A high-purity S-configuration boson and its preparation method

Abstract

This invention discloses a continuous preparation and purification method for high-purity S-configuration Bosein. The method includes the following steps: A mixed aqueous solution of D-xylose, alkali, and acetylacetone is introduced into a microchannel continuous apparatus. The reaction temperature and flow rate are controlled to obtain the reaction intermediate 1-C-(β-D-xylanopyranosyl)-acetone. Then, 1-C-(β-D-xylanopyranosyl)-acetone, a chiral Ir catalyst, sodium acetate, and hydrogen are introduced into the microchannel continuous apparatus at a controlled flow rate. The reaction temperature, pressure, and residence time are controlled to continuously reduce the acetone with hydrogen. After desalting, decolorization, and recrystallization, high-purity S-configuration Bosein is obtained. The 1H NMR spectrum shows an S:R configuration ratio of 100:0, with 100% S-configuration Bosein and 0% R-configuration Bosein. HPLC analysis shows a purity greater than 99%. This continuous flow preparation method is high-purity, green, safe, and efficient, and has good market application prospects.

Description

Technical Field

[0001] This invention belongs to the field of cosmetics technology, specifically relating to a high-purity S-configuration bosine and its preparation method. Background Technology

[0002] Pro-Xylane (hydroxypropyl tetrahydropyrantriol) is an important cosmetic ingredient with a wide range of biological activities. Studies have shown that Pro-Xylane can directly affect the extracellular matrix in the three layers of the skin, promoting the production of hyaluronic acid and collagen, and indirectly increasing dermal collagen production, thereby promoting dermal repair, improving skin elasticity, and increasing skin firmness. Pro-Xylane is rich in natural antioxidants, which help maintain dermal elasticity, slow down the skin aging process, and protect the skin from damage caused by environmental pollution and ultraviolet radiation.

[0003] Studies have shown that among the two diastereomers of hydroxypropyltetrahydropyranotriol, the S-configuration is significantly more active than the R-configuration. This implies that the S-configuration of hydroxypropyltetrahydropyranotriol, as a more effective component of Bosein (CN116947795A), has broader application prospects. Due to its unique structural properties, industrial production often struggles to obtain a pure product in the S-configuration, typically resulting in a mixture of R / S configurations. Existing patent CN116947795A employs a discontinuous production process to obtain a pure product in the S-configuration, increasing the difficulty and cost of post-processing. Patent CN116425709A utilizes a batch reaction to obtain a pure S-configuration product, resulting in more impurities and a darker product color, and the use of large amounts of acid and sodium triacetoxyborohydride reducing agent further complicates and increases the cost of subsequent purification.

[0004] Due to current technological challenges, there is an urgent need to develop a high-purity, environmentally friendly, safe, efficient, and continuous method for producing S-hydroxypropyltetrahydropyrantriol to meet market demand for S-configuration Bosein. This method should be suitable for large-scale industrial production and yield high-quality products. Summary of the Invention

[0005] The purpose of this section is to outline some aspects of embodiments of the present invention and to briefly describe some preferred embodiments. Simplifications or omissions may be made in this section, as well as in the abstract and title of this application, to avoid obscuring the purpose of these documents; however, such simplifications or omissions should not be construed as limiting the scope of the invention.

[0006] In view of the problems existing in the above and / or prior art, the present invention is proposed.

[0007] Therefore, the purpose of this invention is to overcome the shortcomings of the prior art and provide a method for preparing high-purity S-configuration Bosein.

[0008] To solve the above-mentioned technical problems, the present invention provides the following technical solution: a method for preparing high-purity S-configuration Bosein, characterized in that it includes,

[0009] A mixed aqueous solution of D-xylose, alkali, and acetylacetone was introduced into a microchannel continuous reaction device at a controlled flow rate. The reaction temperature and residence time were controlled to continuously react and obtain the intermediate 1-C-(β-D-pyranoxysyl)-acetone reaction solution, which then flowed into a buffer tank.

[0010] Adjust the pH of the reaction solution to 7, add a chiral Ir catalyst and sodium acetate, and set the temperature to room temperature to obtain the intermediate solution;

[0011] The intermediate liquid and hydrogen are introduced into a microchannel continuous device by controlling the flow rate. The reaction temperature, pressure and residence time are controlled to continuously add hydrogen for reduction, and a hydrogenated reaction solution is obtained.

[0012] The hydrogenation reaction solution was decolorized, desalted, purified, and recrystallized to obtain high-purity S-configuration Bosein;

[0013] The chiral Ir catalyst has an S-configuration and the structure is as follows:

[0014]

[0015] In a preferred embodiment of the preparation method described in this invention, the flow rate of the mixed aqueous solution of D-xylose, alkali and acetylacetone is controlled and introduced into the microchannel continuous device, wherein the flow rate is 5 ml / min to 20 ml / min and the molar ratio of D-xylose, alkali and acetylacetone is 1:1 to 2:1 to 2.

[0016] In a preferred embodiment of the preparation method described in this invention, the alkali is at least one of sodium carbonate, sodium bicarbonate, and sodium hydroxide.

[0017] In a preferred embodiment of the preparation method described in this invention, the concentration of the D-xylose aqueous solution is 10-20%.

[0018] In a preferred embodiment of the preparation method described in this invention, the reaction temperature of the mixed aqueous solution of D-xylose, alkali and acetylacetone is 50-80°C, and the residence time is 30-50 min.

[0019] In a preferred embodiment of the preparation method described in this invention, the molar ratio of the chiral Ir catalyst to 1-C-(β-D-xylanosyl)-acetone is 1:100 to 1:200.

[0020] In a preferred embodiment of the preparation method described in this invention, the molar ratio of the chiral Ir catalyst to sodium acetate is 1:2 to 1:10.

[0021] In a preferred embodiment of the preparation method described in this invention, the intermediate liquid and hydrogen are introduced into the microchannel continuous device at a controlled flow rate of 15 ml / min to 20 ml / min.

[0022] In a preferred embodiment of the preparation method described in this invention, the reaction temperature of the intermediate liquid and hydrogen is 100-120°C, the reaction pressure is 2-3 MPa, and the reaction residence time is 20-40 min.

[0023] In a preferred embodiment of the preparation method described in this invention, the molar ratio of hydrogen to 1-C-(β-D-xylanosyl)-acetone is 5:1 to 10:1.

[0024] Beneficial effects of the present invention:

[0025] (1) In existing technologies, the use of batch and fixed-bed reactions results in intermediates with darker colors and more impurities, increasing the difficulty of subsequent purification. This invention adopts a continuous synthesis method, resulting in fewer byproducts and lighter-colored intermediates, simpler post-processing, and a white final product. The final product has a purity greater than 99% and can be directly used for industrial production of high-purity S-configuration Bosein.

[0026] (2) Existing technologies use a large amount of sodium triacetoxyborohydride reducing agent, which introduces a large amount of boric acid byproducts, making product separation and purification very difficult and increasing post-processing costs. This invention uses a continuous flow catalytic hydrogenation reaction method, which simplifies post-processing, avoids the introduction of boric acid, and reduces post-processing costs. The continuous synthesis of this invention can realize automated production, reducing time and labor costs and greatly improving production capacity.

[0027] (3) Traditional batch reactors cannot meet the requirements of green and safe production. This invention adopts a continuous production process. The reaction is completed in a continuous flow microchannel reactor. The total volume of the reaction fluid channel is small, which improves the safety of the reaction. At the same time, the solvent for the continuous reaction process is water, which makes the reaction greener and realizes safe and green production. Attached Figure Description

[0028] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. Wherein:

[0029] Figure 1 This is a schematic diagram of the structure of the microreactor of the present invention.

[0030] Figure 2The image shows the HPLC chromatogram of the sample from Example 1.

[0031] Figure 3 The image shows the NMR spectrum of the sample from Example 1.

[0032] Figure 4 This is a high-resolution mass spectrum of the sample from Example 1. Detailed Implementation

[0033] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the examples in the specification.

[0034] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0035] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.

[0036] Unless otherwise specified, all chemical reagents used in the embodiments of this invention are commercially available analytical grade reagents.

[0037] The preparation process of the chiral Ir catalyst in this embodiment of the invention is as follows:

[0038]

[0039] Example 1

[0040] (1) Prepare a mixed aqueous solution by mixing D-xylose, sodium hydroxide and acetylacetone in a molar ratio of 1:1.2:1.2. The concentration of the D-xylose aqueous solution is 20% (mass percentage). The solution is introduced into a microchannel continuous device at a flow rate of 10 ml / min. The temperature is set to 80℃ and the residence time is 30 minutes. The effluent 1-C-(β-D-xylanosyl)-acetone enters the buffer tank.

[0041] (2) The buffer solution was adjusted to pH=7 with hydrochloric acid, and then chiral Ir catalyst (0.5 mol%) and sodium acetate (4 mol%) were added to the buffer. The mixture was thoroughly mixed and introduced into the microchannel continuous device at a flow rate of 15 ml / min. The molar ratio of hydrogen to 1-C-(β-D-xylanosyl)-acetone was controlled to be 8:1. The solution and hydrogen were mixed in the inlet micro-sieve micro-mixer. The system pressure was 2.5 MPa, the temperature was set to 110 °C, and the residence time was 35 minutes. The reaction solution was collected at the outlet of the microreactor. After collecting the reaction solution, it was extracted with ethyl acetate to remove impurities. The aqueous phase was decolorized with activated carbon, and then desalted by electrodialysis and impurities were removed by DM-301 resin. Finally, it was slurried with ethanol and methyl tert-butyl ether to obtain high-purity S-configuration Bosein. The 1H NMR spectrum showed that the S:R configuration ratio was 100:0, the S configuration Bosein was 100%, the R configuration Bosein was 0%, the yield was 91%, and the purity was 100% as determined by HPLC.

[0042] Single S-configuration Bosein NMR 1H spectrum: 1 H NMR(500MHz,D2O)δ3.91(dd,J=12.7,6.3Hz,1H),3.81(dd,J=11.3,5.4Hz,1H),3.46(td,J=9.9,5.5Hz,1H),3.27(t,J=9.1Hz,1H),3.2 1(dd,J=13.4,5.6Hz,1H),3.13(t,J=11.0Hz,1H),3.06(t,J=9.2Hz,1H),1.85–1.75(m,1H),1.60–1.48(m,1H),1.08(d,J=6.2Hz,3H).

[0043] Single S-configuration Bosein [M+Na] + Theoretical data for high-resolution mass spectrometry: 215.0895; Actual value: 215.0896.

[0044] Example 2

[0045] (1) Prepare a mixed aqueous solution by mixing D-xylose, sodium hydroxide and acetylacetone in a molar ratio of 1:1.5:1.5. The concentration of the D-xylose aqueous solution is 15% (mass percentage). The solution is introduced into a microchannel continuous device at a flow rate of 15 ml / min. The temperature is set to 60℃ and the residence time is 40 minutes. The effluent 1-C-(β-D-xylanosyl)-acetone enters the buffer tank.

[0046] (2) Adjust the pH of the buffer solution to 7 with hydrochloric acid, then add chiral Ir catalyst (1 mol%) and sodium acetate (5 mol%) to the buffer, mix thoroughly, and pass it into the microchannel continuous device at a flow rate of 20 ml / min. Control the molar ratio of hydrogen to 1-C-(β-D-xylanosyl)-acetone to be 5:1. Mix the solution and hydrogen in the inlet micro-sieve micro-mixer. The system pressure is 2 MPa, the temperature is set to 100 °C, and the residence time is 20 minutes. Collect the reaction solution at the outlet of the microreactor. After collecting the reaction solution, extract it with ethyl acetate to remove impurities. Decolorize the aqueous phase with activated carbon, then desalt it by electrodialysis and remove impurities by DM-301 resin. Finally, recrystallize it with water and ethanol to obtain high-purity S-configuration Bosein. The S:R configuration ratio is 100:0, the S-configuration Bosein is 100%, the R-configuration Bosein is 0%, the yield is 85%, and the purity is 99.42% as determined by HPLC.

[0047] Example 3

[0048] The difference between this embodiment and Example 1 is that the molar ratio of the chiral Ir catalyst and sodium acetate in step (2) is replaced with 1:2, while the remaining steps are the same as in Example 1, and Bosein is obtained.

[0049] Example 4

[0050] The difference between this embodiment and Example 1 is that the molar ratio of the chiral Ir catalyst and sodium acetate in step (2) is replaced with 1:10, while the rest of the steps are the same as in Example 1, and Bosein is obtained.

[0051] Comparative Example 1

[0052] The difference between this embodiment and Example 1 is that the molar ratio of the chiral Ir catalyst and sodium acetate in step (2) is replaced with 1:1, while the remaining steps are the same as in Example 1, and Bosein is obtained.

[0053] Comparative Example 2

[0054] The difference between this embodiment and Example 1 is that the molar ratio of the chiral Ir catalyst and sodium acetate in step (2) is replaced with 1:12, while the rest of the steps are the same as in Example 1, and Bosein is obtained.

[0055] The configurations, yields, and purities of the Bosein prepared in Examples 1-4 and Comparative Examples 1 and 2 are shown in Table 1.

[0056] Table 1

[0057] S:R configuration ratio Yield / % purity / % Example 1 100:0 91 100 Example 2 100:0 85 99.42 Example 3 99:1 88 99.12 Example 4 98:2 82 99.23 Comparative Example 1 95:5 71 98.16 Comparative Example 2 93:7 80 97.21

[0058] Example 5

[0059] The difference between this embodiment and embodiment 1 is that the flow rate in step (2) is replaced with 17 ml / min, while the rest of the steps are the same as in embodiment 1, and Bosein is obtained.

[0060] Example 6

[0061] The difference between this embodiment and embodiment 1 is that the flow rate in step (2) is replaced with 19 ml / min, while the rest of the steps are the same as in embodiment 1, and Bosein is obtained.

[0062] Comparative Example 3

[0063] The difference between this embodiment and embodiment 1 is that the flow rate in step (2) is replaced with 5 ml / min, while the rest of the steps are the same as in embodiment 1, and Bosein is obtained.

[0064] Comparative Example 4

[0065] The difference between this embodiment and embodiment 1 is that the flow rate in step (2) is replaced with 30 ml / min, while the rest of the steps are the same as in embodiment 1, and Bosein is obtained.

[0066] The configurations, yields, and purities of the Bosein prepared in Examples 1, 5, and 6 and Comparative Examples 3 and 4 are shown in Table 2.

[0067] Table 2

[0068]

[0069]

[0070] Example 7

[0071] The difference between this embodiment and Example 1 is that the molar ratio of hydrogen and 1-C-(β-D-xylanosyl)-acetone in step (2) is replaced with 6:1, while the remaining steps are the same as in Example 1, to obtain Bosein.

[0072] Example 8

[0073] The difference between this embodiment and Example 1 is that the molar ratio of hydrogen and 1-C-(β-D-xylanosyl)-acetone in step (2) is replaced with 9:1, and the remaining steps are the same as in Example 1, to obtain Bosein.

[0074] Comparative Example 5

[0075] The difference between this embodiment and Example 1 is that the molar ratio of hydrogen and 1-C-(β-D-xylanosyl)-acetone in step (2) is replaced with 1:1, while the remaining steps are the same as in Example 1, to obtain Bosein.

[0076] Comparative Example 6

[0077] The difference between this embodiment and Example 1 is that the molar ratio of hydrogen and 1-C-(β-D-xylanosyl)-acetone in step (2) is replaced with 11:1, and the remaining steps are the same as in Example 1, to obtain Bosein.

[0078] The configurations, yields, and purities of the bosonicines obtained in Examples 1, 7, and 8 and Comparative Examples 5 and 6 are shown in Table 3.

[0079] Table 3

[0080] S:R configuration ratio Yield / % purity / % Example 1 100:0 91 100 Example 7 100:0 87 99.35 Example 8 100:0 83 99.45 Comparative Example 5 99:1 72 98.66 Comparative Example 6 97:3 84 98.74

[0081] Comparative Example 7

[0082] The difference between this embodiment and embodiment 1 is that sodium acetate in step (2) is replaced with sodium carbonate, while the remaining steps are the same as in embodiment 1, and Bosein is obtained.

[0083] The configuration, yield, and purity of the bosonic acid obtained in Example 1 and Comparative Example 7 are shown in Table 4.

[0084] Table 4

[0085]

[0086]

[0087] This invention utilizes a chiral Ir catalyst, sodium acetate, and hydrogen gas introduced into a microchannel continuous reactor. By controlling the reaction temperature, pressure, and residence time, a continuous-flow catalytic hydrogenation reaction is employed. This simplifies post-processing, avoids the introduction of boric acid, and reduces post-processing costs. The continuous synthesis of this invention enables automated production, reducing time and labor costs and significantly increasing production capacity. The continuous-flow preparation method of this invention offers high purity, is environmentally friendly, safe, and efficient, and has promising market application prospects.

[0088] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the present invention.

Claims

1. A method for preparing high-purity S-configuration Bosein, characterized in that: include, A mixed aqueous solution of D-xylose, alkali, and acetylacetone was introduced into a microchannel continuous reaction device at a controlled flow rate. The reaction temperature and residence time were controlled to continuously react and obtain the intermediate 1-C-(β-D-pyranoxysyl)-acetone reaction solution, which then flowed into a buffer tank. Adjust the pH of the reaction solution to 7, add a chiral Ir catalyst and sodium acetate, and set the temperature to room temperature to obtain the intermediate solution; The intermediate liquid and hydrogen are introduced into a microchannel continuous device by controlling the flow rate. The reaction temperature, pressure and residence time are controlled to continuously add hydrogen for reduction, and a hydrogenated reaction solution is obtained. The hydrogenation reaction solution was decolorized, desalted, purified, and recrystallized to obtain high-purity S-configuration Bosein; The chiral Ir catalyst has an S-configuration and the structure is as follows:

2. The preparation method according to claim 1, characterized in that: The controlled flow rate involves introducing a mixed aqueous solution of D-xylose, alkali, and acetylacetone into a microchannel continuous device, wherein the flow rate is 5 ml / min to 20 ml / min, and the molar ratio of D-xylose, alkali, and acetylacetone is 1:1 to 2:1 to 2.

3. The preparation method according to claim 2, characterized in that: The alkali is at least one of sodium carbonate, sodium bicarbonate, and sodium hydroxide.

4. The preparation method according to claim 1, characterized in that: The concentration of the D-xylose aqueous solution is 10-20%.

5. The preparation method according to claim 1, characterized in that: The reaction temperature of the mixed aqueous solution of D-xylose, alkali and acetylacetone is 50-80℃, and the residence time is 30-50 min.

6. The preparation method according to claim 1, characterized in that: The molar ratio of the chiral Ir catalyst to 1-C-(β-D-xylanosyl)-acetone is 1:100 to 1:

200.

7. The preparation method according to claim 1, characterized in that: The molar ratio of the chiral Ir catalyst to sodium acetate is 1:2 to 1:

10.

8. The preparation method according to claim 1, characterized in that: The controlled flow rate is used to introduce the intermediate liquid and hydrogen into the microchannel continuous device, wherein the flow rate is 15 ml / min to 20 ml / min.

9. The preparation method according to claim 1, characterized in that: The reaction temperature of the intermediate liquid and hydrogen is 100-120℃, the reaction pressure is 2-3MPa, and the reaction residence time is 20-40min.

10. The preparation method according to claim 1, characterized in that: The molar ratio of hydrogen to 1-C-(β-D-xylanosyl)-acetone is 5:1 to 10:1.

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