A preparation method of hydroxypropyltetrahydropyrantriol

Abstract

The present invention relates to a method for preparing hydroxypropyltetrahydropyrantriol, belonging to the technical field of fine chemicals. The method uses D-xylose as the starting material, first reacts with acetylacetone to obtain acetonyltetrahydropyrantriol, and then undergoes a carbonyl reduction reaction in the presence of an inexpensive catalyst to obtain hydroxypropylpyrantriol with an S configuration:R configuration = 50:50 to 55:45. Compared with the prior art, the technical solution of the present invention uses an inexpensive catalyst to replace the expensive ruthenium-carbon catalyst, significantly reducing the cost. At the same time, the prepared boswellic acid product has an S configuration:R configuration = 50:50 to 55:45, meeting the market's expectation for enhancing the physiological activity of boswellic acid.

Description

Technical Field

[0001] The present invention relates to the technical field of fine chemicals, and particularly relates to a preparation method of hydroxypropyltetrahydropyrantriol. Background Art

[0002] Boschniakine (Pro-Xylane), also known as hydroxypropyltetrahydropyrantriol, is a xylose derivative with anti-aging active substances. It can promote the production of glycosaminoglycans (GAGs), and then promote the production of proteoglycans. At the same time, Boschniakine can effectively promote the tight connection between the epidermis and the dermis, better fix the dermis layer, make the skin stronger and more elastic. Long-term use can improve neck fine lines and prevent aging.

[0003] L'Oréal, the original research company of Boschniakine, reported a method for preparing hydroxypropyltetrahydropyrantriol using ruthenium-carbon catalyst in the literature Bioorganic&Medicinal Chemistry Letters 19(2009)845–849, and obtained a product with de = 0. However, according to the report of Di Leiqin et al. in the literature "Deciphering the 'Black Box' of L'Oréal's 'Boschniakine'", they analyzed L'Oréal's Boschniakine product in detail and found that the ratio of S configuration:R configuration = 47:53, which is inconsistent with de = 0 in the aforementioned literature. Therefore, we carried out experiments using L'Oréal's scheme, and the results obtained were consistent with those published by Di Leiqin et al., that is, the configuration ratio is S configuration:R configuration = 47:53.

[0004] However, as is well known, the S configuration has better physiological activity than the R configuration. Therefore, there is still room for improvement in the activity of L'Oréal products on the market at present. At the same time, the expensive ruthenium-carbon catalyst is also an important reason for the high cost of the product.

[0005] Therefore, it is still necessary to study the preparation method of hydroxypropyltetrahydropyrantriol to solve the problems of high production cost and low physiological activity of Boschniakine products. Summary of the Invention

[0006] Aiming at the technical problems of high production cost and low physiological activity of Boschniakine products existing in the prior art, the present invention uses D-xylose (Compound 1) as the starting material, first reacts with acetylacetone (Step 1) to obtain acetonyltetrahydropyrantriol (Compound 2), and then carries out a carbonyl reduction reaction in the presence of an inexpensive catalyst to obtain hydroxypropylpyrantriol with a ratio of S configuration:R configuration = 50:50 to 55:45.

[0007] To solve the above technical problems, the present invention adopts the following technical solutions:

[0008] The present invention provides a method for preparing propylpyranetriol, comprising: reacting D-xylose (Compound 1) with acetylacetone (Step 1) to obtain acetonyltetrahydropyranetriol (Compound 2); then performing a carbonyl reduction reaction in the presence of a catalyst to obtain propylpyranetriol; the reaction process is as shown below:

[0009]

[0010] A method for preparing propylpyranetriol, the specific steps are as follows:

[0011] 1) React D-xylose (i.e., Compound 1) with acetylacetone to obtain acetonyltetrahydropyranetriol (i.e., Compound 2);

[0012] 2) In the presence of a catalyst, acetonyltetrahydropyranetriol reacts with hydrogen in a carbonyl reduction reaction to obtain propylpyranetriol (i.e., Compound 3).

[0013] In Step 1), the reaction solvent is selected from one of methanol, water, ethanol, tetrahydrofuran, isopropanol, and 1,4-dioxane. Preferably, in Step 1), the reaction solvent is water.

[0014] In Step 1), a base can be further added for the reaction, and the base is selected from at least one of sodium hydroxide, potassium hydroxide, sodium bicarbonate, and sodium carbonate.

[0015] In Step 1), the molar ratio of acetylacetone to Compound 1 is 1:1 to 3:1. Preferably, the molar ratio of acetylacetone to Compound 1 is 1:1.2 to 2.5:1. More preferably, the molar ratio of acetylacetone to Compound 1 is 1:1.5, 1:1.8, 1:2, 1:2.4.

[0016] The reaction temperature in Step 1) is 0°C - 80°C. Preferably, the reaction temperature in Step 1) is 5°C to 60°C. More preferably, the reaction temperature in Step 1) is 25°C.

[0017] The reaction time in Step 1) is 30 min to 10 h. Preferably, the reaction time in Step 1) is 1 h to 8 h. More preferably, the reaction time in Step 1) is 4 h.

[0018] Step 1) may further include post-treatment: extracting and separating with dichloromethane, collecting the aqueous phase, and concentrating under reduced pressure.

[0019] In Step 2), the catalyst is a nickel-carbon catalyst. Preferably, in Step 2), the catalyst is a 10% nickel-carbon catalyst.

[0020] The reaction in step 2) is carried out in a high-pressure reactor, and the reaction pressure is 6 MPa - 12 MPa. Preferably, the reaction in step 2) is carried out in a high-pressure reactor, and the reaction pressure is 10 MPa.

[0021] The reaction temperature in step 2) is 80 °C - 130 °C. Preferably, the reaction temperature in step 2) is 85 °C to 125 °C. More preferably, the reaction temperature in step 2) is 120 °C.

[0022] The reaction solvent in step 2) is selected from a mixed solution of methanol and water, a mixed solution of ethanol and water, a mixed solution of ethanol and tetrahydrofuran, a mixed solution of methanol and tetrahydrofuran, a mixed solution of isopropanol and tetrahydrofuran, a mixed solution of methanol and 1,4-dioxane, and a mixed solution of isopropanol and 1,4-dioxane. Preferably, the reaction solvent in step 2) is selected from a mixed solution of methanol and water.

[0023] The mass ratio of the catalyst to compound 2 in step 2) is 1:100 to 20:100. Preferably, the mass ratio of the catalyst to compound 2 is 1:100 to 10:100. More preferably, the mass ratio of the catalyst to compound 2 is 1:100, 2:100, 3:100, 5:100.

[0024] The reaction time in step 2) is 1 h to 48 h. Preferably, the reaction time in step 2) is 5 h to 36 h. More preferably, the reaction time in step 2) is 24 h.

[0025] The post-treatment may further be included in step 2): removing the catalyst, concentrating under reduced pressure to obtain S-hydroxypropyltetrahydropyran-3-ol.

[0026] In some embodiments, a method for preparing hydroxypropylpyran-3-ol includes: adding D-xylose (compound 1) and acetylacetone to a solvent, reacting at 5 °C - 25 °C, and after the reaction is complete, through extraction and concentration, acetonyltetrahydropyran-3-ol (compound 2) is obtained; then in the presence of a catalyst 10% nickel on carbon in a high-pressure reactor, hydrogen is introduced, the pressure is controlled at 6 MPa - 12 MPa, and the temperature is between 80 °C - 130 °C to carry out the carbonyl reduction reaction. After the reaction is complete, through filtration and concentration, hydroxypropylpyran-3-ol is obtained.

[0027] In some embodiments, a method for preparing propylpyranetriol includes: adding D-xylose (Compound 1) and acetylacetone into water, reacting at 5°C - 10°C for 2 hours, then raising the temperature to 25°C for reaction. After the reaction is complete, it is extracted with dichloromethane and concentrated to obtain acetonyltetrahydropyranetriol (Compound 2); then in the presence of 10% nickel-carbon catalyst, a mixed solvent of methanol and water is added, and it is reacted with Compound 2 in a high-pressure reactor. Hydrogen is introduced, and the pressure is controlled between 10 MPa and the temperature is between 120°C for carbonyl reduction reaction. After the reaction is complete, it is filtered and concentrated to obtain propylpyranetriol.

[0028] Compared with the prior art, the present invention includes the following beneficial technical effects:

[0029] The innovation point of the technical solution of the present invention is to replace the expensive ruthenium-carbon catalyst with an inexpensive catalyst, significantly reducing the cost. At the same time, the prepared boswellin product has an S configuration:R configuration = 50:50 - 55:45, meeting the market's expectation for enhancing the physiological activity of boswellin.

[0030] In the description of this specification, the descriptions referring to terms such as "one embodiment", "some embodiments", "example", "specific example", or "some examples" mean that the specific features, structures, materials, or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described can be combined in a suitable manner in any one or more embodiments or examples. In addition, without contradiction, those skilled in the art can combine and combine the different embodiments or examples described in this specification and the features of different embodiments or examples.

[0031] In the present invention, the expressions such as "Compound 1" and "the compound shown in Formula 1" and "Formula 1" represent the same compound.

[0032] In the present invention, "optionally" means that it can be carried out or not carried out. For example, optional post-treatment means that post-treatment can be carried out or not carried out. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 It is the HPLC chromatogram using ruthenium-carbon in Example 5;

[0034] Figure 2 It is the HPLC chromatogram using nickel-carbon in Example 5. DETAILED DESCRIPTION OF THE INVENTION

[0035] To enable those skilled in the art to better understand the technical solution of the present invention, some non-limiting embodiments are further disclosed below to provide a more detailed description of the present invention.

[0036] All the reagents used in the present invention can be purchased from the market or prepared by the methods described in the present invention.

[0037] In the present invention, min represents minute; h represents hour; g represents gram; ml represents milliliter.

[0038] In the present invention, HPLC represents high performance liquid chromatography.

[0039] In the present invention, complete reaction means that the remaining reaction raw materials are less than 5%.

[0040] Example 1

[0041]

[0042] Add 30 g of D-xylose and 38 g of acetylacetone to 180 ml of water, cool down to 5°C, dropwise add 12 g of 30% sodium hydroxide aqueous solution. After the addition is completed, react at 5°C - 10°C for 2 hours, then raise the temperature to 25°C and react for 4 hours. Take a sample for in-process control to ensure complete reaction. Add 200 mL of dichloromethane, extract and separate the layers, collect the aqueous phase, add 150 mL of dichloromethane again for extraction and separation, collect the aqueous phase, and concentrate. The obtained residue is directly used for the next step.

[0043] Example 2

[0044]

[0045] In a stainless steel high-pressure reactor, add 100 mL of methanol and 80 mL of water, then add the product obtained in step 1, and then add 0.5 g of 10% nickel-carbon catalyst. Pass hydrogen to 10 MPa, heat to 120°C, react for 24 hours, cool down to room temperature, take a sample for in-process control to ensure complete reaction, filter to remove the catalyst, and concentrate the filtrate under reduced pressure to obtain the target product propyltetrahydropyrantriol, 30.5 g, with a yield of 79.4%. After detection by HPLC, the ratio of S configuration:R configuration = 51.75:48.25.

[0046] Example 3

[0047] According to the method in Example 2, while keeping other conditions unchanged, investigate the effects of changing the reaction solvent, the pressure in the reaction kettle, and the catalyst on the purity and yield of propyltetrahydropyrantriol in the second-step reaction.

[0048] Table 1 Effects of solvent, pressure, and catalyst on the S configuration:R configuration and yield of propyltetrahydropyrantriol

[0049]

[0050]

[0051] As can be seen from Table 1, after screening, we selected 10% nickel-carbon as the catalyst, and the ratio of the S configuration to the R configuration of the product was 51.75:48.25, and the yield could reach 79.4%.

[0052] Example 4

[0053] According to the method in Example 2, with the catalyst fixed as 10% nickel-carbon, the pressure as 10 MPa, the reaction solvent as methanol-water, and other conditions unchanged, the effects of the reaction temperature, reaction time, and molar ratio of the catalyst to Compound 2 in Step 2 on the S configuration:R configuration and yield of propyltetrahydropyranyl triol were investigated.

[0054] Table 2 Effects of changing process parameters on the S configuration:R configuration and yield of propyltetrahydropyranyl triol

[0055]

[0056] As can be seen from Table 2, after screening, when the mass ratio of the catalyst to Compound 2 is between 1:100 and 10:100, the reaction time is between 12 - 24, and the reaction temperature is between 120°C and 130°C, it is beneficial to the progress of the reaction.

[0057] Example 5

[0058] According to the method in Example 2, with the pressure fixed at 10 MPa, the reaction solvent as methanol-water, and the reaction temperature at 120°C, and other conditions unchanged, the effects of the catalyst in Step 2 on the S configuration:R configuration and yield of propyltetrahydropyranyl triol were investigated.

[0059] Table 3 Effects of changing the catalyst on the S configuration:R configuration and yield of propyltetrahydropyranyl triol

[0060]

[0061] It can be seen from Table 3 that for the reaction involving the ruthenium-carbon catalyst, the ratio of the S configuration to the R configuration of propyltetrahydropyranyl triol can only reach 46 - 47:54 - 53, while for the reaction catalyzed by the nickel-carbon catalyst, the ratio of the S configuration to the R configuration of propyltetrahydropyranyl triol can reach 50 - 55:50 - 45; the obtained product has better efficacy, and the market prefers the latter. Therefore, it is more powerful to use nickel-carbon catalysis in the present invention and is more favored by the market.

[0062] Comparative Example 1

[0063] In a stainless steel high-pressure reactor, the compound 2 prepared according to the method in Example 1 was added to a mixed solvent of ethanol and water. 1.5 g of 10% nickel-carbon was added, hydrogen was introduced to 10 MPa, and the mixture was stirred and reacted for 12 hours. Then, it was filtered and concentrated to obtain 30.2 g of propyltetrahydropyranyl triol with a yield of 78.6%. By liquid-phase detection, the ratio of S configuration to R configuration was 52.3%:47.7%.

[0064] Comparative Example 2

[0065] In a stainless steel high-pressure reactor, the compound 2 prepared according to the method in Example 1 was added to water. 1.5 g of 10% ruthenium-carbon was added, hydrogen was introduced to 10 MPa, and the mixture was stirred and reacted for 12 hours. Then, it was filtered and concentrated to obtain 27.1 g of propyltetrahydropyranyl triol with a yield of 70.7%. By liquid-phase detection, the ratio of S configuration to R configuration was 47.2%:52.8%.

[0066] By comparing Example 1 and Example 2, it can be concluded that when preparing the same amount of product, the consumption of nickel-carbon is 89.8% of that of ruthenium-carbon. Since the market price of nickel-carbon is 10% of that of ruthenium-carbon, the cost of using nickel-carbon is only 8.98% of that of ruthenium-carbon, resulting in a significant cost reduction.

[0067] The method of the present invention has been described through preferred embodiments. It is obvious that relevant personnel can make changes, appropriate modifications and combinations to the methods and applications described herein within the content, spirit and scope of the present invention to implement and apply the technology of the present invention. Those skilled in the art can draw on the content of this article and appropriately modify the process parameters to achieve it. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are all considered to be included in the present invention.

Claims

1. A method for preparing propyltetrahydropyranyl triol, characterized in that, It includes the following steps: 1) D-xylose reacts with acetylacetone in a solvent to obtain acetonyltetrahydropyran triol; 2) In the presence of a catalyst and a solvent, acetonyltetrahydropyran triol undergoes a carbonyl reduction reaction with hydrogen to obtain hydroxypropyltetrahydropyran triol; Among them, the structural formula of acetonyltetrahydropyran triol is as follows: Among them, in step 1), a base is added for the reaction, and the base is selected from at least one of sodium hydroxide, potassium hydroxide, sodium bicarbonate, and sodium carbonate; In step 2), the catalyst is a nickel-carbon catalyst; the reaction pressure in step 2) is 6 MPa - 12 MPa; the reaction temperature in step 2) is 80 °C - 130 °C; In step 2), the reaction solvent is selected from one of a mixed solution of methanol and water, a mixed solution of ethanol and water, a mixed solution of ethanol and tetrahydrofuran, a mixed solution of methanol and tetrahydrofuran, and a mixed solution of methanol and 1,4-dioxane.

2. The method according to claim 1, wherein In step 1), the reaction solvent is selected from one of methanol, water, ethanol, tetrahydrofuran, isopropanol, and 1,4-dioxane.

3. The method according to claim 1, characterized in that In step 1), the molar ratio of acetylacetone to D-xylose is 1:1 to 3:

1.

4. The method according to claim 1, wherein The reaction time in step 1) is 30 min to 10 h.

5. The method according to claim 1, characterized in that, In step 2), the mass ratio of the catalyst to acetonyltetrahydropyran triol is 1:100 to 20:

100.

6. The method according to claim 1, wherein The reaction time in step 2) is 1 h to 48 h.

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