• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Enzymatic synthesis procedure of monoesters of polyhydroxy compounds. The present invention relates to a method of enzymatic synthesis of monoesters of polyhydroxy compounds, being able to isolate and obtain the monoester product in high yield, without mixtures of other possible esters such as, for example, bi-esters or tri-esters. The process is carried out in means free of organic solvents. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2735636A1
    申请号:ES201830595
    申请日:2018-06-19
    公开日:2019-12-19
    发明作者:Rodríguez Pedro Lozano；González Elena Alvarez；Palazón Juana María Bernal；Cerón Susana Nieto；García Celia Gómez；González Antonio Donaire
    申请人:Universidad de Murcia；
    IPC主号:
    专利说明:

    [0001]
    [0002] Enzymatic synthesis procedure of monoesters of polyhydroxy compounds
    [0003]
    [0004] The present invention relates to a method of enzymatic synthesis of monoesters of polyhydroxy compounds, the monoster product being able to be isolated and obtained with high yield, without mixtures of other possible esters such as, for example, bi-esters or tri-esters. The process is carried out in means free of organic solvents.
    [0005]
    [0006] Background of the invention
    [0007]
    [0008] The esters of polyhydroxylated compounds (i.e. panthenol,) are bioactive products of widespread application in the cosmetic and pharmaceutical industries, with panthenyl triacetate being the most commonly used product. The esters are currently obtained by chemical or enzymatic catalysis from derivatives of the carboxylic acids (eg acyl chlorides, vinyl esters, acetic anhydride, etc.), in reaction media based on organic solvents.
    [0009]
    [0010] For example, panthenyl triacetate is synthesized chemically, by means of, for example, a mixture of dimethyl aminopyridine and anhydrous acetic acid as a catalyst, and using temperatures of up to 110 ° C, and successive stages of purification, which implies a cost in its manufacture as described in the patent with publication number US6982346.
    [0011]
    [0012] In other cases, the acylation reaction of panthenol by acetic anhydride is catalyzed by strong acids, such as p-toluenesulfonyl as described in the patent with application number CN201611254844. In any case, these classic organic synthesis processes are not very selective, since they do not allow obtaining mono- or diester derivatives, because the extent of the acylation reaction occurs without control. Furthermore, as a consequence of the use of soluble acids or bases as catalysts, it can generate the appearance of unwanted products, given the exothermic nature of the reactions, and the poor selectivity of the catalysts. Therefore, a purification stage that increases production costs is necessary, in addition to generating residual products that negatively affect the sustainability and / or "green" character of production processes, as contemplated in the principles of Green Chemistry
    [0013]
    [0014] Enzymatic catalysis is the most selective synthesis strategy for the synthesis of chemical products, being one of the pillars in the development of Green Chemistry and / or Sustainable Chemistry.
    [0015]
    [0016] The enzymatic synthesis of panthenol monoesters by transesterification reactions has been carried out using various acyl esters as an acyl donor substrate, e.g. ex. methyl acrylate, methyl methyl acrylate, etc., and panthenol, as described in patent application WO2008053051. In addition, the presence of two primary hydroxyl groups in panthenol determines the uncontrolled obtaining of panthenol diesters as a result of two consecutive catalytic processes on the same panthenol molecule. The use of carboxylic acid derivatives as acyl donors in transesterification reactions (eg vinyl esters, isopropenyl esters, alkyl esters, anhydrides, etc.), not only entails an increase in processes against the use of fatty acids. free, but also a considerable loss of sustainability of the processes, since said compounds are necessary to obtain them by chemical synthesis from the free carboxylic acids, which results in a consumption of reagents and solvents.
    [0017]
    [0018] In all the cases described, the enzymatic synthesis of monoesters of hydroxylated compounds by transesterification reactions, has been carried out in reaction media containing organic solvents, generally aprotic (eg acetonitrile, tetrahydrofuran, acetone, etc.) in order to allow the dissolution of both substrates, panthenol and the acyl donor esters, and thus be able to obtain a single-phase liquid system, where chemical reactions can be verified.
    [0019]
    [0020] Both substrates, panthenol and esters of carboxylic acids, have clearly contrasted solvent properties, since the hydrophilic and hygroscopic character of panthenol contrasts with the hydrophobic and water-insoluble character of the esters of the acyl donors used. These characteristics determine that it is necessary to use organic solvents of intermediate polarity to achieve solubilization of the reactants.
    [0021]
    [0022] In addition, after the catalytic reaction, it is necessary to remove any trace of the organic solvent used, as well as the secondary products of the reaction (eg methanol, acetaldehyde, etc.), for the recovery and use of the corresponding panthenyl monoester for the preparation of any consumer product.
    [0023] For all the above, it would be very interesting to be able to develop a process of synthesis of monoesters of hydroxylated compounds by direct esterification between a free carboxylic acid and an alcohol without organic solvents and in the presence of water and without the use of derivatized / functionalized substrates, in order to allow the preparation of monophasic / homogeneous reaction media, as well as the improvement in the yields of the obtained monoesters.
    [0024]
    [0025] Description of the invention
    [0026]
    [0027] The present invention describes the process of selective enzymatic synthesis of monoesters of polyhydroxy compounds, said synthesis being verified by direct esterification between free carboxylic acids and the polyhydroxy compound, and without the use of any type of derivatization and / or chemical functionalization in both molecules / substrates, and without using any volatile organic solvent in the process.
    [0028]
    [0029] The present invention relates to a method of enzymatic synthesis of monoesters of polyhydroxy compounds, comprising the steps of:
    [0030] a) Form a monophasic eutectic mixture by mixing and melting by heating, in the presence of water of a carboxylic acid of formula R 1 -COOH where R 1 is an aliphatic radical of 10 to 25 carbon atoms, which can be saturated or unsaturated with a polyhydroxy compound of formula R 2 -OH or R 3 CONHR 4 -OH
    [0031] where R 2 is a three to 20 carbon aliphatic radical containing at least two free hydroxyl groups and may be substituted in any of the C of the aliphatic radical with a linear or branched (C 1 -C 3 ) alkyl;
    [0032] and where R 3 CONHR 4 -OH contain at least two free hydroxyl groups and where R 3 and R 4 can be the same or different and are an aliphatic radical of three to 10 carbons that can be substituted at any of the C of the aliphatic radical with a linear or branched (C 1 -C 3 ) alkyl;
    [0033] b) add a hydrolytic enzyme (EC3.1) to the mixture of step a) at a temperature between 30 ° C and 100 ° C for the formation of the corresponding monoster and remove the H 2 O as formed in the reaction.
    [0034]
    [0035] In the present invention in step a) both substrates are mixed, with heating in order to produce the fusion of all solid substrates. Preferably the mixing is carried out with continuous stirring, more preferably mechanical, or magnetic stirring so that a liquid and single phase eutectic mixture is generated. Said liquid mixture generated after the fusion is free of all types of volatile organic solvent, and is presented as a single homogeneous, colorless and transparent liquid phase, presenting a certain gel character, and which is stable at temperatures between 20 ° C and 90 ° C for periods of time longer than one week.
    [0036]
    [0037] In the present invention, as acyl donor substrates, free fatty acids of the formula R and -COOH are used. Preferably R i has between 2 and 18 carbon atoms, more preferably between 10 and 18 carbon atoms. Even more preferably it is selected from: decanoic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid or linolenic acid, among others, used without any modification and / or chemical derivatization on its carboxylic functional group.
    [0038]
    [0039] In the present invention, preferably the polyhydroxy compound of formula R 2 -OH or R 3 CONHR 4 OH is understood to cover substances having at least two esterifiable hydroxyl groups independently of any carboxylic group that may be in the same molecule. Preferably the polyhydroxy compound of formula R 2 -OH or R 3 CONHR 4 has three, four, five or six free hydroxyl groups. Preferably R 2 is a four to 10 carbon aliphatic radical containing four, five or six free hydroxyl groups.
    [0040]
    [0041] More preferably the polyhydroxy compound of formula R 2 -OH or R 3 CONHR 4 -OH is selected from panthenol, xylitol and sorbitol. In particular, R 3 CONHR 4 -OH is panthenol. Panthenol, both in its enantiomer D, and the racemic mixture D, L, being used without any chemical modification on its hydroxyl functional groups. In particular, R 2 -OH is selected from xylitol and sorbitol.
    [0042]
    [0043] In the present invention, preferably hydrolytic enzymes are selected from esterases (EC3.1.1.), Lipases (EC3.1.1.3) and proteases (EC3.4.) They may be either free or immobilized on solid supports (eg Lewatit, polystyrene, etc). For the present invention, some particularly representative examples are: Candida antarctica lipase A (CALA), Candida antarctica lipase B (CALB), Alkalygenes sp. Lipases, Aspergillus sp. Mucor sp., Geotricum sp., Ricopus sp., Burkholderia sp., Candida sp., Candida cylinderracea, Thermomices lanuginous, Mucor mihei, Rizomucor mihei, Pseudomonas fluorescens, Mucor javanicus, or lipasas of pig panceras, both in their free form , as immobilized on solid supports (eg Lewatit, polystyrene, etc.), some marketed under the brand Novozyme® 868, Novozyme® 525L, Novozyme® 435, Novozyme® 388, Lypozyme® RM, Novozyme® 871 and Lypozyme® TL. In particular, lipase is Candida antarctica.
    [0044]
    [0045] In the present invention, it is especially desirable to use free Candida antarctica lipase (CALB) (Novozym® 525 L), or adsorption immobilized Candida Bipa lipase B on Lewatit WO No. 89/02916 (Novozym® 435).
    [0046]
    [0047] The polyhydroxy compound and the carboxylic acid are in any molar ratio, it being preferable to use a molar ratio between the carboxylic acid and the polyhydroxy compound of 1: 1 (mol: mol), it being especially favorable to employ a molar ratio between the carboxylic acid and the 1: 2 polyhydroxy compound (mol: mol).
    [0048]
    [0049] Preferably the amount of water in step a) is comprised between 0.1 and 20% (weight / weight) with respect to the content by weight of the polyhydroxy compound, with an amount of water between 0.1% and 10% (weight / weight) of the hydroxylated compound, and especially recommended an amount of water equivalent to 0.5% (weight / weight).
    [0050]
    [0051] Preferably step a) is carried out at a temperature between 60 ° C and 200 ° C. Preferably step a) is carried out within a reactor with agitation and capacity to perform vacuum. The corresponding amounts of both substrates, carboxylic acid and hydroxylated compound in the desired molar ratio, as well as the amount of water required, will be mixed in the reactor. The system will close tightly and a vacuum pressure of -1 bar will be applied, and it will be kept under constant agitation (orbital, mechanically or magnetically) at a temperature between 60 ° C and 200 ° C, a temperature between 70 being preferable ° C and 150 ° C, a temperature of 100 ° C being especially favorable. Step a) is preferably performed for a time between 30 min and 24 h, a time between 1 and 2 hours being preferable.
    [0052]
    [0053] Preferably, step a) may be heated with microwave irradiation at a power between 300-900 watts. Preferably for a time between 1 30 min, microwave heating at a power of 600 watts for 1-2 min is preferable.
    [0054]
    [0055] Step b) is preferably carried out at a temperature between 40 ° C and 80 ° C, and more favorably at 75 ° C for at least one hour.
    [0056]
    [0057] In the present invention, and since in the esterification reaction catalyzed by the enzyme water is released as a byproduct thereof, preferably in step b) the removal of water is carried out by hygroscopic molecular sieves, which act as desiccants, in order to ensure that the process is carried out under anhydrous conditions, and thus favor the synthesis reaction by improving the yields of the product obtained.
    [0058]
    [0059] Preferably in step b) an amount of drying agent and / or molecular sieve between 5 and 50% (weight / weight) with respect to the weight of the reaction eutectic mixture will be added, with an amount of drying agent being preferred between 10 and 30%, and particularly favorable the addition of 15% (weight / weight) of desiccant agent, with respect to the total mass of the substrates.
    [0060]
    [0061] Preferably step b) where the amount of eutectic substrate mix is present, together with the desiccant agent and the immobilized enzyme, must be maintained under mechanical or magnetic stirring (100-500 rpm), for a time between 1 h and 72 h, a time between 6 h and 24 h being preferred.
    [0062]
    [0063] Examples
    [0064]
    [0065] EXAMPLE OF REALIZATION
    [0066]
    [0067] The following examples illustrate, but do not limit, the present invention.
    [0068]
    [0069] Example 1. Example of enzymatic synthesis of panthenyl monodecanoate in the absence of solvent
    [0070]
    [0071] In an eppendorf® tube of 2 mL capacity, 0.2 grams of decanoic acid, 0.5 g of panthenol and 0.05 grams of water are added, the resulting mixture is heated at 70 ° C until they are completely melted. Subsequently, 0.08 grams of desiccant, molecular sieves MS 13-X (Sigma) are added and the mixture is conditioned at a temperature of 45 ° C for 30 minutes.
    [0072] Finally, 0.08 grams of biocatalyst, Novozyme® 435 are added, starting the synthesis reaction, keeping the reaction vial at 45 ° C by applying pulses of 45-second ultrasound, with an amplitude of 70. After one hour of reaction, the mixture is filtered through a 0.45 micron membrane to separate the solid fraction, and the resulting liquid fraction is analyzed by CG-FID. The yield and selectivity of the synthesis process of panthenyl monodecanoate is determined, obtaining the following results:
    [0073]
    [0074] Yield (%): 69.90
    [0075] Selectivity (%): 92.40
    [0076]
    [0077] Example 2. Example of enzymatic synthesis of panthenyl monolaurate in the absence of solvent
    [0078]
    [0079] In a 100 mL flask 34 grams of Panthenol, 17 grams of lauric acid and 0.2 grams of water are added, the resulting mixture is heated at 75 ° C until they are completely melted. Subsequently, 3.5 g of molecular drying agent MS 13-X (Sigma) are added and the mixture is conditioned at a temperature of 60 ° C for 3 h. Finally, 3.5 g of biocatalyst, Novozyme® 435 are added, starting the synthesis reaction, keeping the flask under constant agitation of 250 rpm and at a temperature of 60 ° C. After six hours of reaction, the mixture is filtered through a 0.45 micron membrane to separate the solid fraction, and the resulting liquid fraction is analyzed by CG-FID. The yield and selectivity of the synthesis process of panthenyl monolaurate is determined, obtaining the following results:
    [0080]
    [0081] Yield (%): 80.93
    [0082] Selectivity (%): 96.99
    [0083]
    [0084] Example 3. Example of enzymatic synthesis of panthenyl monooleate in the absence of solvent
    [0085]
    [0086] In a 4 mL vial, 0.4 grams of Panthenol, 117 pL of oleic acid and 0.02 grams of water are added, the resulting mixture is kept under microwave irradiation at 600 watts for 2 minutes.
    [0087]
    [0088] Subsequently, 0.6 g of molecular drying agent MS 13-X (Sigma) is added and the mixture is conditioned at a temperature of 60 ° C for 15 minutes. Finally, 0.60 g of biocatalyst, Novozyme® 435 are added, starting the synthesis reaction, keeping the vial at a temperature of 60 ° C ultrasound pulses of 45 seconds duration. After 2 hours of reaction, the mixture is filtered through a 0.45 micron membrane to separate the solid fraction, and the resulting liquid fraction is analyzed by CG-FID. The yield and selectivity of the synthesis process of panthenyl monooleate is determined by obtaining the following results:
    [0089]
    [0090] Yield (%): 87.41
    [0091] Selectivity (%): 99.49
    [0092]
    [0093] Example 4. Example of enzymatic synthesis of panthenyl monopalmitate in the absence of solvent
    [0094]
    [0095] In a 4 mL vial, 0.4 grams of Panthenol, 0.170 grams of palmitic acid and 0.02 grams of water are added. The resulting mixture is kept under microwave irradiation at 600 watts for 2 minutes. Subsequently, 0.6 grams of MS-13X (Sigma) desiccant agent are added and conditioned at a temperature of 60 ° C for 30 minutes. Finally, 0.02 grams of biocatalyst, Novozyme® 435 are added, starting the synthesis reaction, keeping the flask under constant agitation of 250 rpm and at a temperature of 60 ° C. After six hours of reaction, the mixture is filtered through a 0.45 micron membrane to separate the solid fraction, and the resulting liquid fraction is analyzed by CG-FID. The yield and selectivity of the synthesis process of panthenyl monopalmitate is determined by obtaining the following results:
    [0096]
    [0097] Yield (%): 85.93
    [0098] Selectivity (%): 99.00
    [0099]
    [0100] Example 5. Example of enzymatic synthesis of panthenyl monodecanoate in the absence of solvent
    [0101]
    [0102] In a 50 mL flask 1130 grams of decanoic acid, 13.50 grams of Panthenol and 0.1 grams of water are added, the resulting mixture is heated at 70 ° C until they are completely melted. Subsequently, 2.30 grams of molecular desiccant are added, MS 13-X (Sigma) and the mixture is conditioned at a temperature of 60 ° C for 2 h. Finally 2.6 grams of biocatalyst, Novozyme® 435 are added, starting the synthesis reaction. The reaction takes place in a tightly sealed reactor, with a pressure of - 1 bar and is kept under constant stirring of 250 rpm and 60 ° C. Passed Six hours of reaction, the mixture is filtered through a 0.45 micron membrane to separate the solid fraction, and the resulting liquid fraction is analyzed by CG-FID. The yield and selectivity of the synthesis process of panthenyl monodecanoate is determined by obtaining the following results:
    [0103]
    [0104] Yield (%): 71.82
    [0105] Selectivity (%): 96.10
    [0106]
    [0107] Example 6. Example of enzymatic synthesis of panthenyl monomiristate in the absence of solvent
    [0108]
    [0109] In a 4 mL vial, 0.42 grams of Panthenol, 0.23 grams of myristic acid and 0.01 grams of water are added. The resulting mixture is heated at 70 ° C until they are completely melted. Subsequently, 0.50 grams of drying agent (molecular sieves MS 13-X, Sigma) are added and the mixture is conditioned at a temperature of 60 ° C for 30 minutes. Finally, 0.50 grams of biocatalyst, Novozyme® 435 are added, starting the synthesis reaction. The reaction takes place in a tightly sealed reactor, with a pressure of - 1 bar and is kept under constant stirring of 250 rpm and 60 ° C. After six hours of reaction, the mixture is filtered through a 0.45 micron membrane to separate the solid fraction, and the resulting liquid fraction is analyzed by CG-FID. The yield and selectivity of the synthesis process of panthenyl monomiristate is determined by obtaining the following results:
    [0110]
    [0111] Yield (%): 82.27
    [0112] Selectivity (%): 93.90
    [0113]
    [0114] Example 7. Example of enzymatic synthesis of panthenyl monooleate in the absence of solvent
    [0115]
    [0116] In a 4 mL vial, 0.42 grams of Panthenol, 0.71 mL of oleic acid and 0.02 grams of water are added. The resulting mixture is melted by irradiating microwaves at 400 watts, until they are completely melted. Next, 0.80 grams of molecular desiccant are added to MS 13-X (Sigma) and the mixture is conditioned at 60 ° C and 250 rpm for 30 minutes. Finally, 0.80 grams of biocatalyst, Novozyme® 435 are added, starting the synthesis reaction. The reaction takes place, in a temperature reactor constant of 60 ° C and 250 rpm. After six hours of reaction, the mixture is filtered through a 0.45 micron membrane to separate the solid fraction, and the resulting liquid fraction is analyzed by HPLC-DAD. The yield and selectivity of the synthesis process of panthenyl monooleate is determined, obtaining the following results:
    [0117]
    [0118] Yield (%): 60.43
    [0119] Selectivity (%): 99.22
    [0120]
    [0121] Example 8. Example of enzymatic synthesis of xylitol monolaurate in the absence of solvent
    [0122]
    [0123] In a 25 mL flask, 3 grams of xylitol, 8 grams of lauric acid and 0.06 grams of water are added. The resulting solid mixture is heated at 85 ° C until the substrates are completely melted. Subsequently, 0.6 g of molecular drying agent MS 13-X (Sigma) is added and the mixture is conditioned at a temperature of 60 ° C for 12 h. Finally, 0.6 g of biocatalyst, Novozyme® 435 are added, starting the synthesis reaction, keeping the flask under constant agitation of 250 rpm and at a temperature of 60 ° C. After twelve hours of reaction, the mixture is filtered through a 0.45 micron membrane to separate the solid fraction (enzyme and molecular sieves), and the resulting liquid fraction is analyzed by HPLC-DAD. The retention times of substrates and products are:
    [0124] Xylitol: 2.1 min; lauric acid: 10.6 min; xylitol monolaurate: 6.5 min; Xylitol dilaurate: 19.6 min
    [0125] The yield and selectivity of the xylitol monolaurate synthesis process is determined by obtaining the following results:
    [0126]
    [0127] Yield (%): 90%
    [0128] Selectivity (%): 60%
    [0129]
    [0130] Example 9: Example of enzymatic synthesis of sorbitol monolauarate in the absence of solvent
    [0131]
    [0132] In a 25 mL flask 3.7 grams of sorbitol, 8 grams of lauric acid and 0.11 grams of water are added. The resulting solid mixture is heated at 95 ° C until the substrates are completely melted. Subsequently, 0.74 g of molecular desiccant agent are added after MS 13-X (Sigma) and the mixture is conditioned at a temperature of 60 ° C for 12 h. Finally, 0.74 g of biocatalyst, Novozyme® 435 are added, starting the Synthesis reaction, keeping the flask under constant agitation of 250 rpm and at a temperature of 60 ° C. After twelve hours of reaction, the mixture is filtered through a 0.45 micron membrane to separate the solid fraction (enzyme and molecular sieves), and the resulting liquid fraction is analyzed by HPLC-DAD. The retention times of substrates and products are:
    [0133] Sorbitol: 2.4 min; lauric acid: 10.6 min; sorbitol monolaurate: 7.0: sorbitol dilaurate: 20.2 min
    [0134] The yield and selectivity of the sorbitol monolaurate synthesis process is determined by obtaining the following results:
    [0135]
    [0136] Yield (%): 60.4
    [0137] Selectivity (%): 61.0
    权利要求:
    Claims (11)
    [1]
    1. Enzymatic synthesis process of monoesters of polyhydroxy compounds, characterized in that the steps of:
    a) Form a monophasic eutectic mixture by mixing and melting by heating, in the presence of water of a carboxylic acid of formula R1-COOH where R1 is an aliphatic radical of 10 to 25 carbon atoms, which can be saturated or unsaturated with a polyhydroxy compound of formula R2-OH or R3CONHR4-OH
    where R2 is a three to 20 carbon aliphatic radical containing at least two free hydroxyl groups and may be substituted in any of the C of the aliphatic radical with a linear or branched (C1-C3) alkyl;
    and where R3CONHR4-OH contains at least two free hydroxyl groups and where R3 and R4 can be the same or different and are an aliphatic radical of three to 10 carbons that can be substituted in any of the C of the aliphatic radical with an alkyl (C1- C3) linear or branched;
    b) add a hydrolytic enzyme (EC3.1) to the mixture of step a) at a temperature between 30 ° C and 100 ° C for the formation of the corresponding monoster and remove the H2O as formed in the reaction.
    [2]
    2. Synthesis process according to claim 1 characterized in that step a) is carried out at a temperature between 60 ° C and 200 ° C.
    [3]
    3. Synthesis method according to any one of claims 1 to 2 characterized in that the hydrolytic enzyme (EC3.1.) Is selected from: esterases (EC3.1.1.), Lipases (EC3.1.1.3.) And proteases (EC3.4.).
    [4]
    4. Synthesis method according to claim 3 characterized in that the lipase is Candida Antarctica.
    [5]
    5. Synthesis process according to any one of claims 1-4 characterized in that the carboxylic acid of formula R1-COOH is selected from: decanoic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, acid linoleic and linolenic acid.
    [6]
    6. Synthesis process according to any one of claims 1-5 characterized in that the polyhydroxy compound of formula R2-OH is selected from xylitol and sorbitol.
    [7]
    7. Synthesis method according to any one of claims 1-5 characterized because the polyhydroxy compound of formula R 3 CONHR 4 -OH is panthenol.
    [8]
    8. Synthesis process according to any one of claims 1-7 characterized in that the removal of H 2 O as formed in step b) is carried out by hygroscopic molecular sieves.
    [9]
    9. Synthesis process according to any one of claims 1-8 characterized in that step a) is carried out in a reactor with agitation and capacity to perform vacuum.
    [10]
    10. Synthesis method according to any one of claims 1-9 characterized in that step a) is carried out for a time between 1 hour and 2 hours.
    [11]
    11. Synthesis method according to any one of claims 1-10, characterized in that in step a) the fusion is carried out by microwave irradiation at a power between 300-900 watts, for a time between 1-30 min.
    类似技术:
    公开号 | 公开日 | 专利标题
    Ortiz et al.2019|Novozym 435: the “perfect” lipase immobilized biocatalyst?
    ES2373171T3|2012-02-01|IMMOBILIZED INTERFACE ENZYMES OF IMPROVED AND STABILIZED ACTIVITY.
    ES2447540T3|2014-03-12|Modified enzymes immobilized with high tolerance against hydrophilic substrates in organic media
    KR20100098421A|2010-09-06|A robust multi-enzyme preparation for the synthesis of fatty acid alkyl ester
    JP2020513750A|2020-05-21|Enzymatic enrichment of n-3 fatty acids in the form of glycerides
    JP2005287510A|2005-10-20|Method for enzymatically synthesizing triglyceride of unsaturated fatty acid
    Bezbradica et al.2017|Enzymatic syntheses of esters-green chemistry for valuable food, fuel and fine chemicals
    CN103952448B|2016-04-27|A kind of method utilizing enzyme-chemically method directional preparation OPO
    Wang et al.2009|A simple procedure for the synthesis of potential 6-azauridine prodrugs by Thermomyces lanuginosus lipase
    US5508182A|1996-04-16|Esterification of hydrophilic polyols by adsorption onto a solid support and employing a substrate-immiscible solvent
    ES2735636B2|2020-04-22|Enzymatic synthesis procedure of monoesters of polyhydroxy compounds
    Sebrão et al.2011|Regioselective acylation of d-ribono-1, 4-lactone catalyzed by lipases
    Osuna et al.2012|Study of the influence of microwave and conventional heating on the lipase-catalyzed esterification of lauric acid with different alcohols
    WO2009130880A1|2009-10-29|Method for production of immobilized enzyme
    Wongsakul et al.2004|Lipase‐catalyzed synthesis of structured triacylglycerides from 1, 3‐diacylglycerides
    WO2008009772A1|2008-01-24|Method for producing biodiesel using porcine pancreatic lipase as an enzymatic biocatalyst
    ES2343773B1|2011-06-24|ENZYMATIC PROCEDURE FOR ACILATION IN POSITION 3- OF RESVERATROL.
    Wei et al.2003|Enzymatic esterification for glycoside lactate synthesis in organic solvent
    ES2324368T3|2009-08-05|PROCEDURE FOR THE ENZYMATIC SYNTHESIS OF TRIGLICERIDS.
    JP3813585B2|2006-08-23|Method for producing diglyceride
    ES2300197B1|2009-05-01|PROCEDURE OF OBTAINING POLYGYRICOLOLATE POLYGYLEROLATE.
    Kim et al.2016|Production of Omega-3 fatty acid ethyl esters from menhaden oil using Proteus vulgaris lipase-mediated one-step transesterification and urea complexation
    JP3813584B2|2006-08-23|Method for producing diglyceride
    JP5586855B2|2014-09-10|Method for producing monoacylglycerol-rich oil and fat
    WO1992014830A1|1992-09-03|Enzymatic reverse hydrolysis of hydrophilic substrates - preparation of amphiphilic compounds
    同族专利:
    公开号 | 公开日
    WO2019243656A1|2019-12-26|
    ES2735636B2|2020-04-22|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    WO2008053051A2|2006-12-15|2008-05-08|Haering Dietmar|Panthenol esters of unsaturated carboxylic acids|
    CN103114108A|2012-09-03|2013-05-22|常州大学|Method for preparing D-panthenol 16 ether monopalmitate by using lipase as catalyst|
    法律状态:
    2019-12-19| BA2A| Patent application published|Ref document number: 2735636 Country of ref document: ES Kind code of ref document: A1 Effective date: 20191219 |
    2020-04-22| FG2A| Definitive protection|Ref document number: 2735636 Country of ref document: ES Kind code of ref document: B2 Effective date: 20200422 |
    优先权:
    申请号 | 申请日 | 专利标题
    ES201830595A|ES2735636B2|2018-06-19|2018-06-19|Enzymatic synthesis procedure of monoesters of polyhydroxy compounds|ES201830595A| ES2735636B2|2018-06-19|2018-06-19|Enzymatic synthesis procedure of monoesters of polyhydroxy compounds|
    PCT/ES2019/070493| WO2019243656A1|2018-06-19|2019-07-15|Method for enzymatic synthesis of monoesters of polyhydroxylated compounds|
    [返回顶部]