Glycosyl barbiturates

Abstract

The present invention relates to a gelling agent comprising a saccharide having general formula (I), in which - Sacc is in pyranose and / or furanose form and represents a monosaccharide or polysaccharide containing up to 20 saccharide units of the L and / or D series, said monosaccharide or polysaccharide having at least one free hydroxyl function, - X1 + is Na + , Li + , K + , + NR 3 R 4 R 5 R 6 , and R 7 -NH3 + R may be the same or different and represent a cation selected from the group consisting of 3 , R 4 , R 5 , and R 6 is (C1~C 20 ) represents an alkyl group, R 7 is (C1~C 20 ) alkyl group, optionally containing at least one unsaturation, said alkyl group optionally containing at least one (C6-C 10 ) substituted with an aryl group, - R 2 represents in particular H or methyl] and compounds having tautomeric forms thereof. JPEG2025502441000016.jpg33170

Description

[Technical field]

[0001] The object of the present invention is a novel gelling agent based on glycosyl barbiturates, known by the scientific name β-C-glycoside pyrimidinetrione, and a method for the preparation of organogels or oleogels by use of said gelling agent based on glycosyl barbiturates. [Background technology]

[0002] Organogelators are small organic molecules that are capable of texturing and even gelling all kinds of organic solvents or oil phases, even at relatively low mass concentrations (less than 1% by weight).

[0003] Currently, there are a large number of molecules that can be used as organogelators, but these have certain drawbacks.

[0004] This is because the synthesis of these organogelators requires multiple steps and the use of toxic solvents and / or reagents. Furthermore, the majority of these organogelators are hydrophobic and therefore insoluble in aqueous media and therefore are not "washable". For many organogelators, their chemical and enzymatic stability is an obstacle to their development.

[0005] Moreover, polymeric organogelators, such as ethyl cellulose, have the additional drawback of leaving a film after application.

[0006] Finally, organogelators are often application specific, that is, they have only a single function: texturing or gelling. [Prior art documents] [Non-patent literature]

[0007] [Non-Patent Document 1] Gonzales MA et al., Carbohydrate Research 1986, 158, pp. 58-66. [Non-Patent Document 2] Wulff G. et al., Carbohydrate Research 1994, 257, pp. 81-95. Summary of the Invention [Problem to be solved by the invention]

[0008] Therefore, there is currently a need for organogelators that do not have the aforementioned drawbacks, and therefore in particular to provide organogelating compounds that can be easily synthesized in an environmentally friendly manner, are chemically and enzymatically stable, and are bioavailable.

[0009] It is therefore a goal of the present invention to provide organogelators that can be synthesized in a single step and are easy to purify in quantitative yields under environmentally friendly conditions, especially in the presence of aqueous solvents, without the formation of by-products.

[0010] Another goal of the present invention is to provide organogelators that are completely soluble in water and therefore washable at the end of application, e.g., skin treatment.

[0011] Another goal of the present invention is to provide organogelators that are chemically and enzymatically stable and, optionally, have easily tunable gelling capabilities. [Means for solving the problem]

[0012] Thus, the present invention provides a gelling or texturing agent comprising a compound of the following general formula (I):

[0013] [ka]

[0014] [In the formula, - Sacc denotes a monosaccharide or polysaccharide containing up to 20 saccharide units, in pyranose and / or furanose form, of the L and / or D series, said monosaccharide or polysaccharide having at least one free hydroxyl function, - X1 + is Na + , Li + , K + , + NR 3 R 4 R 5 R 6 , R 7 -NH3 + , + PR 3 R 4 R 5 R 6 , and + S.R. 3 R 4 R 5 represents a cation selected from the group consisting of Same or different R 3 , R 4 , R 5 , and R 6 Optionally contains at least one unsaturation (C1 to C 20 ) alkyl group, wherein the alkyl group optionally has at least one (C6-C 10 ) substituted with aryl groups, in particular phenyl groups, R 7 Optionally contains at least one unsaturation (C1 to C 20 ) alkyl group, wherein the alkyl group optionally has at least one (C6-C 10 ) substituted with aryl groups, in particular phenyl groups, - R 2 is H, methyl or optionally contains at least one unsaturation (C1-C 20 ) alkyl group, wherein the alkyl group optionally has at least one (C6-C 10 ) substituted with aryl groups, especially phenyl groups] and the use of compounds having tautomeric forms thereof. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] Thus, the compounds used as texturing or gelling agents (or organogelators) according to the present invention are C-glycoside derivatives which are chemically and enzymatically stable due to the non-natural C-glycosidic bond.

[0016] The gelling ability of these compounds can be easily adjusted by influencing their concentration and the nature of the cationic counterion, for example by simple mixing.

[0017] The organogelators according to the invention can be used, for example, in cosmetic compositions and perfumes, or in pharmaceutical or dermopharmaceutical compositions, but also in the food sector, or as lubricants, paints or in the construction industry, or for maintaining painting canvases.

[0018] Texturizing agents are additives present in cosmetic, food, or other formulations to increase the consistency, viscosity, and sensory properties of the final product. Texturizing agents are especially synthetic polymers such as polyacrylates, biosourced polymers such as polysaccharides and their derivatives, gums, and lipids derived from oils or butters, esters, or waxes.

[0019] A gelling agent may be texturizing, which will depend on its concentration in the medium: below its minimum gelling concentration for a given fatty phase it will be texturizing, above or equal to it it will be gelling.

[0020] Tautomeric forms of general formula (I) are as follows:

[0021] [ka]

[0022] According to the present invention, (C t ~C z) group means a group comprising a carbon chain which may have t to z carbon atoms, for example a carbon chain C1 to C6 which may have 1 to 6 carbon atoms.

[0023] According to the present invention, the term "alkyl", unless stated to the contrary, denotes a linear or branched saturated hydrocarbon aliphatic group containing from 1 to 20 carbon atoms. By way of example, mention may be made of the methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, tert-butyl or pentyl groups.

[0024] According to one embodiment, the alkyl groups according to the invention may be interrupted by at least one unsaturation.

[0025] The alkyl groups of this invention can also be substituted with at least one aryl group.

[0026] According to the invention, an aryl group is a cyclic aromatic group containing between 6 and 10 carbon atoms. By way of example of aryl groups, mention may be made of the phenyl or naphthyl groups.

[0027] Preferably, in formula (I), identical or different R 3 , R 4 , R 5 , and R 6 is (C1~C 20 ) represents an alkyl group or a benzyl group.

[0028] Preferably, in formula (I), R 7 is (C1~C 20 ) represents an alkyl group.

[0029] Preferably, in formula (I), R 2 represents H or methyl, preferably methyl.

[0030] Preferably, in formula (I), X1 + is Na + , Li + , and K+ represents a cation selected from the group consisting of, preferentially Na + It is.

[0031] In one embodiment, the cation X + can be selected from multiply charged derivatives such as, for example, polyammonium ions.

[0032] In one embodiment, in formula (I), Sacc is selected from the group consisting of D-glucose, D-galactose, D-mannose, D-xylose, D-lyxose, L-fucose, L-arabinose, L-rhamnose, D-glucuronic acid, D-galacturonic acid, D-iduronic acid, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, D-maltose, D-lactose, D-cellobiose, D-maltotriose, D-galactosamine, D-glucosamine, N-acetyl-D-galactosamine, or N-acetyl-D-glucosamine, D-iduronic acid, D-glucuronic acid, xylobiose, and oligomers thereof (from xylotriose to xylohexaose).

[0033] Preferably, in formula (I), Sacc is D-glucose.

[0034] The C-glycoside derivatives having formula (I) according to the invention can be prepared, for example, according to the methods described by Gonzales MA et al., Carbohydrate Research 1986, 158, 58-66, and by Wulff G. et al., Carbohydrate Research 1994, 257, 81-95.

[0035] Among the C-glycoside derivatives having formula (I) that can be used according to the invention are the following compounds: - Sodium 1,3-dimethyl-2,6-dioxo-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxy-methyl)tetrahydro-2H-pyran-2-yl]-1,2,3,6-tetrahydropyrimidin-4-olate:

[0036] [ka]

[0037] - Sodium 2,6-dioxo-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]-1,2,3,6-tetrahydropyrimidin-4-olate

[0038] [ka]

[0039] - Sodium 1,3-dimethyl-2,6-dioxo-5-[(2S,3R,4R,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]-1,2,3,6-tetrahydropyrimidin-4-olate:

[0040] [ka]

[0041] - Sodium 1,3-dimethyl-2,6-dioxo-5[(2S,3R,4S,5R)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl]-1,2,3,6-tetrahydropyrimidin-4-olate:

[0042] [ka]

[0043] - Sodium 2,6-dioxo-5-[(2S,3R,4S,5R)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl]-1,2,3,6-tetrahydropyrimidin-4-olate

[0044] [ka]

[0045] - Sodium 1,3-dimethyl-2,6-dioxo-5-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-methyl-tetrahydro-2H-pyran-2-yl]-1,2,3,6-tetrahydropyrimidin-4-olate:

[0046] [ka]

[0047] is particularly preferred.

[0048] Preferably, the compound having formula (I) according to the invention has the formula

[0049] [ka]

[0050] Follow.

[0051] Several advantages are associated with the use of this class of molecules belonging to the C-glycoside family.

[0052] Said preferred glycosyl barbiturates are, for example, obtained in a single synthetic step in water and are characterized by a glucose unit linked to N,N-dimethylbarbituric acid by a C-glycosidic bond. Its purification is obtained by simple precipitation of the reaction medium in quantitative yield, making its production easy and practical from an industrial point of view.

[0053] The starting reagents for preparing this molecule are commercially available.

[0054] The compounds (or glyco-gelators) of the present invention texturize both organic solvents and oils of different polarities to gelation, and their gelling ability can be easily tuned by the nature of the associated cationic counterion. Gelation can be induced by ultrasound, simple mixing, or by a heating cycle followed by a cooling cycle to room temperature, as explained below.

[0055] According to one embodiment, the compound having formula (I) is used as a gelling agent for an organic liquid or mixture of liquids, said organic liquid being chosen from organic solvents and oils.

[0056] According to the present invention, an organic liquid is a liquid having or containing a carbon chain. As indicated above, it may be an organic solvent, an oil, or a mixture thereof.

[0057] According to one embodiment, the organic liquid is an organic solvent selected from the group consisting of alcohols, ketones, aliphatic, aromatic or halogenated hydrocarbons, esters, nitrogen derivatives, ethers, silicones, aliphatic carboxylic acids and their ester derivatives, amides, lipids or glycerides. Preferably, the organic solvent is selected from ethanol, propanol, glycerol, butanol, octanol, isopropanol, anisole, octyldodecanol, ethyl acetate, acetone, tetrahydrofuran, oleic acid, linoleic acid, palmitic acid and esters of adipic acid, stearic acid or capric acid.

[0058] According to one embodiment, the organic liquid is an oil selected from vegetable or animal oils and natural or synthetic mineral oils.Preferably, the oil is selected from rapeseed oil, castor oil, jojoba oil, lavender essential oil, palm oil, olive oil, sunflower oil, paraffin or liquefied petroleum.

[0059] Preferably, the organic liquid is an organic solvent selected from ethanol, propanol, butanol, glycerol, octanol, isopropanol, anisole, ethyl acetate, and tetrahydrofuran, or an oil selected from rapeseed oil, or lavender essential oil (lavender EO).

[0060] The present invention also relates to the aforementioned uses, wherein the compound having formula (I) is used as an agent for texturing or gelling a mixture of an organic liquid, preferably comprising at least one oil and / or at least one organic solvent.

[0061] For example, as mixtures, mention may be made of a mixture comprising lavender essential oil and ethanol, or a mixture comprising rapeseed oil, octanol, and isopropanol, or a silicone oil and a fatty ester, but also of mixtures of two organic solvents, such as a mixture of octanol and ethanol.

[0062] Preferably, in the context of the use as defined above, the proportion by weight of the compound having formula (I) is between 0.1% and 10% by weight, preferably 1% to 5% by weight, relative to the weight of the organic liquid or mixture of organic liquids.

[0063] The present invention also relates to a method for preparing an organogel or oleogel comprising the step of placing a compound having formula (I) in the presence of an organic liquid or a mixture of organic liquids, said liquids being selected from organic solvents and oils and as defined above, The compound having the formula (I) is represented by the following formula:

[0064] [ka]

[0065] [In the formula, - Sacc denotes a monosaccharide or polysaccharide containing up to 20 saccharide units, in pyranose and / or furanose form, of the L and / or D series, said monosaccharide or polysaccharide having at least one free hydroxyl function, - X1 + is Na + , Li + , K + , + NR 3 R 4 R 5 R 6 , R 7 -NH3 + , + PR 3 R 4 R 5 R 6 , and + S.R. 3 R 4 R 5 represents a cation selected from the group consisting of Same or different R 3 , R 4 , R 5 , and R 6 Optionally contains at least one unsaturation (C1 to C 20 ) alkyl group, wherein the alkyl group optionally has at least one (C6-C 10 ) substituted with aryl groups, in particular phenyl groups, R 7 Optionally contains at least one unsaturation (C1 to C 20 ) alkyl group, wherein the alkyl group optionally has at least one (C6-C 10 ) substituted with aryl groups, in particular phenyl groups, - R 2 is H, methyl or optionally contains at least one unsaturation (C1-C 20 ) alkyl group, wherein the alkyl group optionally has at least one (C6-C 10 ) substituted with an aryl group, particularly a phenyl group] and tautomeric forms thereof.

[0066] According to the present invention, the term organogel refers to a gel of an organic solvent and the term oleogel refers to a gelled oil.

[0067] According to one embodiment, the method of the present invention comprises the step of adding to an organic liquid or mixture of organic liquids an aqueous solution of a compound having formula (I).

[0068] Preferably, the adding step further comprises the steps of sonication, or heating or cooling the organic liquid or mixture of organic liquids.

[0069] According to one embodiment of the method according to the invention, the organic liquid or mixture of organic liquids comprises an additional compound selected from dyes or pigments, opacifiers, organic or mineral UV filters, odorant molecules, and pharmaceutical active ingredients, such as Nile red, carmine red, metal oxides, ethylhexyl triazone, eucalyptol, or doxorubicin. EXAMPLES

[0070] Example 1: Determination of the appropriate dose to form a 2% gel (w / v) Weigh 10 mg of glucosyl barbiturate or sodium β-C-glucoside pyrimidinetrione in a flask of about 1.5 ml with a screw stopper. Add 450 μL of the chosen solvent and then sonicate the mixture for a few seconds to disperse the powder well in the solvent (in most cases glucosyl barbiturate is not soluble in the solvent). Next, add 2 μL of water in increments, sonicate the mixture between each addition, and gently stir by hand to see if a gel has formed. The duration of sonication varies depending on the nature of the solvent. Once the gel has formed, it cannot be made very homogenous. In this case, you need to be able to determine what action to take to get a gel. Often it is necessary to either i) add a very small amount of water, heat, let it stand and cool, or ii) heat, let it stand while sonicating and cool (if glucosyl barbiturate precipitates during cooling). The mixture is then completed with the solvent and gelled to 500 μL.

[0071] Example 2: Formation of a gel by adding a mixture of solvent + water to glycobarbituric acid powder Weigh out 10 mg of sodium glucosyl barbiturate, then add a mixture of solvent and water in the proper proportions defined above in Example 1. The mixture is then sonicated at low temperature in an ultrasonic bath, or heated and left to cool to obtain a gel, or stirred quickly at room temperature and then left to settle.

[0072] For example, it is necessary to add 40 μL of water to 500 μL of ethanol, 60 μL of water to 440 μL of isopropanol, 45 μL of water to 455 μL of butanol, 60 μL of water to 420 μL of acetone, or 35 μL of water to 480 μL of propan-1-ol.

[0073] Example 3: Formation of a gel by adding a concentrated solution of sodium glucosyl barbiturate to a solvent The solvent is placed in a vessel under stirring, then an aqueous solution of sodium glucosyl barbiturate (1.47 M) is added in the proportions defined above in Example 1. The mixture is stirred for a few seconds, then stirring is stopped to allow the formation of a gel.

[0074] In this example, 80 μL of an aqueous solution of sodium glucosyl barbiturate (1.47 M) was added to 1 ml of 96% ethanol.

[0075] Example 4: Formation of gels using oils or non-polar solvents (e.g. rapeseed oil, toluene, anisole, etc.) When using a solvent that is not miscible with water, it is necessary to add any other solvent that allows the introduction of a small amount of water to form a gel (example of a mixture that can accept a small amount of water without forming two phases: lavender EO / ethanol), i.e. to change the nature of the counterion at the origin of sodium by an ammonium alkyl salt. Three ammonium salts were tested: cetyltrimethylammonium bromide (CTAB), tetrabutylammonium bromide (TBAB), or Tequat® LC 90i (tallow ester quat). To find favorable conditions for gelation, it is possible to use the same method as described in Example 1. Before adding the solvent and adjusting the appropriate amount of water, glucosyl barbiturate and the equivalent amount of ammonium salt are weighed out.

[0076] The various results are set forth below in Table 1 below.

[0077] For example, 10 mg of sodium glucosyl barbiturate was mixed with either 9.4 mg of TBAB or 11 mg of CTAB. Next, 400 μL of rapeseed oil was added, then the whole was sonicated for dispersion, and finally 5 μL of water was added. The sonication allowed the gel to form instantly.

[0078] The protocol followed for testing the various solvents in Table 1, with 10 mg of sodium glucosyl barbiturate weighed in each case, and 1 molar equivalent of ammonium salt, is that detailed in Example 4.

[0079] [Table 1A]

[0080] [Table 1B]

Claims

1. As an agent for texturing or gelling an organic liquid or a mixture of organic liquids, 【Chemistry 1】 [In the formula, Sacc stands for monosaccharides or polysaccharides containing up to 20 saccharide units, in pyranose and / or furanose form, of the L and / or D series, said monosaccharides or polysaccharides having at least one free hydroxyl function, X 1 + is Na + , Li + , K + , + NR 3 R 4 R 5 R 6 , R 7 -NH 3 + , + PR 3 R 4 R 5 R 6 , and + S.R. 3 R 4 R 5 represents a cation selected from the group consisting of Same or different R 3 , R 4 , R 5 , and R 6 optionally contains at least one unsaturation (C 1 ~C 20 ) alkyl group, said alkyl group optionally having at least one (C 6 ~C 10 ) substituted with an aryl group; R 7 optionally contains at least one unsaturation (C 1 ~C 20 ) alkyl group, said alkyl group optionally having at least one (C 6 ~C 10 ) substituted with an aryl group; R 2 H or optionally contains at least one unsaturation (C 1 ~C 20 ) alkyl group, said alkyl group optionally having at least one (C 6 ~C 10 ) substituted with an aryl group] and the use of compounds having tautomeric forms thereof.

2. 2. The use according to claim 1, wherein in formula (I), Sacc is selected from the group consisting of D-glucose, D-galactose, D-mannose, D-xylose, D-lyxose, L-fucose, L-arabinose, L-rhamnose, D-glucuronic acid, D-galacturonic acid, D-iduronic acid, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, D-maltose, D-lactose, D-cellobiose, D-maltotriose, D-galactosamine, D-glucosamine, N-acetyl-D-galactosamine, or N-acetyl-D-glucosamine, D-iduronic acid, D-glucuronic acid, xylobiose, and oligomers thereof with a hexosamine selected from D-glucose, D-galactose, D-mannose, D-xylobiose, and oligomers thereof.

3. 3. The use according to claim 1 or 2, wherein the organic liquid is selected from organic solvents and oils.

4. 4. The use according to claim 3, wherein the organic liquid is an organic solvent selected from the group consisting of alcohols, ketones, aliphatic, aromatic or halogenated hydrocarbons, esters, nitrogen derivatives, ethers, silicones, aliphatic carboxylic acids and their ester derivatives, amides, lipids or glycerides, preferably selected from ethanol, propanol, glycerol, butanol, octanol, isopropanol, anisole, ethyl acetate, octyldodecanol, tetrahydrofuran, acetone, oleic acid, linoleic acid, palmitic acid and esters of adipic acid, stearic acid or capric acid.

5. 5. Use according to claim 4, wherein the oil is selected from vegetable or animal oils and natural or synthetic mineral oils, preferably rapeseed oil, lavender essential oil, palm oil, olive oil, sunflower oil, castor oil, jojoba oil, paraffin or liquefied petroleum.

6. Use according to claims 1 to 5, in which the proportion by weight of the compound having formula (I) is between 0.1% and 10% by weight, preferably from 1% to 5% by weight, relative to the weight of the organic liquid or mixture of organic liquids.

7. A process for preparing an organogel or oleogel comprising the step of placing a compound having formula (I) in the presence of an organic liquid or a mixture of organic liquids, said liquids being selected from organic solvents and oils and as defined above, The compound having the formula (I) is represented by the following formula: 【Chemistry 2】 [In the formula, Sacc stands for monosaccharides or polysaccharides containing up to 20 saccharide units, in pyranose and / or furanose form, of the L and / or D series, said monosaccharides or polysaccharides having at least one free hydroxyl function, X 1 + is Na + , Li + , K + , + NR 3 R 4 R 5 R 6 , R 7 -NH 3 + , + PR 3 R 4 R 5 R 6 , and + S.R. 3 R 4 R 5 represents a cation selected from the group consisting of Same or different R 3 , R 4 , R 5 , and R 6 optionally contains at least one unsaturation (C 1 ~C 20 ) alkyl group, said alkyl group optionally having at least one (C 6 ~C 10 ) substituted with aryl groups, in particular phenyl groups, R 7 optionally contains at least one unsaturation (C 1 ~C 20 ) alkyl group, said alkyl group optionally having at least one (C 6 ~C 10 ) substituted with aryl groups, in particular phenyl groups, R 2 H or optionally contains at least one unsaturation (C 1 ~C 20 ) alkyl group, said alkyl group optionally having at least one (C 6 ~C 10 ) substituted with aryl groups, particularly phenyl groups] and tautomeric forms thereof.

8. 8. The method of claim 7, comprising adding to the organic liquid or mixture of organic liquids an aqueous solution of the compound having formula (I).

9. 9. The method of claim 8, wherein the adding step further comprises a step of treating with ultrasound, or a step of heating or cooling the organic liquid or mixture of organic liquids.

10. 10. The method according to any one of claims 7 to 9, wherein the organic liquid or mixture of organic liquids comprises additional compounds selected from dyes, odorant molecules and pharmaceutical active ingredients.

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