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CN-122012662-A - Process for green synthesis of high-purity stearyl glycyrrhetinate based on enzyme catalysis

CN122012662ACN 122012662 ACN122012662 ACN 122012662ACN-122012662-A

Abstract

The invention relates to the technical field of organic synthesis and biochemical engineering, in particular to a process for synthesizing high-purity stearyl glycyrrhetinate based on enzyme catalysis, which comprises the following steps of S1, dissolving glycyrrhizic acid or salt thereof in a buffer solution, adding immobilized beta-glucosidase, and carrying out reaction post-treatment to obtain a glycyrrhetinic acid intermediate; S2, adding the glycyrrhetinic acid intermediate, stearyl alcohol and a catalyst obtained in the step S1 into an organic solvent, reacting, purifying, and drying by supercritical CO 2 to obtain stearyl alcohol glycyrrhetinate. The invention prepares the high-purity stearyl glycyrrhetinate by using stable MOF as a framework, using functionalized ionic liquid as an interface layer and using a trinity structured composite catalyst with high-activity lipase as a catalytic core, and the synthesis process is environment-friendly, the reaction condition is mild, and the catalyst can be recycled.

Inventors

  • ZHU ZHIXIAN
  • ZHANG JIARONG
  • Huo Cunlu
  • ZHU XIANGQIAN
  • GAO LI
  • GAO YING
  • ZHAO FUHU

Assignees

  • 甘肃泛植制药有限公司

Dates

Publication Date
20260512
Application Date
20260211

Claims (10)

  1. 1. A process for green synthesis of high-purity stearyl glycyrrhetinate based on enzyme catalysis, which is characterized by comprising the following steps: s1, dissolving glycyrrhizic acid or salt thereof in a buffer solution, adding immobilized beta-glucosidase, reacting for 4-6 hours at 40-60 ℃ and 180-250rpm, and performing post-treatment to obtain a glycyrrhizic acid intermediate; S2, adding the glycyrrhetinic acid intermediate, stearyl alcohol and a catalyst obtained in the step S1 into an organic solvent, reacting for 17-20 hours at 50-70 ℃, purifying, and drying by supercritical CO 2 to obtain stearyl alcohol glycyrrhetinate.
  2. 2. The enzyme-catalyzed green synthesis process of high purity stearyl glycyrrhetinate according to claim 1, wherein the buffer solution in step S1 is 0.05-0.2mol/L acetic acid-sodium acetate buffer or citric acid-disodium hydrogen phosphate buffer.
  3. 3. The process for synthesizing high-purity stearyl glycyrrhetinate based on enzyme catalysis according to claim 1, wherein the addition amount of the immobilized beta-glucosidase in the step S1 is 1% -5% of the mass of glycyrrhizic acid or salt thereof.
  4. 4. The process for the green synthesis of high purity stearyl glycyrrhetinate based on enzymatic catalysis according to claim 1, characterized in that the preparation method of the catalyst comprises the following steps: (1) Adding 4-dimethylaminobenzoic acid and 1-hydroxyethyl-3-methylimidazole chloride into toluene, adding concentrated sulfuric acid while stirring, reacting at 70-80 ℃ for 5-6h, washing, and steaming to obtain a compound, adding potassium acetate and ethanol into the obtained compound, stirring at 40-60 ℃ for 36-48h, filtering, and steaming to obtain a product; (2) Adding zirconium tetrachloride, 2-amino terephthalic acid and acetic acid into DMF, performing ultrasonic dispersion, then reacting for 12-14h at 120-130 ℃, washing and drying to obtain UiO-66-NH 2 ; (3) Adding the product obtained in the step (1) and the UiO-66-NH 2 obtained in the step (2) into methanol, and stirring for 24-30h at 35-45 ℃ to obtain modified UiO-66-NH 2 ; (4) Adding lipase into phosphate buffer solution, performing ultrasonic dispersion, then adding the lipase into the modified UiO-66-NH 2 obtained in the step (3), stirring for 3-4h at 30-40 ℃, filtering, washing and drying to obtain the catalyst.
  5. 5. The process for the enzymatic green synthesis of high purity stearyl glycyrrhetinate according to claim 4, characterized in that the mass ratio of the product in step (3) to UiO-66-NH 2 is (0.1-0.3): 1.
  6. 6. The process for the enzyme-catalyzed green synthesis of high purity stearyl glycyrrhetinate according to claim 4, wherein the mass ratio of lipase to modified UiO-66-NH 2 in step (4) is (2-2.5): 1.
  7. 7. The process for synthesizing high-purity stearyl glycyrrhetinate based on enzyme catalysis in green according to claim 1, wherein the catalyst in step S2 is added in an amount of 10% -30% of the mass of the glycyrrhetinic acid intermediate.
  8. 8. The enzyme-catalyzed green synthesis process for high purity stearyl alcohol glycyrrhetinate according to claim 1, wherein the molar feed ratio of stearyl alcohol to glycyrrhetinic acid intermediate in step S2 is 1 (1-1.5).
  9. 9. The process for synthesizing high-purity stearyl glycyrrhetinate based on enzyme catalysis green according to claim 1, wherein the purification step in the step S2 is that after the catalyst is removed by filtration, the product is concentrated and dried under reduced pressure, and the dried product is dissolved in methanol or ethanol at 50-75 ℃ and stirred for 2-3 hours, and then subjected to programmed cooling crystallization.
  10. 10. The enzyme-catalyzed green process for synthesizing high purity stearyl glycyrrhetinate according to claim 1, wherein the purity of stearyl glycyrrhetinate is not less than 99.5%, APHA color number is less than 20, and solvent residue is less than 10 ppm.

Description

Process for green synthesis of high-purity stearyl glycyrrhetinate based on enzyme catalysis Technical Field The invention relates to the technical field of organic synthesis and biochemical engineering, in particular to a process for green synthesis of high-purity stearyl glycyrrhetinate based on enzyme catalysis. Background The skin care value of the active ingredient of the liquorice serving as the traditional medicinal plant is fully verified by modern science, wherein the glycyrrhetinic acid becomes one of the core directions of developing the effective cosmetic raw materials due to the obvious anti-inflammatory and soothing effects. However, natural glycyrrhetinic acid has the defects of poor fat solubility, low skin permeability, poor formula compatibility and the like, and limits the application efficacy of the natural glycyrrhetinic acid in main-stream cosmetic formulations such as cream, sun protection and the like. In order to solve the problem, chemical modification is adopted to optimize the physicochemical properties of the glycyrrhetinic acid, namely the glycyrrhetinic acid ester of stearyl alcohol is a derivative product obtained by esterification reaction of the glycyrrhetinic acid and stearyl alcohol, and the glycyrrhetinic acid ester of stearyl alcohol gradually becomes a preferable active ingredient in the field of cosmetics by virtue of performance improvement brought by introducing a lipophilic higher alkanol structure. The prior researches prove that the stearyl glycyrrhetinate has multiple skin care effects, has better anti-inflammatory activity than natural glycyrrhetinic acid, can reduce the expression of inflammatory factors such as IL-6, TNF-alpha and the like by inhibiting NF- κB signal paths, can competitively inhibit tyrosinase activity, and realizes the synergistic effects of relieving allergy resistance, whitening skin and removing spots. In addition, the composition has good ultraviolet absorption capability, can enhance the light protection effect of the sun-screening product, can promote the synthesis of skin silk fibroin and hyaluronic acid, repair the boosting barrier, keep moisture and maintain stability, is suitable for various skin care scenes with problems such as sensitive muscles and acne muscles, has continuous rising market application demands, and develops different processes for synthesizing stearyl glycyrrhetinate for meeting the market demands. Patent CN103833820A discloses a method for synthesizing 3-succinic acid-30-stearyl glycyrrhetinate. The method takes glycyrrhetinic acid as a starting material, nucleophilic substitution is carried out on the glycyrrhetinic acid and octadecyl bromide, and the glycyrrhetinic acid and succinic anhydride are condensed to obtain 3-succinic acid-30-stearyl glycyrrhetinate. The invention removes the reaction using condensing agent in the prior art by improving the intermediate synthesis method, reduces the generation of reaction waste, simplifies the process steps, greatly improves the reaction yield, and has the advantages of simple operation, suitability for industrial production, high product purity and the like. However, the invention directly uses glycyrrhetinic acid as a reaction raw material, and has high cost. The patent CN111171106A discloses a preparation method of 24-hydroxystearyl glycyrrhetinate, and relates to the fields of foods, cosmetics, medicines and health products; compared with 24-hydroxy-glycyrrhetinic acid, the prepared 24-hydroxy-stearyl glycyrrhetinic acid ester has the advantages that the solubility in grease is obviously changed due to the introduction of lipophilic higher alkanol, and meanwhile, compared with 24-hydroxy-glycyrrhetinic acid, the anti-inflammatory effect is better, the method is suitable for large-scale popularization and application, but the method needs column chromatography purification and is complex to operate. Therefore, there is a need in the market to develop a process for synthesizing stearyl glycyrrhetinate which is low in cost and simple to operate. Disclosure of Invention Aiming at the problems existing in the prior art, the invention aims to provide a green synthesis process of stearyl glycyrrhetinate, which has the advantages of simple process flow, convenient operation, mild reaction conditions, reusable catalyst and product purity of not less than 99.5 percent. In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: the invention provides a process for green synthesis of high-purity stearyl glycyrrhetinate based on enzyme catalysis, which comprises the following steps of: s1, dissolving glycyrrhizic acid or salt thereof in a buffer solution, adding immobilized beta-glucosidase, reacting for 4-6 hours at 40-60 ℃ and 180-250rpm, and performing post-treatment to obtain a glycyrrhizic acid intermediate; S2, adding the glycyrrhetinic acid intermediate, stearyl alcohol and a catalyst obtained in the step S1 into an organic solv