Xylitol carboxylic acid esters and enzymatic production thereof

Abstract

The subject of the present invention is xylitol carboxylic acid esters and a method for the enzymatic production of xylitol carboxylic acid esters.

Description

[Technical Field]

[0001] The subject of the present invention is xylitol carboxylic acid esters and a method for the enzymatic production of xylitol carboxylic acid esters.

[0002] prior art Xylitol carboxylic acid esters are important products for the food and cosmetics industry, on the one hand because of their surface-active properties and, on the other hand, because they can be obtained from natural and renewable raw materials.

[0003] EP 2902009 A1 describes the classical chemical esterification of xylitol with fatty acids in the absence of solvents and in the presence of a catalyst such as p-toluenesulfonic acid (pTSA) at temperatures up to 200°C within 8 hours, and the use of the resulting xylitol carboxylic acid esters as active ingredients in cosmetic formulations. The drawback of the classical chemical esterification process is that under these conditions, xylitol always undergoes at least partial dehydration or decomposition (Biotechnol. Bioeng. 1995, 48, 214-221). Three xylitol decomposition products frequently formed under these conditions are the anhydropentitols 1,4-anhydroxylitol, 1,4-anhydroarabinitol, and 1,4-anhydroribitol (J. Carbohydr. Chem. 2004, 23, 4, 169-177 and Adv. Carbohydr. Chem. Biochem. 1983, 41, 27-66). A further drawback of the processes described in the prior art is the use and subsequent removal of activated carbon and terra alba (calcium sulfate) to improve the color and odor of the resulting product.

[0004] Pedersen et al. (Enzyme Microb. Technol. 2007, 41, 3, 346-352) describe the enzymatic synthesis of xylitol carboxylic acid esters using solvents such as tert-butanol and pyridine at a temperature of 45° C. A drawback of this process described in the prior art is that the use of solvents hinders use in the food or cosmetic sector, and furthermore, the necessary solvent removal requires additional process steps such as crystallization, filtration or distillation.

[0005] Basri et al. (Carbohydr. Res. 2011, 346, 472-479) describe the solvent-free esterification of xylitol with both capric and caproic acids using lipase from Candida antarctica at temperatures up to 70°C, optimally 60°C. This process results in a product mixture in which the ratio of esterified primary OH groups to esterified secondary OH groups is always greater than 80:20. A drawback of this process described in the prior art is the use of molecular sieves, which makes it more difficult to implement on an industrial scale. A further drawback of this process described in the prior art is the use of a solvent or solvent mixture to terminate the reaction, remove the enzyme, and remove the molecular sieves. This procedure requires an additional process step to remove the used solvent, eliminating the advantage of a solvent-free process. Another drawback of the process described in the prior art is that tricarboxylic acid esters of xylitol are obtained as the main component with a relative proportion of more than 50% in the ester distribution.Another drawback of the process described in the prior art is that the enzyme loading is unclear.Another drawback of the process described in the prior art is the low conversion rate of only about 70%, and therefore the relatively large amount of fatty acids remaining in the product mixture, about 15%, which then requires fatty acid separation, with prior neutralization if necessary, to avoid unwanted by-products or, for example, in the case of caproic acid, caprylic acid, and capric acid, unpleasant odors.Another drawback of the process described in the prior art is the selectivity for long-chain fatty acids.

[0006] Tan et al. (J. Mol. Catal. B-Enzym 2013, 89, 61-66) described the solvent-free esterification of xylitol with capric acid using lipase (Candida sp. 99-125) at temperatures up to 50°C. From the reported analytical data, it can be inferred that the ratio of esterified primary OH groups to esterified secondary OH groups is always greater than 80:20. A disadvantage of this process described in the prior art is the use of very finely ground xylitol (particle size <0.2 mm), which requires additional process steps and specialized equipment (e.g., Dispermat or specialized mills) for industrial-scale implementation. A further disadvantage of this process described in the prior art is the long reaction time (>100 hours). Another disadvantage of this process described in the prior art is the removal of by-products at temperatures above 140°C, which adversely affects the color of the product. Another disadvantage of this process described in the prior art is the use of enzymes that are not commercially available. A further disadvantage of the process described in the prior art is that the enzyme is not isolated from the wild type. A further disadvantage of the process described in the prior art is the use of a non-immobilized enzyme, which makes handling and separation from the product more difficult from a safety perspective. A further disadvantage of the process described in the prior art is the low recyclability of the lipase used. A further disadvantage of the process described in the prior art is the use of a fed-batch process to avoid high viscosity caused by excess xylitol or capric acid. A further disadvantage of the process described in the prior art is the use of a fed-batch process, which requires special measurement and control techniques. A further disadvantage of the process described in the prior art is the addition of water, which must be removed again at the end of the process.

[0007] Korean Patent No. 101939851 describes the use of the above-mentioned by-products of the classical chemical esterification process for the production of dehydrated xylitol esters, and thus xylitol carboxylic acid esters, as rheological additives / viscosity modifiers in emulsions. The disadvantage of the anhydroxylitol carboxylic acid esters described in the prior art is their reduced hydrophilicity. Another disadvantage of the anhydroxylitol carboxylic acid esters described in the prior art is their dark color. Another disadvantage of such anhydroxylitol carboxylic acid esters is their lack of thickening ability in aqueous surfactant systems.

[0008] The object of the present invention was to provide a process for the preparation of sugar esters and / or sugar alcohol esters, which is able to overcome at least one of the drawbacks of the prior art processes.

[0009] Detailed Description of the Invention Surprisingly, it has been found that the xylitol carboxylic acid esters described below and the methods described below are able to solve the problems set out in the present invention.

[0010] An advantage of the present invention is that the xylitol carboxylic acid esters according to the present invention are superior thickeners for aqueous surfactant systems compared to the prior art.

[0011] A further advantage in this case is that the xylitol carboxylic acid esters according to the invention also have an excellent color and a very good odor compared to the prior art.

[0012] An advantage of the present invention is that only very small amounts of xylitol decomposition products or esters of the decomposition products are obtained as reaction products.

[0013] An advantage of the present invention is that the process according to the invention can be carried out in the absence of a solvent.

[0014] A further advantage of the present invention is that the xylitol carboxylic acid ester is obtained in a homogeneous reaction mixture, so that no additional process steps, such as extraction, crystallization, filtration or distillation, are necessary.

[0015] An advantage of the present invention is that the process can be carried out at high temperatures, which results in improved miscibility of the reaction partners while also providing a surprisingly high recyclability of the enzymes used.

[0016] A further advantage of the present invention is that the resulting xylitol carboxylic acid esters can be very easily incorporated into formulations, especially cosmetic formulations.

[0017] Therefore, the subject of the present invention is xylitol carboxylic acid esters, which include carboxylic acid esters of xylitol, carboxylic acid esters of 1,4-anhydroxylitol, carboxylic acid esters of 1,4-anhydroarabinitol, and carboxylic acid esters of 1,4-anhydroribitol, wherein the xylitol residues contained in the xylitol carboxylic acid esters are the same as the 1,4-anhydroxylitol residues, 1,4-anhydroarabinitol residues, and 1,4-anhydroribitol residues contained in the xylitol carboxylic acid esters. The xylitol carboxylic acid ester has a total weight ratio of 96:4 or more, preferably greater than 97:3, particularly preferably greater than 98:2, and most preferably greater than 99:1, characterized in that the molar ratio of esterified primary hydroxyl groups to esterified secondary hydroxyl groups in the carboxylic acid ester of xylitol is 80:20 to 20:80, preferably 75:25 to 25:75, even more preferably 70:30 to 30:70, and even more preferably 65:35 to 40:60.

[0018] The term "xylitol carboxylic acid ester" as used herein encompasses compositions containing at least 30% by weight, preferably at least 40% by weight, more preferably at least 50% by weight, and particularly preferably at least 70% by weight of a xylitol carboxylic acid ester relative to the total weight of the composition. Furthermore, by-products from the respective production processes, such as 1,4-anhydroxylitol carboxylic acid esters, 1,4-anhydroarabinitol carboxylic acid esters, and 1,4-anhydroribitol carboxylic acid esters, as well as unreacted reactants, may also be present.

[0019] The term "carboxylic acid ester of xylitol" in the present invention refers to the pure xylitol compound.

[0020] The term "carboxylic acid ester of 1,4-anhydroxylitol" in the present invention refers to the pure 1,4-anhydroxylitol compound.

[0021] The term "carboxylic acid ester of 1,4-anhydroarabinitol" in the present invention means a pure 1,4-anhydroarabinitol compound.

[0022] The term "carboxylic acid ester of 1,4-anhydroribitol" in the present invention refers to a pure 1,4-anhydroribitol compound.

[0023] The use of this term is based on the conventional nomenclature of polyol esters. Polyol esters are known to be prone to dehydration during their synthesis, and therefore the resulting products are mixed compositions. For example, those skilled in the art will understand the term "sorbitan esters" to mean a mixture containing not only esters of 1,4-sorbitan (1,4-anhydrosorbitol) and esters of 1,5-sorbitan (1,5-anhydrosorbitol), but also esters of isosorbide and esters of sorbitol, as well as free sorbitol; see Food emulsifiers and their applications, 1997, p. 26.

[0024] The phrase "xylitol carboxylic acid esters comprising a carboxylic acid ester of xylitol, a carboxylic acid ester of 1,4-anhydroxylitol, a carboxylic acid ester of 1,4-anhydroarabinitol, and a carboxylic acid ester of 1,4-anhydroribitol, wherein the weight ratio of xylitol residues contained in the carboxylic acid ester to the total of all 1,4-anhydroxylitol residues, 1,4-anhydroarabinitol residues, and 1,4-anhydroribitol residues contained in the carboxylic acid ester is 96:4 or more" clearly and unambiguously indicates that in the xylitol carboxylic acid esters according to the present invention, the content of at least one selected from the carboxylic acid ester of 1,4-anhydroxylitol, the carboxylic acid ester of 1,4-anhydroarabinitol, and the carboxylic acid ester of 1,4-anhydroribitol must not be 0 (zero), because division by 0 is not defined.

[0025] Unless otherwise specified, all percentages (%) listed are by weight.

[0026] The weight ratio of xylitol residues contained in a xylitol carboxylic acid ester according to the present invention to the sum of all 1,4-anhydroxylitol residues, 1,4-anhydroarabinitol residues, and 1,4-anhydroribitol residues contained in the xylitol carboxylic acid ester according to the present invention can be determined by high-performance liquid chromatography (HPLC). This method involves alkaline hydrolysis of the xylitol carboxylic acid ester to be analyzed, removing the carboxylic acid, and analyzing xylitol and its degradation products, 1,4-anhydroxylitol, 1,4-anhydroarabinitol, and 1,4-anhydroribitol.

[0027] To this end, 150 mg of the xylitol carboxylic acid ester to be analyzed is placed in 2.00 mL of 1 M aqueous KOH solution and hydrolyzed at 95 °C for 30 minutes with stirring. The reaction mixture is then cooled to room temperature and adjusted to pH 2-3 with 2 M aqueous hydrochloric acid. The resulting carboxylic acid is then extracted with diethyl ether (3 × 3.00 mL), and the organic supernatant is removed with a pipette after each extraction. After extraction, the remaining ether is removed by heating the aqueous solution to 50 °C over 20 minutes with stirring (boiling point of diethyl ether: 34.6 °C). The resulting solution is filled to 10.0 mL with distilled H2O and then diluted 1:10. An aliquot of the solution is analyzed by HPLC. The analysis is performed under the following conditions: Column: Aminex HPX-87C column 300 x 7.8 mm Eluent: H2O Injection volume: 10.0μL Flow rate: 0.60mL / min Column temperature: 50℃ Detector: G1362A / 1260 RID (Agilent), 35°C Measurement time: 30.0 minutes

[0028] An ion exchange process separates xylitol and its degradation products.

[0029] For evaluation, the ratio of the xylitol peak area to the sum of the peak areas of 1,4-anhydroxylitol, 1,4-anhydroarabinitol, and 1,4-anhydroribitol is calculated. Reference substances for xylitol degradation products are commercially available, but alternatively can be obtained by heating neat xylitol in the presence of an acidic (>140°C) or basic (>180°C) catalyst.

[0030] The molar ratio of esterified primary hydroxyl groups to esterified secondary hydroxyl groups in the carboxylic acid esters of xylitol can be determined by: 13 This is performed by C-NMR spectroscopy. For sample preparation, 50-70 mg of material is dissolved in 1 mL of a deuterated solvent with the addition of a relaxation promoter (chromium(III) acetylacetonate, 1%). Depending on the product characteristics, DMSO-d6, CDCl3, and methanol-d4 have been found to be suitable solvents. If the sample does not dissolve completely in one of the solvents, a solvent mixture must be found. The prepared sample solution is transferred to a 5 mm NMR tube and introduced into the NMR spectrometer. NMR spectroscopy can, in principle, be performed using commercially available NMR instruments. For this NMR spectroscopy, a Bruker Avance 400 instrument was used. The spectra were recorded with the following parameters: Temperature: T = 295 K, delay time: D1 = 2 s, number of scans: NS = 2048, transmitter frequency offset: O1P = 110 ppm, sweep width: SW = 300 ppm, sample head: PA BBI 400 S1 H-BB-D-05-Z. Resonance signals are recorded relative to the chemical shifts of tetramethylsilane (TMS = 0 ppm) as an internal standard. Equivalent results can be obtained with other commercially available NMR instruments using the same operating parameters. Quantification is performed by determining the area under each resonance signal, i.e., the area enclosed by the signal from the baseline. For this NMR spectroscopy measurement, integration was performed using TOPSPIN (version 3.0) software. For accurate identification of esterified primary and secondary hydroxyl groups, DEPT spectra were primarily recorded. The molar ratio of esterified primary to secondary hydroxyl groups was determined by subtracting the integral P (signals of esterified primary hydroxyl groups) from the integral C (signals of ester carbonyl groups). This yields the integral S of the signals of esterified secondary hydroxyl groups, which cannot be determined directly due to overlap with other signals.

[0031] P = esterified primary hydroxyl group [R- C Integral value of H2-OC(O)R group C = integral value of ester carbonyl group S = CP = esterified secondary hydroxyl group [R2- C Integral value of H-OC(O)R group The calculated P to S ratio corresponds to the molar ratio of esterified primary hydroxyl groups to esterified secondary hydroxyl groups in the carboxylic acid ester of xylitol.

[0032] According to the invention, preference is given to xylitol carboxylic acid esters, characterized in that the carboxylic acid component is derived from a carboxylic acid containing 2 to 34, preferably 4 to 24, particularly preferably 6 to 22 carbon atoms.

[0033] The carboxylic acid component is preferably derived from a natural fatty acid or a mixture thereof, and mixtures of natural fatty acids are preferred according to the invention, in particular mixtures in which no carboxylic acid chain length has a proportion of more than 95% by weight, in particular more than 99% by weight, in the overall chain length distribution.

[0034] Natural fatty acids can be prepared from naturally occurring vegetable or animal oils and preferably contain 6 to 30 carbon atoms, especially 8 to 22 carbon atoms. Natural fatty acids are generally unbranched and usually contain an even number of carbon atoms. Any double bonds have a cis configuration. Examples include caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, pelargonic acid (obtained, for example, by ozonolysis or oxidative cleavage of oleic acid), isostearic acid, stearic acid, 12-hydroxystearic acid, dihydroxystearic acid, undecylenic acid (obtained by thermal decomposition of ricinoleic acid), oleic acid, linoleic acid, linolenic acid, petroselinic acid, elaidic acid, arachidic acid, behenic acid, erucic acid, gadoleic acid, linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid. According to the present invention, particular preference is given to xylitol carboxylic acid esters, characterized in that the carboxylic acid component is derived from a mixture of fatty acids selected from at least two selected from the group consisting of caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, pelargonic acid (obtained, for example, by ozonolysis or oxidative cleavage of oleic acid), isostearic acid, stearic acid, 12-hydroxystearic acid, dihydroxystearic acid, undecylenic acid (obtained, for example, by thermal decomposition of ricinoleic acid), oleic acid, linoleic acid, linolenic acid, petroselinic acid, elaidic acid, arachidic acid, behenic acid, erucic acid, gadoleic acid, linolenic acid, eicosapentaenoic acid, docosahexaenoic acid and arachidonic acid.

[0035] According to the present invention, preferred is a xylitol carboxylic acid ester characterized in that the average degree of esterification of the carboxylic acid ester of xylitol contained therein is 1.0 to 4.0, preferably 1.0 to 3.0, particularly preferably 1.1 to 2.7, and particularly preferably 1.3 to 2.6. Alternatively, according to the present invention, preferred is a xylitol carboxylic acid ester characterized in that the average degree of esterification of the carboxylic acid ester of xylitol contained therein is 2.7 to 4.0.

[0036] The average degree of esterification of the xylitol carboxylic acid esters contained in the xylitol carboxylic acid esters according to the present invention can be determined, for example, by first determining the content of free xylitol and its degradation products, 1,4-anhydroxylitol, 1,4-anhydroarabinitol, and 1,4-anhydroribitol, in a sample of the xylitol carboxylic acid ester by GC or HPLC. Furthermore, the saponification value, acid value, and content of free fatty acids and neutralized fatty acids (e.g., by GC as described in the "Determination of the Free Carboxylic Acid Content" section below) must be determined. The determination of the carboxylic acid composition after alkaline saponification provides the average molar mass of the carboxylic acid residues contained in the xylitol carboxylic acid esters. This can be used to calculate the average degree of esterification.

[0037] According to the present invention, the xylitol carboxylic acid esters contained preferably include xylitol monoesters, xylitol diesters, and xylitol triesters, and the xylitol triesters are preferably contained in an amount of 10 to 50% by weight, preferably 15 to 45% by weight, and particularly preferably 20 to 40% by weight, based on the total amount of xylitol carboxylic acid esters contained. In this regard, further according to the present invention, the xylitol carboxylic acid esters contained preferably include xylitol monoesters, xylitol diesters, xylitol triesters, and xylitol tetraesters.

[0038] According to the invention, preference is given to xylitol carboxylic acid esters characterized by containing 0.05% to 40% by weight, preferably 0.2% to 25% by weight, particularly preferably 0.5% to 10% by weight of free xylitol, where the weight percentages are based on the total xylitol carboxylic acid ester.

[0039] To quantify the xylitol content of the xylitol carboxylic acid esters according to the present invention by GC, a portion of the sample is dissolved in pyridine:chloroform (4:1). 0.25 mL of this solution is mixed with 0.5 mL of MSTFA [N-methyl-N-(trimethylsilyl)trifluoroacetamide] and 0.5 mL of a mixture of N-trimethylsilylimidazole and pyridine (11:39). The alcohol is quantitatively converted to its trimethylsilyl ether by reaction at 80°C (30 min) and then analyzed by GC / FID. This is carried out using a gas chromatograph equipped with a split / splitless injector, a capillary column, and a flame ionization detector under the following conditions:

[0040] Injector: 290℃, split 30mL Injection volume: 1μL Column: 50m x 0.32mm HP5 1.05μm Carrier gas: Hydrogen, constant flow, 2 mL / min Temperature program: 100°C to 140°C at 10°C / min, then 140°C to 300°C at 5°C / min, then conditioning at 300°C for 5 minutes Detector: FID, at 310°C Hydrogen 30mL / min Air 400mL / min Make-up gas 12mL / min

[0041] Xylitol is separated and its weight percentage is determined by the internal standard method, for which the GC system is calibrated by analyzing a mixture of xylitol and an internal standard of known composition.

[0042] According to the invention, xylitol carboxylic acids are preferred which are characterized by comprising less than 25% by weight, preferably 0.01% to 20% by weight, particularly preferably 0.05% to 10% by weight, of at least one free carboxylic acid, the percentages being based on the total xylitol carboxylic acid esters, whereby the at least one free carboxylic acid can be present in protonated or neutralized form.

[0043] To determine the content of free carboxylic acids in the xylitol carboxylic acid ester of the present invention, the acid value is first determined. The weight percentage can be determined from the acid value and the molecular weight of the fatty acid. Suitable methods for determining the acid value are, in particular, those according to DGF CV 2, DIN EN ISO 2114, Ph.Eur.2.5.1, ISO 3682, and ASTM D 974. Those skilled in the art will recognize that, in the case of a mixture of carboxylic acids, GC analysis can be additionally performed after saponification of the xylitol carboxylic acid ester to determine the average molecular weight of the carboxylic acid mixture present. For this purpose, 0.6 g of the xylitol carboxylic acid ester of the present invention is boiled under reflux for 4 hours in 25 mL of a 0.5 M KOH solution in ethanol. The pH is then adjusted to 2-3 with sulfuric acid, and the free carboxylic acids are separated by extraction three times with 1 volume each of petroleum ether. The combined extracts are concentrated to approximately 10 mL by evaporation. Suitable methods for determining the fatty acid distribution are those according to DGF C VI 11a, DGF C-VI 10a, and GAT Ring Test 7 / 99. A 0.5 mL aliquot of the petroleum ether extract obtained above is mixed with 0.5 mL of MTBE and 1 mL of trimethylanilinium hydroxide (0.2 M in methanol) in an autosampler vial and analyzed by GC. This is performed using a gas chromatograph equipped with a split / splitless injector, a capillary column, and a flame ionization detector under the following conditions: Injector: 290℃, split 30mL Injection volume: 1μL Column: 30m x 0.32mm HP1 0.25μm Carrier gas: Helium, head pressure 70kPa Temperature program: 80°C to 300°C at 8°C / min, followed by conditioning at 300°C for 20 min Detector: FID, at 320°C Hydrogen 35mL / min Air 240mL / min Make-up gas 12mL / min

[0044] The carboxylic acids are separated into their methyl esters according to their carbon chain length. By evaluating the peak areas, the weight ratios of these carboxylic acid methyl esters to each other can be determined, from which the ratios of the amounts of substance of the related carboxylic acids can be determined using their respective molecular weights. Furthermore, the average molecular weight of this fatty acid mixture can be determined: [Table 1]

[0045] According to the present invention, preferred xylitol carboxylic acid esters are characterized in that the secondary ester positional isomer is contained in an amount of 5% by weight to 25% by weight, preferably 7% by weight to 15% by weight, and particularly preferably 9% by weight to 13% by weight of the total monoester components of the carboxylic acid ester of xylitol.

[0046] According to the present invention, preferred xylitol carboxylic acid esters are characterized in that all monoester components of the carboxylic acid esters of xylitol and all diester components of the carboxylic acid esters of xylitol each contain at least two positional isomers.

[0047] According to the present invention, a preferred xylitol carboxylic acid ester is characterized in that, in the total diester components of the xylitol carboxylic acid ester, a positional isomer in which at least one secondary hydroxyl group is esterified is contained in an amount of 25% by weight to 45% by weight, preferably 28% by weight to 39% by weight, and particularly preferably 30% by weight to 37% by weight.

[0048] The determination of the content of secondary ester positional isomers in the total monoester components of xylitol carboxylic acid esters according to the present invention, the content of triester species relative to the sum of all xylitol carboxylic acid esters contained, and the content of positional isomers in which at least one secondary hydroxyl group is esterified in the total diester components can be carried out by gas chromatography, optionally combined with mass spectrometry (GC-FID and GC-MS): First, 10 mg of a sample of the corresponding xylitol carboxylic acid ester is dissolved in 1.5 mL of trichloromethane, and then 0.15 mL of N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) is added. Derivatization is carried out at 80 °C for 30 minutes. A sample of the resulting clear solution is analyzed by GC-FID and GC-MS. The measurement parameters are as follows: Gas chromatograph: Agilent 7890 Column: Agilent HP-5 (50 m, 0.32 mm, 0.5 μm) Flow rate: Hydrogen constant at 2 mL / min (GC-MS: Helium) Temperature control: 80°C, 8°C / min; 300°C, 30 min, injector 1 μL, split 1:20, detector 310°C Detector: FID, 310℃ / GC-MS Scan 35-650 d

[0049] In GC-FID analysis, the esters in a sample are separated according to their total chain length. The proportion of each ester species relative to one another is determined by the area ratio of the GC-FID peaks. Peaks are identified / assigned to individual ester species by GC-MS and, if necessary, by comparison with the retention times of separately prepared and separated standards, e.g., mono- and diesters in which only the primary hydroxyl groups are esterified. This method also allows the content of free protonated carboxylic acids and, in addition, free neutralized carboxylic acids, to be determined, since these are also derivatized.

[0050] A further subject of the present invention is an enzymatic process for the production of xylitol carboxylic acid esters, preferably xylitol carboxylic acid esters according to the invention, comprising the steps of: A) providing xylitol and at least one acyl donor, preferably a fatty acid acyl donor, in particular a fatty acid acyl donor selected from fatty acid esters and fatty acids, particularly preferably a fatty acid, B) reacting xylitol with at least one acyl donor in the presence of a lipase at a temperature between 75°C and 110°C, preferably between 77°C and 100°C, even more preferably between 80°C and 95°C, to obtain xylitol carboxylic acid esters; and optionally C) a process step for purifying xylitol carboxylic acid esters; The method includes:

[0051] According to the present invention, any acyl group donor can be used. These include, for example, carboxylic acid esters or carboxylic acids themselves, and mixtures thereof. Preferably, according to the present invention, the carboxylic acid esters used as acyl group donors are selected from esters based on alkanols and polyols having up to 6 carbon atoms, particularly preferably esters based on alkanols and polyols having up to 3 carbon atoms, and very particularly preferably glycerol esters. Particularly preferably, according to the present invention, the carboxylic acid esters used as acyl group donors are selected from triglycerides, especially natural fats and oils, particularly preferably from the group including coconut oil, palm kernel oil, olive oil, palm oil, argan oil, castor oil, linseed oil, babassu oil, rapeseed oil, algae oil, sesame oil, soybean oil, avocado oil, jojoba oil, safflower oil, almond oil, cottonseed oil, shea butter, sunflower oil, cupuaçu butter, and oils with a high proportion of polyunsaturated fatty acids (PUFAS), and particularly preferably from the group consisting of these. In particular, sorbitan esters, monoglycerides and diglycerides containing acyl groups, which will be described later, can also be preferably used.

[0052] Particularly preferably, according to the invention, the acyl donor is selected from fatty acid acyl donors which provide an acyl group selected in particular from the group of acyl groups of natural fatty acids. Preferred fatty acids in this context are those mentioned above in connection with the xylitol carboxylic acid esters according to the invention, preferably with the same preference for the fatty acids forming the carboxylic acid component.

[0053] Preferably, according to the invention, carboxylic acids, in particular fatty acids, are used as acyl group donors, whereby the fatty acids specifically mentioned above in connection with the xylitol carboxylic acid esters according to the invention are preferably used with the same priority.

[0054] Alternatively and preferably according to the invention, a mixture of fatty acids and glycerol fatty acid esters is used as acyl group donors, wherein the fatty acids specifically mentioned above in connection with the xylitol carboxylic acid esters according to the invention are preferably used with equal priority in both the fatty acid and glycerol fatty acid components.

[0055] The mixture of fatty acid and glycerin fatty acid ester used preferably has a weight ratio of fatty acid to glycerin fatty acid ester of 80:20 to 99:1, preferably 90:10 to 99:1, particularly preferably 95:5 to 99:1.

[0056] A preferred process according to the invention is characterized in that xylitol and at least one acyl donor make up at least 80% by weight, preferably at least 90% by weight, particularly preferably at least 95% by weight, of the total reaction batch at the start of process step B).

[0057] In this context, the entire reaction batch may contain very little, if any, solvent, since it consists largely of the reactants, i.e., xylitol and acyl donor. Based on the above, it is clear that the acyl donor is not encompassed by the term "solvent" in the process according to the invention.

[0058] Possible solvents include, for example, ketones such as methyl isobutyl ketone or cyclohexanone, sterically hindered secondary alcohols such as 2-butyl-1-octanol, methylcyclohexanol, 1-methoxy-2-propanol, 2,3-butanediol, 2-octanol, diacetone alcohol, 2-methyl-2-butanol, and ethers such as 1,4-dioxane, tetrahydrofuran, and Varonic APM. The solvent is contained in a total amount of less than 20% by weight, preferably less than 10% by weight, and particularly less than 5% by weight, based on the total reaction batch. The expression "contains less than X% by weight at most" can be considered as "having a content of less than X% by weight."

[0059] Particularly preferably, the process according to the invention is carried out solvent-free.

[0060] A preferred method according to the present invention is characterized in that the molar ratio of the provided xylitol to the acyl groups contained in all the provided acyl group donors is in the range of 1.00:0.30 to 1.00:5.00, preferably 1.00:0.70 to 1.00:3.00, particularly preferably 1.00:1.00 to 1.00:2.25, or particularly preferably 1.00:2.3 to 1.00:4.50.

[0061] A preferred method according to the present invention is characterized in that process step A) comprises blending xylitol with at least one acyl donor for at least 10 minutes, preferably 30 minutes, even more preferably 60 minutes, wherein blending is preferably carried out within a temperature range of 80°C to 120°C, preferably 90°C to 120°C, even more preferably 95°C to 120°C, even more preferably 100°C to 120°C.

[0062] According to the invention, the lipase preferably used in process step B) is immobilized on a solid support.

[0063] Lipases preferably used according to the invention in process step B) are lipase from Thermomyces lanuginosus (accession number O59952), lipases A and B from Candida antarctica (accession number P41365), lipase from Mucor miehei (accession number P19515), lipase from Humicola sp. (accession number O59952), lipase from Rhizomucor javanicus (accession number S32492), lipase from Rhizopus oryzae (accession number P61872), lipase from Candida rugosa ... Lipases from Rhizopus niveus (accession number P61871), Penicillium camemberti (accession number P25234), Aspergillus niger (ABG73613, ABG73614, and ABG37906), and Penicillium cyclopium (accession number P32949, P20261, P32946, P32947, P3294, and P32949). and lipases having at least 60%, preferably at least 80%, preferably at least 90%, particularly preferably at least 95%, 98% or 99% homology thereto at the amino acid level, respectively, wherein lipases A and B from Candida antarctica (accession number P41365) are particularly preferred.

[0064] The accession numbers cited in this invention correspond to entries in the NCBI ProteinBank database as of January 1, 2017, and as a general rule, the version number of an entry is displayed as a ".number" such as ".1".

[0065] Enzymes that are homologous at the amino acid level preferably have at least 50%, in particular at least 90%, enzymatic activity at the propyl laurate unit as defined in the present invention compared to the reference sequence.

[0066] To measure enzyme activity in PLU (propyl laurate units), 1-propanol and lauric acid are mixed uniformly at an equimolar ratio at 60°C. The enzyme is added to initiate the reaction, which is then timed. Samples are taken from the reaction mixture at regular intervals, and the content of reacted lauric acid is measured by titration with potassium hydroxide solution. The enzyme activity in PLU is determined by the rate at which 1 g of the enzyme synthesizes 1 micromole of propyl laurate per minute at 60°C. See U.S. Patent Application Publication No. 20070087418, especially paragraph

[0185] .

[0067] Examples of commercially available lipases, which are also preferably used in the method according to the invention, are the commercially available products Lipozyme TL IM, Novozym 435, Lipozyme IM 20, Lipase SP382, Lipase SP525, Lipase SP523 (all commercially available from Novozymes A / S, Bagsvaer, Denmark), Chirazyme L2, Chirazyme L5, Chirazyme L8, Chirazyme L9 (all commercially available from Roche Molecular Biochemicals, Mannheim, Germany), CALB Immo Plus™ from Purolite, and Lipase M "Amano", Lipase F-AP. 15 “Amano”, Lipase AY “Amano”, Lipase N “Amano”, Lipase R “Amano”, Lipase A “Amano”, Lipase D “Amano”, and Lipase G “Amano” (all commercially available products from Amano Co., Ltd., Japan).

[0068] "Homology at the amino acid level" in the present invention is understood to mean "amino acid identity", which can be determined by known methods. Generally, specific computer programs with algorithms that take into account specific requirements are used. A preferred method for determining identity first generates a maximum alignment between the sequences to be compared. Computer programs for determining identity include, but are not limited to, the GCG program package, including: - GAP(Deveroy, J. et al., Nucleic Acid Research 12 (1984), p.387, Genetics Computer Group University of Wisconsin, Medicine (WI), and - BLASTP, BLASTN and FASTA (Altschul, S. et al., Journal of Molecular Biology 215 (1990), p. 403-410. BLAST programs are available from the National Center for Biotechnology Information (NCBI) and other sources (BLAST Handbook, Altschul S. et al., NCBI NLM NIH Bethesda ND 22894; Altschul S. et al., supra).

[0069] Those skilled in the art will recognize that various computer programs are available for calculating the similarity or identity between two nucleotide sequences or amino acid sequences.For example, the identity percentage between two amino acid sequences can be determined by, for example, the algorithm by Needleman and Wunsch (J. Mol. Biol. (48): 444-453 (1970)), which is integrated into the GAP program of GCG software package (available at http: / / www.gcg.com), and uses Blossom 62 matrix or PAM250 matrix, gap weight of 16, 14, 12, 10, 8, 6 or 4, and length weight of 1, 2, 3, 4, 5 or 6.Those skilled in the art will recognize that although the use of different parameters will produce slightly different results, the overall identity percentage between two amino acid sequences will not be significantly different.The Blossom 62 matrix is ​​usually used with default settings (gap weight: 12, length weight: 1).

[0070] In the present invention, 60% identity according to the above algorithm means 60% homology, and the same applies to higher identities.

[0071] Preferably, according to the invention, in process step B) 500 PLU to 2000 PLU, preferably 200 PLU to 1500 PLU, particularly preferably 25 PLU to 1250 PLU of lipase are used per g of xylitol to be converted.

[0072] Preferably, according to the invention, process step B) is carried out at a pressure of less than 1 bar, preferably less than 0.5 bar, particularly preferably less than 0.1 bar.

[0073] Alternatively and preferably according to the invention, process step B) is carried out in a bubble column reactor in which the reaction batch is passed through with at least one inert gas, this gas being preferably selected from the group comprising nitrogen and argon, preferably selected from the group consisting of nitrogen and argon. In this context, it is preferred according to the invention that the gas flow is between 1 and 60 kg / h, preferably between 5 and 25 kg / h, even more preferably between 10 and 14 kg / h.

[0074] Preferably, according to the invention, process step B) is characterized in that process step B) is terminated at the latest 180 hours, preferably 120 hours, particularly preferably 100 hours after addition of the lipase.

[0075] A preferred process according to the invention is characterized in that the by-products formed in process step B), such as water if the acyl donor used is an acid or the corresponding alcohol if the acyl donor used is an ester, are removed, for example by distillation.

[0076] Process step C) of the method according to the invention involves the purification of the xylitol carboxylic acid esters. For this purpose, all methodologies can be employed which allow obtaining xylitol carboxylic acid esters in higher concentrations.

[0077] Preferably, according to the invention, the process according to the invention comprises, in process step C), the removal of the lipase used in the process according to the invention.

[0078] When the lipase is immobilized on a carrier, according to the present invention, it is preferable to remove the lipase by filtration using a filter having a mesh size of 0.1 μm to 1250 μm, preferably 0.5 μm to 100 μm, particularly a bag filter.

[0079] Preferably, according to the invention, the process of the invention is characterized in that no molecular sieves are used in the process.

[0080] Preferably, according to the invention, the method of the invention is characterized in that the substrate is used in a state where it is not immobilized on a solid support, such as for example silica.

[0081] A further subject of the present invention are xylitol carboxylic acid esters obtainable by the process according to the invention.

[0082] A further subject of the present invention is the use of the xylitol carboxylic acid esters according to the invention and / or obtainable by the process according to the invention as viscosity modifiers, care active ingredients, foam boosters or solubilizers, antibacterial agents, antistatic agents, binders, corrosion inhibitors, dispersants, emulsifiers, film-forming agents, humectants, opacifiers, oral care agents, preservatives, skin care agents, hydrophilic emollients, foam stabilizers and non-ionic surfactants, preferably as viscosity modifiers, emulsifiers, antibacterial agents and hydrophilic emollients, particularly preferably as viscosity modifiers, in particular as thickeners, in particular in cleaning or care formulations.

[0083] The following examples are provided to illustrate the present invention, and are not intended to limit the scope of the present invention, the scope of which is clear from the entire specification and claims, to the embodiments given in the examples.

[0084] Working Example: Various xylitol carboxylic acid esters were prepared as follows.

[0085] How to determine the number of colors Aliquots (approximately 10 g; enough to fill the cuvette) were measured in a Lico 690 spectrophotometer in an 11 mm round cuvette at room temperature or 90° C., and the resulting color numbers were recorded.

[0086] Example 1: Enzymatic esterification of xylitol with 2.00 eq. caprylic acid (according to the invention) A mixture of xylitol (60.0 g, 0.394 mol, 1.00 eq.) and caprylic acid (acid value 389 mg KOH / g, >98%, 113.70 g, 0.788 mol, 2.00 eq.) was heated to 80 °C with stirring and N2 flow. After 1 h, immobilized enzyme Candida antarctica lipase B (5.21 g; Purolite D5619, equivalent to 45110 PLU) was added. The mixture was stirred at 80 °C and 15 mbar for 24 h, during which time the water produced was continuously distilled off. The mixture was then filtered at 80 °C through a Büchner funnel with a black ribbon filter to remove the enzyme. The resulting product was homogeneous in the melt, colorless, and had an acid value of 1.2 mg KOH / g. The content of triesters, which corresponds to the total of all xylitol carboxylic acid esters contained, was 27% by weight, as determined by the area percentage of the GC-FID peak.

[0087] Example 2: Enzymatic esterification of xylitol with 2.00 eq. of caprylic / capric acid (according to the invention) A mixture of xylitol (70.8 g, 0.465 mol, 1.00 eq.) and a mixture of caprylic and capric acids (acid value 362 mg KOH / g, caprylic / capric ratio 60:40, 146.0 g, 0.930 mol, 2.00 eq.) was heated to 90 °C over 1 h with stirring and N2 sparging. After cooling to 85 °C, immobilized enzyme Candida antarctica lipase B (6.50 g; Purolite D5619, equivalent to 56280 PLU) was added. The mixture was stirred at 85 °C and 50 mbar for 24 h, during which the water produced was continuously distilled off. The mixture was then filtered at 80 °C using a Büchner funnel equipped with a black ribbon filter to remove the enzyme. The resulting product was homogeneous and colorless in the melt and had an acid value of 2.7 mg KOH / g. The triester content, calculated by the GC-FID peak area percentage, was 26 wt. %, corresponding to the total of all xylitol carboxylic acid esters present.

[0088] Example 3: Enzymatic esterification of xylitol with 1.80 eq. of caprylic / capric acid (according to the invention) A mixture of xylitol (75.7 g, 0.497 mol, 1.00 eq.) and a mixture of caprylic and capric acids (acid value 362 mg KOH / g, caprylic / capric ratio 60:40, 140.5 g, 0.895 mol, 1.80 eq.) was heated to 90 °C over 1 h with stirring and N2 sparging. After cooling to 85 °C, immobilized enzyme Candida antarctica lipase B (6.48 g; equivalent to Purolite D5619, 56106 PLU) was added. The mixture was stirred at 85 °C and 50 mbar for 24 h, during which time the water produced was continuously distilled off. The mixture was then filtered at 80 °C using a Büchner funnel equipped with a black ribbon filter to remove the enzyme. The resulting product was homogeneous and colorless in the melt and had an acid value of 1.5 mg KOH / g. The triester content, calculated by the GC-FID peak area percentage, corresponding to the total of all xylitol carboxylic acid esters contained, was 25 wt.%.

[0089] Example 4: Enzymatic esterification of xylitol with 2.00 eq. of stearic acid (according to the invention) A mixture of xylitol (40.00 g, 0.263 mol, 1.00 eq.) and stearic acid (acid value 198 mg KOH / g, >92%, 148.18 g, 0.526 mol, 2.00 eq.) was heated to 90 °C with stirring and N2 sparging. After 1 h, immobilized enzyme Candida antarctica lipase B (5.65 g; Purolite D5619, equivalent to 48919 PLU) was added. The mixture was stirred at 90 °C and 15 mbar for 24 h, during which time the water produced was continuously distilled off. The mixture was then filtered at 80 °C through a Büchner funnel with a black ribbon filter to remove the enzyme. The resulting product was homogeneous and clear in the melt, pale yellow in color, and had an acid value of 1.3 mg KOH / g. The content of triesters, which corresponds to the total of all xylitol carboxylic acid esters contained, was 35% by weight, as determined by the area percentage of the GC-FID peak.

[0090] Example 5: Enzymatic esterification of xylitol with 2.00 eq. of oleic acid (according to the invention) A mixture of xylitol (40.00 g, 0.263 mol, 1.00 eq.) and oleic acid (acid value 200 mg KOH / g, iodine value 92.3 g I2 / 100 g, 147.5 g, 0.526 mol, 2.00 eq.) was heated to 90 °C with stirring and N2 flow. After 1 h, immobilized enzyme Candida antarctica lipase B (5.65 g; Purolite D5619, equivalent to 48919 PLU) was added. The mixture was stirred at 80 °C and 15 mbar for 24 h, during which time the water produced was continuously distilled off. The mixture was then filtered at 80 °C through a Büchner funnel with a black ribbon filter to remove the enzyme. The resulting product was homogeneous and clear in the melt, yellowish in color, and had an acid value of 1.1 mg KOH / g. The content of triesters, which corresponds to the total of all xylitol carboxylic acid esters contained, was 34% by weight, as determined by the area percentage of the GC-FID peak.

[0091] Example 6: Xylyl Caprate / Caprylate (not according to the invention) Here, GiO (registered trademark)-103, a commercially available product manufactured by GiOrbis Laboratories, was used as the sample.

[0092] Example 7: Esterification of xylitol with 2.00 eq. of caprylic acid (not according to the present invention) as described in Korean Patent No. 101939851 Esterification of xylitol with fatty acids at elevated temperatures in the presence of an acid catalyst is described, for example, in Korean Patent No. 101939851 or European Patent Application Publication No. 2902009. A mixture of xylitol (76.1 g, 0.500 mol, 1.00 eq.) and caprylic acid (acid value 389 mg KOH / g, >98%, 144.2 g, 1.00 mol, 2.00 eq.) was heated to 200°C with stirring and N2 flow after the addition of p-toluenesulfonic acid (0.29 g, 0.2% relative to caprylic acid). The mixture was then stirred at this temperature for 8 hours, during which the water produced was continuously distilled off until an acid value of 0.7 mg KOH / g was reached. The resulting product was yellow to brown in color and had a Gardner color of 6.4.

[0093] Example 8: Enzymatic esterification of xylitol with 2.00 eq. caprylic acid at low temperature (not according to the invention) A mixture of xylitol (75.2 g, 0.494 mol, 1.00 eq.) and caprylic acid (acid value 389 mg KOH / g, >98%, 142.6 g, 0.989 mol, 2.00 eq.) was enzymatically reacted for 29 hours at 60 °C with stirring and N2 sparging as described by Basri et al. (Carbohydr. Res. 2011, 346, 472-479). The resulting product was heterogeneous in the melt (i.e., it formed two phases) and had an acid value of approximately 360 mg KOH / g.

[0094] Table 1 compares the parameters determined for examples according to the invention and examples not according to the invention.

[0095] [Table 2]

[0096] Example 9: Thickening performance in cosmetic formulations The thickening effect of Examples 1, 2, and 3 according to the present invention was evaluated in comparison with a thickener not according to the present invention. To this end, a cosmetic formulation consisting of 9% SLES, 3% cocamidopropyl betaine, and 0.7% NaCl in water was prepared. The pH of the formulation was adjusted to 5.2 with citric acid. 1.1% of each of the above-mentioned examples was blended into the formulation over 30 minutes with stirring at 60°C, and the viscosity was measured at 22°C using a Brookfield viscometer (spindle 62, 30 rpm). The viscosity measurement results are shown in Table 2.

[0097] [Table 3]

[0098] The results shown in Table 2 show that the formulations obtained using Examples 1, 2 and 3 according to the invention have higher viscosities than the formulations obtained using the examples not according to the invention.

[0099] Example formulation [Table 4-1]

[0100] [Table 4-2]

[0101] [Table 4-3]

[0102] [Table 4-4]

[0103]

Table 4-5

[0104]

Table 4-6

[0105]

Table 4-7

[0106]

Table 4-8

[0107]

Table 4-9

[0108]

Table 4-10

[0109]

Table 4-11

[0110]

Table 4-12

[0111]

Table 4-13

[0112]

Table 4-14

[0113]

Table 4-15

[0114]

Table 4-16

[0115]

Table 4-17

[0116]

Table 4-18

[0117]

Table 4-19

[0118]

Table 4-20

[0119]

Table 4-21

[0120]

Table 4-22

[0121]

Table 4-23

[0122]

Table 4-24

[0123]

Table 4-25

[0124]

Table 4-26

[0125]

Table 4-27

[0126]

Table 4-28

[0127]

Table 4-29

[0128]

Table 4-30

[0129]

Table 4-31

[0130]

Table 4-32

[0131]

Table 4-33

[0132]

Table 4-34

[0133]

Table 4-35

[0134]

Table 4-36

[0135]

Table 4-37

Claims

1. 1. A xylitol carboxylic acid ester composition comprising a carboxylic acid ester of xylitol, a carboxylic acid ester of 1,4-anhydroxylitol, a carboxylic acid ester of 1,4-anhydroarabinitol, and a carboxylic acid ester of 1,4-anhydroribitol, wherein the weight ratio of xylitol residues to the total of all 1,4-anhydroxylitol residues, 1,4-anhydroarabinitol residues, and 1,4-anhydroribitol residues contained in the xylitol carboxylic acid ester composition is greater than 99:1 based on the xylitol residues contained in the xylitol carboxylic acid ester composition, and the molar ratio of esterified primary hydroxyl groups to esterified secondary hydroxyl groups in the carboxylic acid ester of xylitol is 80:20 to 20:

80.

2. 2. The xylitol carboxylic acid ester composition of claim 1, wherein the carboxylic acid component is derived from a carboxylic acid containing 2 to 34 carbon atoms.

3. The xylitol carboxylic acid ester composition according to claim 1 or 2, wherein the average degree of esterification of the xylitol carboxylic acid ester is 1.0 to 4.

0.

4. The xylitol carboxylic acid ester composition according to claim 1 , wherein the carboxylic acid ester of xylitol comprises a monoester of xylitol, a diester of xylitol, and a triester of xylitol.

5. 5. The xylitol carboxylic acid ester composition according to claim 1, comprising 0.05% to 40% by weight of free xylitol.

6. 6. The xylitol carboxylic acid ester composition according to claim 1, comprising less than 25% by weight of at least one free carboxylic acid.

7. The xylitol carboxylic acid ester composition according to any one of claims 1 to 6, wherein the secondary ester positional isomer is contained in an amount of 5% by weight to 25% by weight of the total monoester components of the xylitol carboxylic acid ester.

8. The xylitol carboxylic acid ester composition according to any one of claims 1 to 7, wherein at least two positional isomers are contained in all monoester components of the xylitol carboxylic acid esters and in all diester components of the xylitol carboxylic acid esters.

9. A method for producing the xylitol carboxylic acid ester composition according to any one of claims 1 to 8, comprising: A) providing xylitol and at least one acyl donor; B) reacting xylitol with said at least one acyl donor in the presence of a lipase at a temperature between 75°C and 110°C to obtain a xylitol carboxylic acid ester composition; and optionally C) a process step of purifying the xylitol carboxylic acid ester composition. A method comprising:

10. 10. The method of claim 9, wherein process step A) comprises blending said xylitol and said at least one acyl donor for at least 10 minutes.

11. 11. The method according to claim 9 or 10, wherein the xylitol and the at least one acyl donor represent at least 80% by weight of the total reaction batch at the start of process step B).

12. The lipases include lipase derived from Thermomyces lanuginosus (accession number O59952), lipase A and B derived from Candida antarctica (accession number P41365), lipase derived from Mucor miehei (accession number P19515), lipase derived from Humicola sp. Lipases derived from Humicola sp. (accession number O59952), Rhizomucor javanicus (accession number S32492), Rhizopus oryzae (accession number P61872), Candida rugosa (accession numbers P20261, P32946, P32947, P3294, and P32949), Rhizopus niveus (accession number P61871), Penicillium camemberti (accession number P25234), Aspergillus niger (accession number P25235), and the like. niger lipases (ABG73613, ABG73614 and ABG37906) and Penicillium cyclopium lipase (Accession No. P61869), and those having at least 90% homology thereto at the amino acid level.

13. 13. The method according to claim 9, wherein process step B) is carried out at a pressure of less than 1 bar.

14. 9. Use of the xylitol carboxylic acid ester composition according to any one of claims 1 to 8 as a viscosity modifier, care active ingredient, foam booster or solubilizer, antibacterial agent, antistatic agent, binder, corrosion inhibitor, dispersant, emulsifier, film former, humectant, opacifier, oral care agent, preservative, skin care agent, hydrophilic emollient, foam stabilizer or non-ionic surfactant, or in a cleaning or care formulation.

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