 Production enzymatique de derives de flavonoides acyles

Publications (1)

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EP1567655A2 true EP1567655A2 (fr) 2005-08-31

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EP02292969A Withdrawn EP1426445A1 (fr) 2002-12-03 2002-12-03 Préparation de dérivés de flavonoides
EP03812154A Withdrawn EP1567655A2 (fr) 2002-12-03 2003-11-22 Production enzymatique de derives de flavonoides acyles

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Country Status (5)

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US (1) US20060115880A1 (fr)
EP (2) EP1426445A1 (fr)
JP (1) JP2006508654A (fr)
KR (1) KR20050085377A (fr)
WO (1) WO2004050889A2 (fr)

Cited By (1)

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CN110699397A (zh) * 2019-09-26 2020-01-17 湖南华诚生物资源股份有限公司 一种连续酶促酰化花青素的方法

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US20070184098A1 (en) * 2003-06-20 2007-08-09 Philippe Moussou Esters of flavonoids with w-substituted c6-c22 fatty acids
US7807718B2 (en) * 2006-06-30 2010-10-05 Sami A. Hashim Glyceride esters for the treatment of diseases associated with reduced neuronal metabolism of glucose
US7825587B2 (en) * 2006-08-31 2010-11-02 Universal Display Corporation Charge transporting layer for organic electroluminescent device
US20090280429A1 (en) * 2008-05-08 2009-11-12 Xerox Corporation Polyester synthesis
JP2010233566A (ja) * 2009-03-12 2010-10-21 Nisshin Oillio Group Ltd 糖及び／又は糖アルコールのカルボン酸モノエステルの製造方法
CN111304265B (zh) * 2020-02-25 2021-03-02 暨南大学 一种油溶性黑豆皮花色苷酰化产物及其制备方法

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JP3165279B2 (ja) * 1993-03-29 2001-05-14 三井農林株式会社 ３−アシル化カテキンを含有する油溶性抗酸化剤
FR2778663B1 (fr) * 1998-05-15 2001-05-18 Coletica Nouveaux esters de flavonoides,leur utilisation en cosmetique, dermopharmacie, en pharmacie et en agro-alimentaire
US20030170186A1 (en) * 2000-04-18 2003-09-11 Bernadette Geers Novel flavone glycoside derivatives for use in cosmetics, pharmaceuticals and nutrition
DE10019235A1 (de) * 2000-04-18 2001-10-31 Henkel Kgaa Neue Flavonglykosid-Derivate für den Einsatz in Kosmetika, Pharmazeutika und Ernährung

Non-Patent Citations (1)

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Title
See references of WO2004050889A2 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110699397A (zh) * 2019-09-26 2020-01-17 湖南华诚生物资源股份有限公司 一种连续酶促酰化花青素的方法
CN110699397B (zh) * 2019-09-26 2021-06-29 湖南华诚生物资源股份有限公司 一种连续酶促酰化花青素的方法

Also Published As

Publication number Publication date
KR20050085377A (ko) 2005-08-29
EP1426445A1 (fr) 2004-06-09
JP2006508654A (ja) 2006-03-16
WO2004050889A3 (fr) 2004-08-12
US20060115880A1 (en) 2006-06-01
WO2004050889A2 (fr) 2004-06-17

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