CN113150055A - High-efficiency synthesis method of stigmasterol ester - Google Patents
High-efficiency synthesis method of stigmasterol ester Download PDFInfo
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- CN113150055A CN113150055A CN202110347634.4A CN202110347634A CN113150055A CN 113150055 A CN113150055 A CN 113150055A CN 202110347634 A CN202110347634 A CN 202110347634A CN 113150055 A CN113150055 A CN 113150055A
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- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
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- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
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Abstract
The invention discloses a high-efficiency synthesis method of stigmasterol ester, which comprises the steps of adding stigmasterol, fatty acid and a metalloporphyrin catalyst into a reactor according to the molar ratio of 1:1-2:0.01-0.05, and catalyzing esterification reaction to obtain an esterification product; filtering the esterification product, adding PBS buffer solution to neutralize to neutrality, adsorbing and purifying, adding column chromatography to the purified product, eluting with eluent, concentrating under reduced pressure to recover eluent, and drying to obtain final product. The synthesis method disclosed by the invention has the characteristics of high conversion rate of the stigmasterol ester and high product purity, has the advantages of easiness in recycling the catalyst, no toxicity, harmlessness, environmental friendliness, high production efficiency, simple process, low production cost, less discharge of three wastes and the like, has good social efficiency, economic benefit and ecological benefit, and can be widely applied to the fields of medicines, foods and health-care products.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to a high-efficiency synthesis method of stigmasterol ester.
Background
Stigmasterol (stigmaster01), C29H450. The phytosterol has a molecular weight of 412, is also called stigmasta-5, 22-diene-3 beta-alcohol or 24R-ethyl cholest-5, 22-diene-3 beta-alcohol, is a phytosterol and widely exists in various plants. Stigmasterol has obvious pharmacological activities of resisting oxidation, resisting tumor, resisting cardiovascular disease, protecting liver, resisting inflammation and preventing cancer, etc., and is applied in medicine, food, chemical industry and other industries.
Along with the improvement of the living standard of people, the concomitant cardiovascular and cerebrovascular diseases such as hyperlipidemia and hypertension increasingly affect and harm the life and the body health of people, and the morbidity of the cardiovascular and cerebrovascular diseases accounts for the first reason of death of people in China. Soyasterol is a novel functional active component for reducing serum cholesterol and preventing and treating cardiovascular diseases, and has similar biochemical characteristics to cholesterol. Stigmasterol cannot be synthesized in human body and can only be taken by diet, but because most of phytosterol is almost insoluble in water and has low solubility in oil, the solubility of stigmasterol is generally less than 2% at 40 ℃, so that the application of stigmasterol in food and health care products is limited. In order to overcome the defect, sterol is esterified currently, and the solubility of the obtained stigmasterol ester product in water or oil is obviously improved.
The current synthesis method of stigmasterol ester mainly comprises the following steps: the stigmasterol and the fatty acid or the fatty acid methyl ester are synthesized under the chemical catalysis or the biological enzyme catalysis. Strong acid, strong base, toxic and harmful substances exist in the catalyst used in the chemical synthesis, and the addition of the substances can easily generate byproducts and generate toxic and harmful substances in violent chemical reaction, so that the synthesized stigmasterol ester is difficult to apply to foods, medicines and health care products, and the used chemical catalyst is difficult to separate from the product and recover the catalyst; and the problems of more complex synthesis process, higher cost, lower efficiency, low yield of the stigmasterol ester and the like exist. Therefore, a high-efficiency, high-yield, green and environment-friendly synthetic method of phytosterol ester is urgently needed.
The above background disclosure is only for the purpose of assisting understanding of the inventive concept and technical solutions of the present invention, and does not necessarily belong to the prior art of the present patent application, and should not be used for evaluating the novelty and inventive step of the present application in the case that there is no clear evidence that the above content is disclosed at the filing date of the present patent application.
Disclosure of Invention
The invention provides a high-efficiency synthesis method of stigmasterol ester aiming at the problems in the existing stigmasterol ester synthesis. The synthesis method disclosed by the invention has the characteristics of high conversion rate of the stigmasterol ester and high product purity, has the advantages of easiness in recycling the catalyst, no toxicity, harmlessness, environmental friendliness, high production efficiency, simple process, low production cost, less discharge of three wastes and the like, has good social efficiency, economic benefit and ecological benefit, and can be widely applied to the fields of medicines, foods and health-care products.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
a high-efficiency synthesis method of stigmasterol ester comprises the following steps:
s1, adding stigmasterol, fatty acid and a metalloporphyrin catalyst into a reactor according to the molar ratio of 1:1-2:0.01-0.05, and carrying out catalytic esterification reaction to obtain an esterification product;
s2, filtering the esterification product, adding PBS buffer solution to neutralize to be neutral, adsorbing and purifying, adding column chromatography to the purified product, eluting with eluent, decompressing and concentrating to recover the eluent, and drying to obtain the final product.
As further optimization of the scheme of the invention: the fatty acid comprises one or more of oleic acid, linoleic acid, lauric acid, palmitic acid, stearic acid, myristic acid, caproic acid and caprylic acid.
As further optimization of the scheme of the invention: the metalloporphyrin catalyst comprises one or more of tetra (pentafluorophenyl) cobalt porphyrin, tetra (4-nitrophenyl) cobalt porphyrin and tetra (p-sulfophenyl) manganese porphyrin.
As further optimization of the scheme of the invention: the catalytic esterification reaction is carried out for 6-12h at the temperature of 60-80 ℃.
As further optimization of the scheme of the invention: the adsorption purification is to add alkaline calcium bentonite and stir for 10-20min for adsorption. The addition amount of the alkaline calcium bentonite is 1-3% of the mass of the esterification product.
As further optimization of the scheme of the invention: the pH of the PBS buffer was 8.5.
As further optimization of the scheme of the invention: the column chromatography is silica gel column chromatography or polyacrylamide gel column chromatography.
As further optimization of the scheme of the invention: the eluent is acetone and ethyl acetate with the volume ratio of 3-5: 1.
Compared with the prior art, the invention has the advantages and beneficial effects that:
1. the synthesis method disclosed by the invention has the characteristics of high conversion rate of the stigmasterol ester and high product purity, has the advantages of easiness in recycling the catalyst, no toxicity, harmlessness, environmental friendliness, high production efficiency, simple process, low production cost, less discharge of three wastes and the like, has good social efficiency, economic benefit and ecological benefit, and can be widely applied to the fields of medicines, foods and health-care products.
2. The method takes metalloporphyrin as the enzyme-like catalyst, has the advantages of large porous specific surface area, high catalytic efficiency, high catalytic activity, high selectivity, mild reaction conditions, easy recovery, repeated cyclic utilization, no toxicity, no corrosion and the like, can efficiently catalyze the synthesis of the stigmasterol ester, and improves the efficiency and the yield of the stigmasterol ester and the esterification reaction.
3. The method comprises the steps of neutralizing the residual unreacted fatty acid in PBS buffer solution, adsorbing and purifying with alkaline calcium bentonite, performing column chromatography with silica gel or polyacrylamide gel column, and eluting with acetone and ethyl acetate, thereby improving the product purity of the stigmasterol ester.
Detailed Description
The technical solutions of the present invention will be clearly and completely described below with reference to specific embodiments, but the scope of the present invention is not limited thereto.
Example 1
A high-efficiency synthesis method of stigmasterol ester comprises the following steps:
s1, adding stigmasterol, oleic acid and tetra (4-nitrophenyl) cobalt porphyrin according to the molar ratio of 1:1.5:0.03 into a reactor, and carrying out catalytic esterification reaction for 8 hours at the temperature of 75 ℃ to obtain an esterification product;
s2, filtering the esterification product, adding PBS buffer solution with the PH of 8.5 to neutralize to be neutral, adding alkaline calcium bentonite with the mass of 2% of that of the esterification product, stirring for 15min, filtering, adding the product into silica gel column chromatography, eluting by acetone and ethyl acetate eluent with the volume ratio of 3:1, decompressing, concentrating and recovering the eluent, and drying in an oven with the temperature of 120 ℃ until the water content is less than or equal to 5% to obtain the stigmasterol ester.
The conversion rate of the stigmasterol ester in the example is calculated to reach 98.73%, and the purity of the stigmasterol ester is measured to reach 99.31% by GC-MS.
Example 2
A high-efficiency synthesis method of stigmasterol ester comprises the following steps:
s1, adding stigmasterol, caprylic acid and tetra (p-sulfophenyl) manganoporphyrin into a reactor according to the molar ratio of 1:2:0.04, and carrying out catalytic esterification reaction for 12 hours at the temperature of 65 ℃ to obtain an esterification product;
s2, filtering the esterification product, adding PBS buffer solution with the PH of 8.5 to neutralize to be neutral, adding alkaline calcium bentonite with the mass of 1.5 percent of the esterification product, stirring for 20min, filtering, adding the product into silica gel column chromatography, eluting by acetone and ethyl acetate eluent with the volume ratio of 4:1, decompressing, concentrating and recovering the eluent, and drying in an oven with the temperature of 110 ℃ until the water content is less than or equal to 5 percent to obtain the stigmasterol ester.
The conversion rate of the stigmasterol ester in the example is calculated to reach 98.83%, and the purity of the stigmasterol ester is measured by GC-MS to reach 99.12%.
Example 3
A high-efficiency synthesis method of stigmasterol ester comprises the following steps:
s1, adding stigmasterol, linoleic acid and tetra (p-sulfophenyl) manganoporphyrin into a reactor according to the molar ratio of 1:1.2:0.05, and carrying out catalytic esterification reaction for 9 hours at the temperature of 70 ℃ to obtain an esterification product;
s2, filtering the esterification product, adding PBS buffer solution with the PH of 8.5 to neutralize to be neutral, adding alkaline calcium bentonite with the mass of 2.5 percent of the esterification product, stirring for 10min, filtering, adding the product into silica gel column chromatography, eluting by acetone and ethyl acetate eluent with the volume ratio of 2:1, decompressing, concentrating and recovering the eluent, and drying in an oven with the temperature of 110 ℃ until the water content is less than or equal to 5 percent to obtain the stigmasterol ester.
The conversion rate of the stigmasterol ester in the example is 97.32% by calculation, and the purity of the stigmasterol ester is 98.97% by GC-MS measurement.
Example 4
A high-efficiency synthesis method of stigmasterol ester comprises the following steps:
s1, adding stigmasterol, oleic acid and tetra (pentafluorophenyl) cobalt porphyrin into a reactor according to the molar ratio of 1:1.3:0.04, and carrying out catalytic esterification reaction at 80 ℃ for 10 hours to obtain an esterification product;
s2, filtering the esterification product, adding PBS buffer solution with the PH of 8.5 to neutralize to be neutral, adding alkaline calcium bentonite with the mass of 2% of the esterification product, stirring for 10min, filtering, adding the product into polyacrylamide gel column chromatography, eluting with acetone and ethyl acetate eluent with the volume ratio of 3:1, decompressing, concentrating and recovering the eluent, and drying in an oven with the temperature of 125 ℃ until the water content is less than or equal to 5% to obtain the stigmasterol ester.
The conversion rate of the stigmasterol ester in the example is calculated to reach 98.73%, and the purity of the stigmasterol ester is measured by GC-MS to reach 99.37%.
Example 5
A high-efficiency synthesis method of stigmasterol ester comprises the following steps:
s1, adding stigmasterol, palmitic acid and tetra (p-sulfophenyl) manganoporphyrin into a reactor according to the molar ratio of 1:2:0.04, and carrying out catalytic esterification reaction for 12 hours at the temperature of 60 ℃ to obtain an esterification product;
s2, filtering the esterification product, adding PBS buffer solution with the PH of 8.5 to neutralize to be neutral, adding alkaline calcium bentonite with the mass of 3% of that of the esterification product, stirring for 10min, filtering, adding the product into polyacrylamide gel column chromatography, eluting with acetone and ethyl acetate eluent with the volume ratio of 3:1, decompressing, concentrating and recovering the eluent, and drying in an oven with the temperature of 125 ℃ until the water content is less than or equal to 5% to obtain the stigmasterol ester.
The conversion rate of the stigmasterol ester in the example is 98.24% by calculation, and the purity of the stigmasterol ester is 99.06% by GC-MS measurement.
Example 6
A high-efficiency synthesis method of stigmasterol ester comprises the following steps:
s1, adding stigmasterol, lauric acid and tetra (4-nitrophenyl) cobalt porphyrin according to the molar ratio of 1:1.3:0.02 into a reactor, and carrying out catalytic esterification reaction for 12 hours at the temperature of 80 ℃ to obtain an esterification product;
s2, filtering the esterification product, adding PBS buffer solution with the PH of 8.5 to neutralize to be neutral, adding alkaline calcium bentonite with the mass of 1.5% of the esterification product, stirring for 15min, filtering, adding the product into silica gel column chromatography, eluting with acetone and ethyl acetate eluent with the volume ratio of 3:1, decompressing, concentrating and recovering the eluent, and drying in an oven with the temperature of 110 ℃ until the water content is less than or equal to 5% to obtain the stigmasterol ester.
The conversion rate of the stigmasterol ester in the example is calculated to reach 98.33%, and the purity of the stigmasterol ester is 99.16% by GC-MS measurement.
The foregoing is a more detailed description of the invention in connection with specific/preferred embodiments and is not intended to limit the practice of the invention to those descriptions. It will be apparent to those skilled in the art that various substitutions and modifications can be made to the described embodiments without departing from the spirit of the invention, and such substitutions and modifications are to be considered as within the scope of the invention.
Claims (9)
1. The high-efficiency synthesis method of the stigmasterol ester is characterized by comprising the following steps:
s1, adding stigmasterol, fatty acid and a metalloporphyrin catalyst into a reactor according to the molar ratio of 1:1-2:0.01-0.05, and carrying out catalytic esterification reaction to obtain an esterification product;
s2, filtering the esterification product, adding PBS buffer solution to neutralize to be neutral, adsorbing and purifying, adding column chromatography to the purified product, eluting with eluent, decompressing and concentrating to recover the eluent, and drying to obtain the final product.
2. The method for efficiently synthesizing stigmasterol ester according to claim 1, wherein: the fatty acid comprises one or more of oleic acid, linoleic acid, lauric acid, palmitic acid, stearic acid, myristic acid, caproic acid and caprylic acid.
3. The method for efficiently synthesizing stigmasterol ester according to claim 1, wherein: the metalloporphyrin catalyst comprises one or more of tetra (pentafluorophenyl) cobalt porphyrin, tetra (4-nitrophenyl) cobalt porphyrin and tetra (p-sulfophenyl) manganese porphyrin.
4. The method for efficiently synthesizing stigmasterol ester according to claim 3, wherein: the catalytic esterification reaction is carried out for 6-12h at the temperature of 60-80 ℃.
5. The method for efficiently synthesizing stigmasterol ester according to claim 1, wherein: the adsorption purification is to add alkaline calcium bentonite and stir for 10-20 min.
6. The method for efficiently synthesizing stigmasterol ester according to claim 5, wherein: the addition amount of the alkaline calcium bentonite is 1-3% of the mass of the esterification product.
7. The method for efficiently synthesizing stigmasterol ester according to claim 1, wherein: the pH of the PBS buffer was 8.5.
8. The method for efficiently synthesizing stigmasterol ester according to claim 1, wherein: the column chromatography is silica gel column chromatography or polyacrylamide gel column chromatography.
9. The method for efficiently synthesizing stigmasterol ester according to claim 1, wherein: the eluent is acetone and ethyl acetate with the volume ratio of 3-5: 1.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003081994A (en) * | 2001-09-11 | 2003-03-19 | Yashiro:Kk | Method of preparation for high-purity sterol or sterol/ steryl ester mixture |
| CN101235067A (en) * | 2008-01-11 | 2008-08-06 | 浙江工业大学 | Process for preparing plant sterol ester |
| CN102190700A (en) * | 2010-03-12 | 2011-09-21 | 丰益(上海)生物技术研发中心有限公司 | Method for preparing fatty acid phytosterol esters |
| CN104177467A (en) * | 2014-08-07 | 2014-12-03 | 杭州余杭博士达油脂有限公司 | Efficient synthesis and separation method of phytosterol ester |
| US20150025130A1 (en) * | 2012-02-02 | 2015-01-22 | Beijing Peking University Wbl Biotech Co., Ltd. | Sterol derivative, preparation method therefor and use thereof |
| CN108796023A (en) * | 2018-07-04 | 2018-11-13 | 江南大学 | A kind of preparation method of high-purity vegetable sterol monomeric ester |
| CN111187800A (en) * | 2020-03-05 | 2020-05-22 | 山东德普化工科技有限公司 | Method for efficiently synthesizing phytosterol ester by enzyme method |
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- 2021-03-31 CN CN202110347634.4A patent/CN113150055B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003081994A (en) * | 2001-09-11 | 2003-03-19 | Yashiro:Kk | Method of preparation for high-purity sterol or sterol/ steryl ester mixture |
| CN101235067A (en) * | 2008-01-11 | 2008-08-06 | 浙江工业大学 | Process for preparing plant sterol ester |
| CN102190700A (en) * | 2010-03-12 | 2011-09-21 | 丰益(上海)生物技术研发中心有限公司 | Method for preparing fatty acid phytosterol esters |
| US20150025130A1 (en) * | 2012-02-02 | 2015-01-22 | Beijing Peking University Wbl Biotech Co., Ltd. | Sterol derivative, preparation method therefor and use thereof |
| CN104177467A (en) * | 2014-08-07 | 2014-12-03 | 杭州余杭博士达油脂有限公司 | Efficient synthesis and separation method of phytosterol ester |
| CN108796023A (en) * | 2018-07-04 | 2018-11-13 | 江南大学 | A kind of preparation method of high-purity vegetable sterol monomeric ester |
| CN111187800A (en) * | 2020-03-05 | 2020-05-22 | 山东德普化工科技有限公司 | Method for efficiently synthesizing phytosterol ester by enzyme method |
Non-Patent Citations (2)
| Title |
|---|
| AMANDA E. HARGROVE,ET AL: "Boronic Acid Porphyrin Receptor for Ginsenoside Sensing" * |
| DEVARAJ ANANDKUMAR,ET AL: "Synthesis, photophysical properties and anticancer activity of micro-environment sensitive amphiphilic bile acid dendrimers" * |
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