Carboxymethyl trehalose methyl ester as well as preparation and application thereof

Abstract

The invention discloses carboxymethyl trehalose methyl ester as well as preparation and application thereof. The structural formula of the carboxymethyl trehalose methyl ester is as follows: # imgabs0 #. The preparation method comprises the following steps: by taking carboxymethyl trehalose and iodomethane as raw materials, preparing a carboxymethyl trehalose methyl ester compound through chemical substitution reaction under the conditions of catalysis and heating of a catalyst, and then preparing the carboxymethyl trehalose methyl ester extracting solution through extraction, filtration, thin layer chromatography separation, plate digging and extraction. Compared with carboxymethyl trehalose, the carboxymethyl trehalose methyl ester disclosed by the invention has the advantages that the molecular lipophilicity is obviously improved, and the carboxymethyl trehalose methyl ester can be better and widely applied to the industries of cosmetics, detergents and the like; the preparation method is simple in raw material source, free of special equipment and reagents, convenient to operate, easy in condition realization and good in application prospect.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and relates to carboxymethyl trehalose methyl ester, preparation thereof and application thereof. Background Art

[0002] Carboxymethyl trehalose has better moisture absorption capacity than trehalose at relative humidity of 43% and 81%, and also has better moisture absorption and moisturizing capacity than hyaluronic acid. Due to its low cost and easy synthesis, people prefer to use it to replace hyaluronic acid as a moisturizing and moisture-absorbing ingredient in cosmetic emollients. Therefore, carboxymethyl trehalose, as an oligosaccharide raw material, has a strong pioneering significance in the cosmetic field.

[0003] The oil-water partition coefficient (log P value) refers to the logarithmic value of the ratio of the partition coefficients of a chemical substance in n-octanol (oil) and water. The larger the log P value, the more lipophilic the chemical substance is, and the smaller the log P value, the more hydrophilic it is. The log P value of carboxymethyl trehalose is -4.86, showing strong hydrophilicity and better hydration ability. However, carboxymethyl trehalose has poor lipophilicity and cannot be dissolved in cosmetics with oily preparations, such as makeup remover oil, which limits the application of carboxymethyl trehalose in cosmetics.

[0004] There are few reports in domestic and foreign literature on how to improve the lipophilicity of carboxymethyl trehalose. In addition, the existing methyl ester preparation method has the problems of complex process flow, many side reactions, the methylation / methylesterification process needs to be completed in different reactors, the reaction process needs to be carried out under the catalysis of strong base or strong acid, high requirements on equipment materials, high cost, high pollution, numerous post-reaction treatment and purification steps, and easy emulsification in the extraction stage resulting in low product yield.

[0005] At present, there are very few research reports on carboxymethyl trehalose methyl ester. This patent abandons the synthesis technology of strong acid and strong base, and develops a simple and low-cost preparation method of carboxymethyl trehalose methyl ester based on green environmental protection to improve the lipophilicity of carboxymethyl trehalose. Summary of the invention

[0006] Due to the above defects in the prior art, the present invention provides a method for preparing carboxymethyl trehalose methyl ester to overcome the technical problems of lengthy process flow, high cost consumption and low product yield in the existing methyl ester preparation process and the problem of poor lipophilicity of current carboxymethyl trehalose.

[0007] In order to achieve the above object, the present invention provides the following technical solutions:

[0008] Carboxymethyl trehalose methyl ester has the following structural formula:

[0009] .

[0010] The log P value of the above carboxymethyl trehalose methyl ester is -1.34, which is greater than that of carboxymethyl trehalose. Compared with carboxymethyl trehalose, the lipophilicity of the molecule is significantly improved, and it can be widely used in the cosmetics, detergents and other industries.

[0011] The present invention provides a method for preparing the carboxymethyl trehalose methyl ester as described above. Carboxymethyl trehalose, methyl iodide and a transition metal catalyst are dissolved in a solvent and reacted. The reactants are subjected to high-temperature rotary evaporation to dryness to obtain a solid. After cooling to room temperature, the solid is extracted with an organic solvent. The extract is filtered, separated by thin layer chromatography, plated and extracted to obtain a carboxymethyl trehalose methyl ester extract.

[0012] The invention allows carboxymethyl trehalose to undergo a chemical substitution reaction with methyl iodide, so that the carboxymethyl trehalose molecule is connected to a methyl group, thereby generating carboxymethyl trehalose methyl ester. Compared with carboxymethyl trehalose, the lipophilicity of the carboxymethyl trehalose methyl ester is significantly improved, and the carboxymethyl trehalose methyl ester can be widely used in the cosmetics, detergent and other industries. The preparation method does not require special equipment and reagents, is simple to operate, and the reaction conditions are easy to achieve, so the application prospect is good.

[0013] As the preferred technical solution:

[0014] The carboxymethyl trehalose methyl ester extract obtained by the method described above is then vacuum evaporated to dryness to obtain carboxymethyl trehalose methyl ester solid.

[0015] In the method as described above, the molar ratio of carboxymethyl trehalose to methyl iodide is 1:2-5.

[0016] In the method as described above, the catalyst is a mixture of silver oxide, iron oxide and aluminum oxide in a mass ratio of 1 to 2:1:1;

[0017] The total mass of the catalyst is 1-10% of the mass of carboxymethyl trehalose. Carboxymethyl trehalose and methyl iodide undergo a chemical substitution reaction under the catalysis of silver oxide, iron oxide and aluminum oxide.

[0018] The method as described above, wherein the solvent is selected from one or more of dimethylformamide, dimethyl sulfoxide and tetrahydrofuran;

[0019] The mass ratio of the solvent to carboxymethyl trehalose is 1-2:1.

[0020] In the above method, the high-temperature rotary evaporation to dryness is carried out in an oil bath at a temperature of 130-150°C.

[0021] In the method as described above, the organic solvent used for leaching is acetonitrile, and the developing solvent used for thin layer chromatography is a mixture of dichloromethane, formic acid and water, and the volume ratio of dichloromethane, formic acid and water is 7:2:1;

[0022] The separation medium used in thin layer chromatography was silica gel.

[0023] The method as described above, the reaction temperature of the reaction is 30-50°C, and the reaction time is 5-29h;

[0024] The rotary evaporation of carboxymethyl trehalose methyl ester to dryness is carried out in a water bath at a temperature of 80-85°C.

[0025] In addition, the present invention also provides the use of the above-mentioned carboxymethyl trehalose methyl ester in the preparation of cosmetics or detergents.

[0026] The above technical solution is only a feasible technical solution of the present invention, and the protection scope of the present invention is not limited thereto. Those skilled in the art can reasonably adjust the specific design according to actual needs.

[0027] The above invention has the following advantages or beneficial effects:

[0028] (1) The log P value (-1.34) of the carboxymethyl trehalose methyl ester of the present invention is greater than that of carboxymethyl trehalose. Compared with carboxymethyl trehalose, the lipophilicity of the molecule is significantly improved, and it can be widely used in the cosmetics, detergents and other industries;

[0029] (2) The preparation method of carboxymethyl trehalose methyl ester of the present invention does not require special equipment and reagents, is simple to operate, and the reaction conditions are easy to achieve, and has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The present invention and its features, appearance and advantages will become more apparent by reading the detailed description of non-limiting embodiments with reference to the following drawings. The same reference numerals indicate the same parts in all the drawings. The drawings are not drawn to scale, and emphasis is placed on illustrating the subject matter of the present invention.

[0031] Figure 1 is the HPLC spectrum of carboxymethyl trehalose methyl ester;

[0032] Figure 2 is the HPLC spectrum of carboxymethyl trehalose;

[0033] Figure 3 is the Fourier transform infrared spectrum of carboxymethyl trehalose;

[0034] Figure 4 This is the Fourier transform infrared spectrum of carboxymethyl trehalose methyl ester. DETAILED DESCRIPTION

[0035] The structure of the present invention is further described below in conjunction with the accompanying drawings and specific embodiments, but is not intended to limit the present invention.

[0036] Example 1

[0037] Under stirring, 5 g of commercially available carboxymethyl trehalose (Shanghai Nonbenya Biotechnology Co., Ltd.) was dissolved in 5 g of dimethylformamide, and then 10 g of iodomethane was slowly added. After stirring evenly, 0.5 g of catalyst (a mixture of silver oxide, iron oxide and aluminum oxide in a mass ratio of 1:1:1) was added. The reaction temperature was controlled to 30°C. After stirring for 29 hours, the carboxymethyl trehalose was basically consumed as detected by TLC spot plate, and the reaction was stopped. The reactants were rotary evaporated in an oil bath at 140°C to dryness to obtain a solid. After the solid was cooled to room temperature, it was extracted with acetonitrile, insoluble matter was filtered out with filter paper, the filtrate was collected, and then the filtrate was vacuum dried and concentrated to obtain a concentrate, the concentrate was spotted on a thin layer chromatography silica gel preparation plate, and after chromatography with a developing agent (a mixture of dichloromethane, formic acid and water in a volume ratio of 7:2:1), the silica gel area containing carboxymethyl trehalose methyl ester was dug out, and the silica gel containing carboxymethyl trehalose methyl ester was extracted with acetonitrile, and then filtered and rotary evaporated in a water bath at 85°C to obtain carboxymethyl trehalose methyl ester solid, with a yield of 86.6%.

[0038] The HPLC spectrum and Fourier transform infrared spectrum of the obtained product are as follows: Figure 1 and 4 As shown, the HPLC spectrum and Fourier transform infrared spectrum of carboxymethyl trehalose are shown in Figure 2 and 3 As shown, from Figure 1 and Figure 2 From the comparison, it can be seen that the peak time of carboxymethyl trehalose methyl ester is 8.823min, and the peak shape of carboxymethyl trehalose methyl ester is single and the purity is high; Figure 3 and Figure 4 It can be seen from the comparison that carboxymethyl trehalose methyl ester has a wave number of 2257.5 cm -1 There is absorption, while carboxymethyl trehalose does not have this absorption peak, that is, the prepared product is different from carboxymethyl trehalose.

[0039] Example 2

[0040] Under stirring, 5 g of commercially available carboxymethyl trehalose (Shanghai Nonbenya Biotechnology Co., Ltd.) was dissolved in 9 g of dimethyl sulfoxide, and then 15 g of iodomethane was slowly added. After stirring evenly, 0.2 g of catalyst (a mixture of silver oxide, iron oxide and aluminum oxide in a mass ratio of 1.5:1:1) was added. The reaction temperature was controlled to 40°C. After stirring and reacting for 20 hours, the carboxymethyl trehalose was basically consumed as detected by TLC spot plate, and the reaction was stopped. The reactants were rotary evaporated in a 130°C oil bath to dryness to obtain a solid. After the solid was cooled to room temperature, it was extracted with acetonitrile, insoluble matter was filtered out with filter paper, the filtrate was collected, and then the filtrate was vacuum dried and concentrated to obtain a concentrate, the concentrate was spotted on a thin layer chromatography silica gel preparation plate, and after chromatography with a developing agent (a mixture of dichloromethane, formic acid and water in a volume ratio of 7:2:1), the silica gel area containing carboxymethyl trehalose methyl ester was dug out, and the silica gel containing carboxymethyl trehalose methyl ester was extracted with acetonitrile, and then filtered and rotary evaporated in a water bath at 82°C to obtain carboxymethyl trehalose methyl ester solid with a yield of 89.3%.

[0041] Example 3

[0042] Under stirring, 5 g of commercially available carboxymethyl trehalose (Shanghai Nonbenya Biotechnology Co., Ltd.) was dissolved in 10 g of tetrahydrofuran, and then 25 g of iodomethane was slowly added. After stirring evenly, 0.05 g of catalyst (a mixture of silver oxide, iron oxide and aluminum oxide in a mass ratio of 2:1:1) was added. The reaction temperature was controlled to 50°C. After stirring and reacting for 5 hours, the carboxymethyl trehalose was basically consumed as detected by TLC spot plate, and the reaction was stopped. The reactants were rotary evaporated in a 150°C oil bath to dryness to obtain a solid. After the solid was cooled to room temperature, it was extracted with acetonitrile, insoluble matter was filtered out with filter paper, the filtrate was collected, and then the filtrate was vacuum dried and concentrated to obtain a concentrate, the concentrate was spotted on a thin layer chromatography silica gel preparation plate, and after chromatography with a developing agent (a mixture of dichloromethane, formic acid and water in a volume ratio of 7:2:1), the silica gel area containing carboxymethyl trehalose methyl ester was dug out, and the silica gel containing carboxymethyl trehalose methyl ester was extracted with acetonitrile, and then filtered and rotary evaporated in a water bath at 80°C to obtain carboxymethyl trehalose methyl ester solid, with a yield of 90.6%.

[0043] Comparative Example 1

[0044] Under stirring, 5g of commercially available carboxymethyl trehalose (Shanghai Nongbenya Biotechnology Co., Ltd.) was dissolved in 9g of dimethylformamide, and then 15g of iodomethane was slowly added. After stirring evenly, the reaction temperature was controlled to 40°C. After stirring and reacting for 20 hours, the carboxymethyl trehalose was basically consumed by TLC spot plate detection, and the reaction was stopped. The reactant was rotary evaporated to dryness in a 140°C oil bath to obtain a solid. After the solid was cooled to room temperature, it was extracted with acetonitrile, the insoluble matter was filtered out with filter paper, and the filtrate was collected. The filtrate was then vacuum dried and concentrated to obtain a concentrate, and the concentrate was applied to a thin layer chromatography silica gel preparation plate. After chromatography with a developing agent (a mixture of dichloromethane, formic acid and water in a volume ratio of 7:2:1), the silica gel area containing carboxymethyl trehalose methyl ester was dug, and the silica gel containing carboxymethyl trehalose methyl ester was extracted with acetonitrile, and then filtered and rotary evaporated in a water bath at 82°C to obtain carboxymethyl trehalose methyl ester solid, with a yield of 44.3%.

[0045] By comparing Example 2 and Comparative Example 1, it can be seen that the lack of catalyst has a great influence on the product yield. The reaction system of Comparative Example 1 lacks a catalyst and cannot reduce the activation energy of the reaction, so that the reaction cannot be accelerated, resulting in a reduced yield.

[0046] Comparative Example 2

[0047] Under stirring, 5 g of commercially available carboxymethyl trehalose (Shanghai Nonbenya Biotechnology Co., Ltd.) was dissolved in 9 g of dimethylformamide, and then 15 g of iodomethane was slowly added. After stirring evenly, 0.2 g of catalyst (a mixture of silver oxide, iron oxide and aluminum oxide in a mass ratio of 1.5:1:1) was added. The reaction temperature was controlled to 20°C. After stirring and reacting for 20 hours, the carboxymethyl trehalose was basically consumed as detected by TLC spot plate, and the reaction was stopped. The reactants were rotary evaporated in a 140°C oil bath to dryness to obtain a solid. After the solid was cooled to room temperature, it was extracted with acetonitrile, insoluble matter was filtered out with filter paper, the filtrate was collected, and then the filtrate was vacuum dried and concentrated to obtain a concentrate, the concentrate was spotted on a thin layer chromatography silica gel preparation plate, and after chromatography with a developing agent (a mixture of dichloromethane, formic acid and water in a volume ratio of 7:2:1), the silica gel area containing carboxymethyl trehalose methyl ester was dug out, and the silica gel containing carboxymethyl trehalose methyl ester was extracted with acetonitrile, and then filtered and rotary evaporated in a water bath at 82°C to obtain carboxymethyl trehalose methyl ester solid with a yield of 50.7%.

[0048] By comparing Example 2 and Comparative Example 2, it can be seen that the reaction temperature has a great influence on the product yield. The reaction temperature of Comparative Example 2 is lower than that of Example 2. After the temperature is lowered, the energy of the reactant molecules will also decrease, the number of activated molecules will decrease, and the number of effective collisions will decrease, thereby reducing the chemical reaction rate. In addition, when the temperature is low, the activity of the catalyst will also be affected, ultimately leading to a decrease in the yield.

[0049] Those skilled in the art should understand that those skilled in the art can implement variations by combining the prior art and the above embodiments, which will not be described in detail here. Such variations do not affect the essential content of the present invention, and will not be described in detail here.

[0050] The above describes the preferred embodiments of the present invention. It should be understood that the present invention is not limited to the above-mentioned specific embodiments, and the devices and structures that are not described in detail should be understood to be implemented in a common manner in the art; any technician familiar with the art can use the above-disclosed methods and technical contents to make many possible changes and modifications to the technical solutions of the present invention without departing from the scope of the technical solutions of the present invention, or modify them into equivalent embodiments of equivalent changes, which does not affect the essential content of the present invention. Therefore, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solutions of the present invention are still within the scope of protection of the technical solutions of the present invention.

Claims

1. Carboxymethyl trehalose methyl ester, characterized in that: Its structural formula is as follows: 。 2. The method for preparing carboxymethyl trehalose methyl ester according to claim 1, characterized in that: Carboxymethyl trehalose, iodomethane and a transition metal catalyst are dissolved in a solvent and reacted, and the reactants are rotary evaporated to dryness at high temperature to obtain a solid. After cooling to room temperature, the solid is extracted, filtered, separated by thin layer chromatography, scooped and extracted to obtain a carboxymethyl trehalose methyl ester extract.

3. The method according to claim 2, characterized in that The obtained carboxymethyl trehalose methyl ester extract is then vacuum-evaporated to dryness to obtain carboxymethyl trehalose methyl ester solid.

4. The method according to claim 2, characterized in that: The molar ratio of the carboxymethyl trehalose to methyl iodide is 1:2-5.

5. The method according to claim 2, characterized in that: The catalyst is a mixture of silver oxide, iron oxide and aluminum oxide in a mass ratio of 1 to 2:1:1; The total mass of the catalyst is 1-10% of the mass of carboxymethyl trehalose.

6. The method according to claim 2, characterized in that The solvent is selected from the group consisting of dimethylformamide, dimethyl sulfoxide and tetrahydrofuran; The mass ratio of the solvent to carboxymethyl trehalose is 1-2:

1.

7. The method according to claim 2, characterized in that The high-temperature rotary evaporation to dryness is carried out in an oil bath pot at a temperature of 130-150°C.

8. The method according to claim 2, characterized in that: The organic solvent used for extraction was acetonitrile, and the developing solvent used for thin layer chromatography was a mixture of dichloromethane, formic acid and water, with the volume ratio of dichloromethane, formic acid and water being 7:2:1; The separation medium used in thin layer chromatography was silica gel.

9. The method according to claim 3, characterized in that: The reaction temperature of the reaction is 30-50°C, and the reaction time is 5-29h; The rotary evaporation of carboxymethyl trehalose methyl ester to dryness is carried out in a water bath at a temperature of 80-85°C.

10. Use of the carboxymethyl trehalose methyl ester according to claim 1 in the preparation of cosmetics or detergents.

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