High-purity S-configuration boine and preparation method thereof

Abstract

The invention discloses a continuous preparation and purification method of high-purity S-configuration glassine, and the method comprises the following steps: introducing a mixed aqueous solution of D-xylose, alkali and acetylacetone into a micro-channel continuous device, controlling the reaction temperature and flow velocity to obtain a reaction intermediate 1-C-(beta-D-xylopyranyl)-acetone, and carrying out continuous preparation and purification on the reaction intermediate 1-C-(beta-D-xylopyranyl)-acetone to obtain the high-purity S-configuration glassine. 1-C-(beta-D-xylopyranosyl)-acetone, a chiral Ir catalyst, sodium acetate and hydrogen are introduced into a micro-channel continuous device by controlling the flow rate, the reaction temperature, pressure and retention time are controlled, continuous hydrogenation reduction is carried out, high-purity S-configuration glassine is obtained through desalination, decoloration and recrystallization, a nuclear magnetic hydrogen spectrum shows that the S-to-R configuration ratio is 100: 0, the S-configuration glassine is 100%, and the purity of the S-configuration glassine is 100%. The R-configuration glass color is 0%, and the HPLC detection purity is greater than 99%. The continuous flow preparation method disclosed by the invention is high in purity, green, safe and efficient, and has a good market application prospect.

Description

Technical Field

[0001] The invention belongs to the technical field of cosmetics, and specifically relates to a high-purity S-configuration bosonine and a preparation method thereof. Background Art

[0002] Bosera (hydroxypropyl tetrahydropyrantriol) is an important cosmetic raw material with a wide range of biological activities. Studies have shown that bosera can directly affect the extracellular matrix in the three-layer structure of the skin, promote the production of hyaluronic acid and collagen, and indirectly increase the production of dermal collagen, thereby promoting dermal repair, improving skin elasticity and increasing skin firmness; bosera is rich in natural antioxidants, which help maintain the elasticity of the dermis, slow down the skin aging process, and protect the skin from damage such as environmental pollution and ultraviolet radiation.

[0003] Studies have shown that among the two diastereoisomers of hydroxypropyl tetrahydropyrantriol, the activity of the S-configuration is significantly higher than that of the R-configuration. This means that the S-configuration of hydroxypropyl tetrahydropyrantriol, as a more effective bosine component (CN116947795A), has a wider application prospect. Due to its special structural properties, it is often difficult to obtain a single S-configuration pure product in industrial production, which is usually a mixture of R / S configurations. The existing patent CN116947795A adopts discontinuous production of a single S-configuration pure product, which increases the difficulty and cost of post-processing; the patent CN116425709A uses a kettle reaction to obtain an S-configuration pure product, which will cause more impurities and a darker product color, and uses a large amount of acid and sodium triacetoxyborohydride reducing agent, which increases the difficulty and cost of subsequent processing and purification.

[0004] Due to the challenges of current technology, it is urgent to develop a method for producing S-hydroxypropyl tetrahydropyrantriol with high purity, green safety, high efficiency and continuous production to meet the market demand for S-configuration bosine. This method should be suitable for large-scale industrial production and the resulting product should be of high quality. Summary of the invention

[0005] The purpose of this section is to summarize some aspects of embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the specification abstract and the invention title of this application to avoid blurring the purpose of this section, the specification abstract and the invention title, and such simplifications or omissions cannot be used to limit the scope of the present invention.

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

[0007] Therefore, the purpose of the present invention is to overcome the deficiencies in the prior art and provide a method for preparing high-purity S-configuration boson.

[0008] In order to solve the above technical problems, the present invention provides the following technical solution: a method for preparing high-purity S-configuration boson, characterized in that: comprising:

[0009] Control the flow rate to pass the mixed aqueous solution of D-xylose, alkali and acetylacetone into the microchannel continuous device, control the reaction temperature and residence time, and continuously react to obtain the intermediate 1-C-(β-D-pyranose xyloyl)-acetone reaction liquid, which flows into the buffer tank;

[0010] The pH of the reaction solution was adjusted to 7, a chiral Ir catalyst and sodium acetate were added, and the temperature was set to room temperature to obtain an intermediate liquid;

[0011] Control the flow rate to pass the intermediate liquid and hydrogen into the microchannel continuous device, control the reaction temperature, pressure and residence time, and continuously perform hydrogenation reduction to obtain a hydrogenation reaction liquid;

[0012] The hydrogenation reaction liquid is decolorized, desalted, impurized, and recrystallized to obtain high-purity S-configuration Bose-like substance;

[0013] The chiral Ir catalyst is in S-configuration and has the following structure:

[0014]

[0015] As a preferred embodiment of the preparation method of the present invention, the mixed aqueous solution of D-xylose, alkali and acetylacetone is passed into the microchannel continuous device by controlling the flow rate, 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] As a preferred embodiment of the preparation method of the present invention, the base is at least one of sodium carbonate, sodium bicarbonate and sodium hydroxide.

[0017] As a preferred embodiment of the preparation method of the present invention, the concentration of the D-xylose aqueous solution is 10-20%.

[0018] As a preferred embodiment of the preparation method of the present 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] As a preferred embodiment of the preparation method of the present invention, the molar ratio of the chiral Ir catalyst to 1-C-(β-D-xylopyranosyl)-acetone is 1:100 to 1:200.

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

[0021] As a preferred embodiment of the preparation method of the present 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] As a preferred embodiment of the preparation method of the present 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] As a preferred embodiment of the preparation method of the present invention, the molar ratio of hydrogen to 1-C-(β-D-xylopyranosyl)-acetone is 5:1 to 10:1.

[0024] Beneficial effects of the present invention:

[0025] (1) In the prior art process, the use of kettle and fixed bed reactions will result in darker intermediate colors and more impurities, which will increase the difficulty of subsequent treatment and purification. The present invention adopts a continuous synthesis method, which has fewer by-products and lighter intermediate colors, simple post-treatment, and the final product is white. The purity of the final product is greater than 99%, and high-purity S-configuration boson can be directly produced industrially.

[0026] (2) The prior art uses a large amount of sodium triacetoxyborohydride reducing agent, which will introduce a large amount of boric acid byproducts, making the separation and purification of the product very difficult and increasing the cost of post-processing. The present invention adopts a continuous flow catalytic hydrogenation reaction mode, which is simple to post-process, avoids the introduction of boric acid, and reduces the cost of post-processing. The continuous synthesis of the present invention can realize automated production, reduce time and labor costs, and greatly improve production capacity.

[0027] (3) Traditional kettle reactions cannot meet the requirements of green and safe production. The present invention adopts full-process continuous production. 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 full-process continuous reaction is water, which makes the reaction greener and realizes safe and green production. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative labor. Among them:

[0029] Figure 1 Schematic diagram of the structure of the microreactor of the present invention.

[0030] Figure 2This is the HPLC detection spectrum of the sample in Example 1.

[0031] Figure 3 This is the NMR detection spectrum of the sample in Example 1.

[0032] Figure 4 This is the high-resolution mass spectrum of the sample in Example 1. DETAILED DESCRIPTION

[0033] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0034] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein, and those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present 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 term "in one embodiment" that appears in different places in this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive with other embodiments.

[0036] Unless otherwise specified, the chemical reagents used in the examples of the present invention are all commercially available analytically pure.

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

[0038]

[0039] Example 1

[0040] (1) D-xylose, sodium hydroxide and acetylacetone were prepared into a mixed aqueous solution with a molar ratio of 1:1.2:1.2. The concentration of the D-xylose aqueous solution was 20% (mass percentage). The solution was introduced into a microchannel continuous device at a flow rate of 10 ml / min. The temperature was set to 80°C. The residence time was 30 minutes. The effluent 1-C-(β-D-pyranosyl)-acetone entered a buffer tank.

[0041] (2) The buffer tank 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 tank, mixed thoroughly, 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-xylopyranosyl)-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, and the reaction solution 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 Bose-ene. The nuclear magnetic hydrogen spectrum showed that the S:R configuration ratio was 100:0, the S-configuration Bose-ene was 100%, the R-configuration Bose-ene was 0%, the yield was 91%, and the purity detected by HPLC was 100%.

[0042] Single S-configuration Bose-NMR H 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 Bose [M+Na] + High-resolution mass spectrometry theoretical data: 215.0895; actual value: 215.0896.

[0044] Example 2

[0045] (1) D-xylose, sodium hydroxide and acetylacetone were prepared into a mixed aqueous solution with a molar ratio of 1:1.5:1.5. The concentration of the D-xylose aqueous solution was 15% (mass percentage). The solution was introduced into a microchannel continuous device at a flow rate of 15 ml / min. The temperature was set to 60°C. The residence time was 40 minutes. The effluent 1-C-(β-D-pyranosyl)-acetone entered a buffer tank.

[0046] (2) The buffer tank solution was adjusted to pH=7 with hydrochloric acid, and then chiral Ir catalyst (1 mol%) and sodium acetate (5 mol%) were added to the buffer tank, mixed thoroughly, and introduced into the microchannel continuous device at a flow rate of 20 ml / min, and the molar ratio of hydrogen to 1-C-(β-D-xylopyranosyl)-acetone was controlled to be 5:1. The solution and hydrogen were mixed in the inlet micro-sieve micro-mixer. The system pressure was 2 MPa, the temperature was set to 100°C, and the residence time was 20 minutes. The reaction liquid was collected at the outlet of the microreactor, and the reaction liquid 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 recrystallized by water and ethanol to obtain high-purity S-configuration Bose-ene, the S:R configuration ratio was 100:0, the S-configuration Bose-ene was 100%, the R-configuration Bose-ene was 0%, the yield was 85%, and the purity detected by HPLC was 99.42%.

[0047] Example 3

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

[0049] Example 4

[0050] The difference between this embodiment and embodiment 1 is that the molar ratio of the chiral Ir catalyst and sodium acetate in step (2) is replaced with 1:10, and the remaining steps are the same as those in embodiment 1 to obtain bosonine.

[0051] Comparative Example 1

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

[0053] Comparative Example 2

[0054] The difference between this embodiment and embodiment 1 is that the molar ratio of the chiral Ir catalyst and sodium acetate in step (2) is replaced with 1:12, and the remaining steps are the same as those in embodiment 1 to obtain bosonine.

[0055] The configuration, yield and purity of the boson prepared in Examples 1 to 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, and the remaining steps are the same as those in embodiment 1 to obtain boson.

[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, and the remaining steps are the same as those in embodiment 1 to obtain boson.

[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, and the remaining steps are the same as those in embodiment 1 to obtain boson.

[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, and the remaining steps are the same as those in embodiment 1 to obtain boson.

[0066] The configuration, yield and purity of the boson prepared in Examples 1, 5, 6 and Comparative Examples 3, 4 are shown in Table 2.

[0067] Table 2

[0068]

[0069]

[0070] Example 7

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

[0072] Example 8

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

[0074] Comparative Example 5

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

[0076] Comparative Example 6

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

[0078] The configuration, yield and purity of the boson prepared in Examples 1, 7, 8 and Comparative Examples 5, 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 the sodium acetate in step (2) is replaced by sodium carbonate, and the remaining steps are the same as those in embodiment 1 to obtain bosonine.

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

[0084] Table 4

[0085]

[0086]

[0087] The present invention uses a chiral Ir catalyst, sodium acetate and hydrogen to pass into a microchannel continuous device, controls the reaction temperature, pressure and residence time, adopts a continuous flow catalytic hydrogenation reaction mode, and has simple post-processing, avoids the introduction of boric acid, reduces post-processing costs, and the continuous synthesis of the present invention can realize automated production, reduces time and labor costs, and greatly improves production capacity. The continuous flow preparation method of the present invention is high in purity, green, safe, and efficient, and has good market application prospects.

[0088] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention can be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the present invention.

Claims

1. A method for preparing high-purity S-configuration boson, characterized in that: include, Control the flow rate to pass the mixed aqueous solution of D-xylose, alkali and acetylacetone into the microchannel continuous device, control the reaction temperature and residence time, and continuously react to obtain the intermediate 1-C-(β-D-pyranose xyloyl)-acetone reaction liquid, which flows into the buffer tank; The pH of the reaction solution was adjusted to 7, a chiral Ir catalyst and sodium acetate were added, and the temperature was set to room temperature to obtain an intermediate liquid; Control the flow rate to pass the intermediate liquid and hydrogen into the microchannel continuous device, control the reaction temperature, pressure and residence time, and continuously perform hydrogenation reduction to obtain a hydrogenation reaction liquid; The hydrogenation reaction liquid is decolorized, desalted, impurized, and recrystallized to obtain high-purity S-configuration Bose-like substance; The chiral Ir catalyst is in S-configuration and has the following structure:

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

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° C., 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-xylopyranosyl)-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 intermediate liquid and hydrogen are introduced into the microchannel continuous device by controlling the flow rate, 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° C., the reaction pressure is 2-3 MPa, and the reaction residence time is 20-40 min.

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

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