CN115093454B - Co-production preparation method of cholic acid and deoxycholic acid compound - Google Patents
Co-production preparation method of cholic acid and deoxycholic acid compound Download PDFInfo
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- CN115093454B CN115093454B CN202210786175.4A CN202210786175A CN115093454B CN 115093454 B CN115093454 B CN 115093454B CN 202210786175 A CN202210786175 A CN 202210786175A CN 115093454 B CN115093454 B CN 115093454B
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- 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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Abstract
The invention discloses a co-production preparation method of cholic acid and deoxycholic acid compounds, which comprises the following specific steps: heating oxgall and sodium hydroxide to react to obtain a cholic acid A and deoxycholic acid A mixture; reacting the cholic acid A and deoxycholic acid A mixture with petroleum ether to obtain a cholic acid B and deoxycholic acid B mixture; reacting the mixture of cholic acid B and deoxycholic acid B with methanol and triethylamine to obtain cholic acid amine A+deoxycholic acid amine A; dissolving cholic acid amine A in water to obtain cholic acid C; reflux crystallization of cholic acid C and ethyl acetate to obtain cholic acid product; heating and refluxing deoxycholate amine A to prepare deoxycholate triethylamine salt B; dissolving deoxycholic acid triethylamine salt B in water to obtain deoxycholic acid C; deoxycholic acid C reacts with glacial acetic acid, water and methanol to obtain deoxycholic acid. The method of the invention solves the problems of low yield, complex operation, poor feasibility, high impurity content and the like in the independent extraction, and saves resources. The purity of cholic acid and deoxycholic acid prepared by the method of the invention is more than 99 percent.
Description
Technical Field
The invention relates to the technical field of natural product preparation, in particular to a co-production preparation method of cholic acid and deoxycholic acid compounds.
Background
Cholic acid consists of a rigid steroid ring and a fatty side chain, and chemical book is found and its structure determined by the german scientist hai ottowieland, a generic name for a large class of cholanic acids in bile.
Deoxycholic acid is a bile acid with a hydroxyl group on C-7, is free bile acid obtained by the derivative of cholic acid losing one oxygen atom, and mainly exists in the bile in the form of taurine and glycine combination. The method is mainly used for biochemical research, bacteriology and enzymology research; a lipase accelerator; and (3) dissolving the anion remover and the protein.
The preparation method of the existing cholic acid mainly comprises the following steps: preparing crude oxcholic acid, adding 100g/L sodium hydroxide into oxgall or sheep gall, and heating and boiling for 12-18h to obtain saponified solution; cooling, adding acid to adjust pH to 1.0, precipitating cholic acid, taking out cholic acid, decocting in water, rinsing, drying at 75deg.C, and pulverizing to obtain crude taurocholate; cholic acid [ NaOH ] of cattle and sheep]→[100℃,12-18h]Saponification liquid [ H ] 2 SO 4 ]→[pH1,75℃]Crude cholic acid from cattle and sheep; adding 0.5-1 times of 95% ethanol into crude cholic acid, heating and refluxing until solid is dissolved, and cooling; taking out the crystals, mashing, filtering, and washing with 95% ethanol until the filtrate is colorless; adding 4 times of ethanol into the crystals, adding 100-150g/L of active carbon, heating and refluxing until the crystals are dissolved, filtering while the crystals are hot, concentrating the filtrate to 1/4 of the original volume, cooling, crystallizing, filtering, adding ethanol for washing the crystals, and drying to obtain finished products of the taurocholate.
The preparation method of deoxycholic acid mainly comprises the following steps: adding sodium hydroxide and 40% aqueous solution into oxgall solution, stirring at 80-90deg.C for 2 hr, cooling to 20deg.C, filtering, adjusting pH to 1.5 with 50% sulfuric acid at 10deg.C, filtering, collecting precipitate, and washing with water to neutrality. Stirring the wet filter cake at 40 ℃ with a mixed solution of ethyl acetate and benzene (1:1), filtering insoluble substances while the wet filter cake is hot, cooling, and separating out crystals from the solution to obtain a finished product.
Therefore, cholic acid and deoxycholic acid are important natural compounds, the extraction methods of the cholic acid and deoxycholic acid in the prior art are basically independent extraction, a co-production extraction process is not adopted, and the independent extraction has the problems of low yield, complex operation, poor feasibility, resource waste, high impurity content of products and the like.
Disclosure of Invention
In order to solve the technical problems, the invention aims to provide a co-production preparation method of cholic acid and deoxycholic acid compounds.
The invention provides a co-production preparation method of cholic acid and deoxycholic acid compounds, which specifically comprises the following steps:
step 1, adding oxgall into a reaction kettle, stirring, adding sodium hydroxide, heating to a certain temperature, continuing to react at the same temperature for 16 hours, cooling, adding hydrogen peroxide, intermittently stirring, adding 2mol/L sulfuric acid or hydrochloric acid, adjusting the pH value to 2.5, centrifuging, collecting a filter cake, and obtaining a cholic acid A and deoxycholic acid A mixture for later use;
step 2, adding the cholic acid A and deoxycholic acid A mixture obtained in the step 1 and petroleum ether into a reaction kettle, sealing, intermittently stirring for 8 hours, centrifuging, and collecting a filter cake to obtain a cholic acid B and deoxycholic acid B mixture for later use;
step 3, adding the cholic acid B and deoxycholic acid B mixture obtained in the step 2 into a mixed solution of methanol and triethylamine, heating and refluxing for 5 hours, cooling and centrifuging, and collecting filter cakes and filtrate to obtain a solution of cholic acid amine A and deoxycholic acid triethylamine salt A for later use;
step 4, placing the cholic acid amine A obtained in the step 3 into a reaction kettle, adding water for dissolution, filtering, adding 2mol/L sulfuric acid or hydrochloric acid for regulating the pH value to 2.5, centrifuging, and collecting a filter cake to obtain cholic acid C for later use;
step 5, adding the cholic acid C and ethyl acetate obtained in the step 4 into a reaction kettle for reflux crystallization, centrifuging and drying to obtain a cholic acid finished product;
step 6, heating and refluxing the deoxycholic acid triethylamine salt A solution obtained in the step 3 to remove triethylamine and methanol to obtain deoxycholic acid triethylamine salt B for later use;
step 7, adding the deoxycholic acid triethylamine salt B obtained in the step 6 and water into a reaction kettle for dissolution, adding 2mol/L sulfuric acid or hydrochloric acid for adjusting the pH value to 2.5, centrifuging, and collecting a filter cake to obtain deoxycholic acid C for later use;
and 8, adding the deoxycholic acid C obtained in the step 7 into a mixed solution of glacial acetic acid, water and methanol, heating and refluxing for 5 hours, cooling, centrifuging, collecting a filter cake, and drying to obtain a deoxycholic acid finished product.
Further, in the step 1, the weight ratio of the added oxgall to the sodium hydroxide is 0.5-2:0.05-1, wherein the certain temperature is 100-110 ℃.
Optimally, in the step 1, the weight ratio of the added oxgall to the sodium hydroxide is 1:0.09, a certain temperature is preferably 110 ℃.
Further, in the step 2, the weight ratio of the mixture of cholic acid A and deoxycholic acid A to petroleum ether is 0.5-2:1-2.
Optimally, in the step 2, the weight ratio of the mixture of cholic acid A and deoxycholic acid A to petroleum ether is 1:1.5.
further, in the step 3, the weight ratio of the mixture of cholic acid B and deoxycholic acid B to methanol and triethylamine is 0.5-1.5:1.5-3:0.3-0.8.
Optimally, in the step 3, the weight ratio of the mixture of cholic acid B and deoxycholic acid B to methanol and triethylamine is 1:2:0.65.
further, in the step 5, the feeding ratio of cholic acid C and ethyl acetate into the reaction kettle is 0.5-2:1 to 1.8; in the step 8, the weight ratio of the deoxycholic acid C to the glacial acetic acid, the water and the methanol is 0.5-2:1-3:0.2-0.8:0.5-2.
Optimally, in the step 5, the feeding ratio of cholic acid C and ethyl acetate into the reaction kettle is 1:1.65; in the step 8, the weight ratio of the deoxycholic acid C to the glacial acetic acid, the water and the methanol is 1:1.2:0.4:1.
compared with the prior art, the invention has the following beneficial effects:
the method is a co-production extraction process of cholic acid and deoxycholic acid, solves the problems of low yield, complex operation, poor feasibility, high impurity content and the like in the process of independent extraction, and saves resources. The purity of cholic acid and deoxycholic acid prepared by the method is over 99 percent.
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FIG. 1 is a flow chart of the preparation method of the present invention.
Detailed Description
The technical solutions of the present invention will be clearly and completely described in connection with the embodiments, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
A co-production preparation method of cholic acid and deoxycholic acid compounds specifically comprises the following steps:
step 1, 1000g of oxgall is added into a reaction kettle to be stirred, 90g of sodium hydroxide is added to be heated to 110 ℃, the same-temperature reaction is continued for 16 hours, the temperature is reduced, hydrogen peroxide is added, intermittent stirring is carried out, 2mol/L hydrochloric acid is added to be adjusted to pH value to 2.5, centrifugation is carried out, a filter cake is collected, and 65g of cholic acid A and deoxycholic acid A mixture is obtained for standby;
step 2, adding 65g of the cholic acid A and deoxycholic acid A mixture obtained in the step 1 and 97.5g of petroleum ether into a reaction kettle, sealing, intermittently stirring for 8 hours, centrifuging, and collecting a filter cake to obtain 55g of a cholic acid B and deoxycholic acid B mixture for later use;
step 3, adding 55g of the mixture of cholic acid B and deoxycholic acid B obtained in the step 2 into 110g of methanol and 140.75g of triethylamine, heating and refluxing for 5h, cooling and centrifuging, and collecting filter cakes and filtrate to obtain 60g of cholic acid amine A and 140.75g of deoxycholic acid triethylamine salt A solution for later use;
step 4, putting 60g of cholic acid amine A obtained in the step 3 into a reaction kettle, adding water for dissolution, filtering, adding 2mol/L hydrochloric acid for regulating the pH value to 2.5, centrifuging, and collecting a filter cake to obtain 40g of cholic acid C for later use;
step 5, adding 40g of cholic acid C obtained in the step 4 and 66g of ethyl acetate into a reaction kettle for reflux crystallization, centrifuging, and drying to obtain 36.5g of cholic acid finished product, wherein the purity can reach 99.57%, and the cholic acid finished product meets the medicinal standard;
step 6, heating and refluxing 140.75g of deoxycholic acid triethylamine salt A solution obtained in the step 3 to remove triethylamine and methanol to obtain 15g of deoxycholic acid triethylamine salt B for later use;
step 7, adding 15g of deoxycholic acid triethylamine salt B obtained in the step 6 and water into a reaction kettle for dissolution, adding 2mol/L hydrochloric acid to adjust the pH value to 2.5, centrifuging, and collecting a filter cake to obtain 10g of deoxycholic acid C for later use;
and 8, adding 12g of glacial acetic acid, 4g of water and 10g of methanol into 10g of deoxycholic acid C obtained in the step 7, heating and refluxing for 5 hours, cooling, centrifuging, collecting a filter cake, and drying to obtain 6.1g of deoxycholic acid finished product, wherein the purity can reach 99.36%.
Example 2
A co-production preparation method of cholic acid and deoxycholic acid compounds specifically comprises the following steps:
step 1, adding 800g of oxgall into a reaction kettle, stirring, adding 72g of sodium hydroxide, heating to 100 ℃, continuing to react at the same temperature for 16 hours, cooling, adding hydrogen peroxide, intermittently stirring, adding 2mol/L of sulfuric acid, adjusting the pH value to 2.5, centrifuging at a speed of 800 revolutions per minute, and collecting a filter cake to obtain 44g of cholic acid A and deoxycholic acid A mixture for later use;
step 2, adding 44g of the cholic acid A and deoxycholic acid A mixture obtained in the step 1 and 78g of petroleum ether into a reaction kettle, sealing, intermittently stirring for 8 hours, centrifuging, and collecting a filter cake to obtain 44g of a cholic acid B and deoxycholic acid B mixture for later use;
step 3, adding 44g of the cholic acid B and deoxycholic acid B mixture obtained in the step 2 into 88g of methanol and 28.6g of triethylamine, heating and refluxing for 5h, cooling and centrifuging, and collecting filter cakes and filtrate to obtain 48g of cholic acid amine A and 112.6g of deoxycholic acid triethylamine salt A solution for later use;
step 4, putting 48g of cholic acid amine A obtained in the step 3 into a reaction kettle, adding water for dissolution, filtering, adding 2mol/L sulfuric acid for regulating the pH value to 2.5, centrifuging, and collecting a filter cake to obtain 32g of cholic acid C for later use;
step 5, adding 32g of cholic acid C obtained in the step 4 and 52.8g of ethyl acetate into a reaction kettle for reflux crystallization, centrifuging, and drying to obtain 29.2g of cholic acid finished product, wherein the purity can reach 99.32%, and the product meets the medicinal standard;
step 6, heating and refluxing 112.6g of the deoxycholic acid triethylamine salt A solution obtained in the step 3 to remove triethylamine and methanol to obtain 12g of deoxycholic acid triethylamine salt B for later use;
step 7, adding 12g of deoxycholic acid triethylamine salt B obtained in the step 6 and water into a reaction kettle for dissolution, adding 2mol/L sulfuric acid to adjust the pH value to 2.5, centrifuging, and collecting a filter cake to obtain 8g of deoxycholic acid C for later use;
and 8, adding 9.6g of glacial acetic acid, 3.2g of water and 8g of methanol into 8g of deoxycholic acid C obtained in the step 7, heating and refluxing for 5 hours, cooling, centrifuging, collecting a filter cake, and drying to obtain 4.9g of deoxycholic acid finished product, wherein the purity can reach 99.25%.
Example 3
A co-production preparation method of cholic acid and deoxycholic acid compounds specifically comprises the following steps:
step 1, adding 1200g of oxgall into a reaction kettle, stirring, adding 108g of sodium hydroxide, heating to 110 ℃, continuing to react at the same temperature for 16 hours, cooling, adding hydrogen peroxide, intermittently stirring, adding 2mol/L hydrochloric acid, adjusting the pH value to 2.5, centrifuging, collecting a filter cake, and obtaining 78g of a cholic acid A and deoxycholic acid A mixture for later use;
step 2, adding 78g of the cholic acid A and deoxycholic acid A mixture obtained in the step 1 and 117g of petroleum ether into a reaction kettle, sealing, intermittently stirring for 8 hours, centrifuging, and collecting a filter cake to obtain 66g of a cholic acid B and deoxycholic acid B mixture for later use;
step 3, adding 66g of the mixture of cholic acid B and deoxycholic acid B obtained in the step 2 into 132g of methanol and 42.9g of triethylamine, heating and refluxing for 5h, cooling and centrifuging, and collecting filter cakes and filtrate to obtain 72g of cholic acid amine A and 153.5g of deoxycholic acid triethylamine salt A solution for later use;
step 4, putting 72g of cholic acid amine A obtained in the step 3 into a reaction kettle, adding water for dissolution, filtering, adding 2mol/L hydrochloric acid for regulating the pH value to 2.5, centrifuging, and collecting a filter cake to obtain 48g of cholic acid C for later use;
step 5, adding 48g of cholic acid C obtained in the step 4 and 79.2g of ethyl acetate into a reaction kettle for reflux crystallization, centrifuging, and drying to obtain 43.8g of cholic acid finished product, wherein the purity can reach 99.45%, and the product meets the medicinal standard;
step 6, heating and refluxing 153.5g of deoxycholic acid triethylamine salt A solution obtained in the step 3 to remove triethylamine and methanol to obtain 16.4g of deoxycholic acid triethylamine salt B for later use;
step 7, adding 16.4g of deoxycholic acid triethylamine salt B obtained in the step 6 and water into a reaction kettle for dissolution, adding 2mol/L hydrochloric acid to adjust the pH value to 2.5, centrifuging, and collecting a filter cake to obtain 11g of deoxycholic acid C for later use;
and 8, adding 13.2g of glacial acetic acid, 4.4g of water and 11g of methanol into 11g of deoxycholic acid C obtained in the step 7, heating and refluxing for 5 hours, cooling, centrifuging, collecting a filter cake, and drying to obtain 6.7g of deoxycholic acid finished product, wherein the purity can reach 99.30%.
Example 4
A co-production preparation method of cholic acid and deoxycholic acid compounds specifically comprises the following steps:
step 1, adding 500g of oxgall into a reaction kettle, stirring, adding 50g of sodium hydroxide, heating to 100 ℃, continuously reacting at the same temperature for 14 hours, cooling, adding hydrogen peroxide, intermittently stirring, adding 2mol/L sulfuric acid to adjust the pH value to 2, centrifuging, and collecting a filter cake to obtain 32.5g of a cholic acid A and deoxycholic acid A mixture for later use;
step 2, adding 32.5g of the cholic acid A and deoxycholic acid A mixture obtained in the step 1 and 65g of petroleum ether into a reaction kettle, sealing, intermittently stirring for 6 hours, centrifuging, and collecting a filter cake to obtain 27.5g of a cholic acid B and deoxycholic acid B mixture for later use;
step 3, adding 27.5g of the mixture of cholic acid B and deoxycholic acid B obtained in the step 2 into 82.5g of methanol and 16.5g of triethylamine, heating and refluxing for 3h, cooling and centrifuging, and collecting filter cakes and filtrate to obtain 30g of cholic acid amine A and 70.4g of deoxycholic acid triethylamine salt A solution for later use;
step 4, putting 30g of cholic acid amine A obtained in the step 3 into a reaction kettle, adding water for dissolution, filtering, adding 2mol/L sulfuric acid for regulating the pH value to 2, centrifuging, and collecting a filter cake to obtain 20g of cholic acid C for later use;
step 5, adding 20g of cholic acid C obtained in the step 4 and 40g of ethyl acetate into a reaction kettle for reflux crystallization, centrifuging, and drying to obtain 18.25g of cholic acid finished product, wherein the purity can reach 99.40%, and the product meets the medicinal standard;
step 6, heating and refluxing 70.4g of the deoxycholic acid triethylamine salt A solution obtained in the step 3 to remove triethylamine and methanol to obtain 7.5g of deoxycholic acid triethylamine salt B for later use;
step 7, adding 7.5g of deoxycholic acid triethylamine salt B obtained in the step 6 and water into a reaction kettle for dissolution, adding 2mol/L sulfuric acid to adjust the pH value to 2, centrifuging, and collecting a filter cake to obtain 5g of deoxycholic acid C for later use;
and 8, adding 10g of glacial acetic acid, 2g of water and 5g of methanol into 5g of deoxycholic acid C obtained in the step 7, heating and refluxing for 3 hours, cooling, centrifuging, collecting a filter cake, and drying to obtain 3.1g of deoxycholic acid finished product, wherein the purity can reach 99.16%.
Example 5
A co-production preparation method of cholic acid and deoxycholic acid compounds specifically comprises the following steps:
step 1, adding 1400g of oxgall into a reaction kettle, stirring, adding 700g of sodium hydroxide, heating to 100 ℃, continuing to react at the same temperature for 18 hours, cooling, adding hydrogen peroxide, intermittently stirring, adding 2mol/L sulfuric acid to adjust the pH value to 4, centrifuging, and collecting a filter cake to obtain 91g of a cholic acid A and deoxycholic acid A mixture for later use;
step 2, adding 91g of the cholic acid A and deoxycholic acid A mixture obtained in the step 1 and 91g of petroleum ether into a reaction kettle, sealing, intermittently stirring for 10 hours, centrifuging, and collecting a filter cake to obtain 77g of a cholic acid B and deoxycholic acid B mixture for later use;
step 3, adding 77g of the mixture of cholic acid B and deoxycholic acid B obtained in the step 2 into 154g of methanol and 40.8g of triethylamine, heating and refluxing for 7h, cooling and centrifuging, and collecting filter cakes and filtrate to obtain 84g of cholic acid amine A and 197.05g of deoxycholic acid triethylamine salt A solution for later use;
step 4, putting 84g of cholic acid amine A obtained in the step 3 into a reaction kettle, adding water for dissolution, filtering, adding 2mol/L sulfuric acid for regulating the pH value to 4, centrifuging, and collecting a filter cake to obtain 56g of cholic acid C for later use;
step 5, adding 56g of cholic acid C obtained in the step 4 and 50.4g of ethyl acetate into a reaction kettle for reflux crystallization, centrifuging, and drying to obtain 51.1g of cholic acid finished product, wherein the purity can reach 99.24%, and the product meets the medicinal standard;
step 6, heating and refluxing 197.05g of deoxycholic acid triethylamine salt A solution obtained in the step 3 to remove triethylamine and methanol to obtain 21g of deoxycholic acid triethylamine salt B for later use;
step 7, adding 21g of deoxycholic acid triethylamine salt B obtained in the step 6 and water into a reaction kettle for dissolution, adding 2mol/L sulfuric acid to adjust the pH value to 4, centrifuging, and collecting a filter cake to obtain 14g of deoxycholic acid C for later use;
and 8, adding 21g of glacial acetic acid, 5.6g of water and 14g of methanol into 14g of deoxycholic acid C obtained in the step 7, heating and refluxing for 7h, cooling, centrifuging, collecting a filter cake, and drying to obtain 8.54g of deoxycholic acid finished product with the purity of 99.20%.
Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (9)
1. A co-production preparation method of cholic acid and deoxycholic acid compounds is characterized by comprising the following steps:
step 1, adding oxgall into a reaction kettle, stirring, adding sodium hydroxide, heating to a certain temperature, continuing to react at the same temperature for 16 hours, cooling, adding hydrogen peroxide, intermittently stirring, adding 2mol/L sulfuric acid or hydrochloric acid, adjusting the pH value to 2.5, centrifuging, collecting a filter cake, and obtaining a cholic acid A and deoxycholic acid A mixture for later use;
step 2, adding the cholic acid A and deoxycholic acid A mixture obtained in the step 1 and petroleum ether into a reaction kettle, sealing, intermittently stirring for 8 hours, centrifuging, and collecting a filter cake to obtain a cholic acid B and deoxycholic acid B mixture for later use;
step 3, adding the cholic acid B and deoxycholic acid B mixture obtained in the step 2 into a mixed solution of methanol and triethylamine, heating and refluxing for 5 hours, cooling and centrifuging, and collecting filter cakes and filtrate to obtain a solution of cholic acid amine A and deoxycholic acid triethylamine salt A for later use;
step 4, placing the cholic acid amine A obtained in the step 3 into a reaction kettle, adding water for dissolution, filtering, adding 2mol/L sulfuric acid or hydrochloric acid for regulating the pH value to 2.5, centrifuging, and collecting a filter cake to obtain cholic acid C for later use;
step 5, adding the cholic acid C and ethyl acetate obtained in the step 4 into a reaction kettle for reflux crystallization, centrifuging and drying to obtain a cholic acid finished product;
step 6, heating and refluxing the deoxycholic acid triethylamine salt A solution obtained in the step 3 to remove triethylamine and methanol to obtain deoxycholic acid triethylamine salt B for later use;
step 7, adding the deoxycholic acid triethylamine salt B obtained in the step 6 and water into a reaction kettle for dissolution, adding 2mol/L sulfuric acid or hydrochloric acid for adjusting the pH value to 2.5, centrifuging, and collecting a filter cake to obtain deoxycholic acid C for later use;
and 8, adding the deoxycholic acid C obtained in the step 7 into a mixed solution of glacial acetic acid, water and methanol, heating and refluxing for 5 hours, cooling, centrifuging, collecting a filter cake, and drying to obtain a deoxycholic acid finished product.
2. The method for co-production of cholic acid and deoxycholic acid compound according to claim 1, wherein in the step 1, the weight ratio of the added oxgall to the sodium hydroxide is 0.5-2:0.05-1, wherein the certain temperature is 100-110 ℃.
3. The method for co-production of cholic acid and deoxycholic acid compound according to claim 2, wherein in the step 1, the weight ratio of the added oxgall to sodium hydroxide is 1:0.09, said certain temperature preferably being 110 ℃.
4. The method for co-production of cholic acid and deoxycholic acid compound according to claim 1, wherein in the step 2, the weight ratio of the mixture of cholic acid a and deoxycholic acid a to petroleum ether is 0.5-2:1-2.
5. The method for co-production of cholic acid and deoxycholic acid compound according to claim 4, wherein in the step 2, the weight ratio of the mixture of cholic acid a and deoxycholic acid a to petroleum ether is 1:1.5.
6. the method for co-production preparation of cholic acid and deoxycholic acid compound according to claim 1, wherein in the step 3, the weight ratio of the mixture of cholic acid B and deoxycholic acid B to methanol and triethylamine is 0.5-1.5:1.5-3:0.3-0.8.
7. The method for co-production of cholic acid and deoxycholic acid compound according to claim 6, wherein in the step 3, the weight ratio of the mixture of cholic acid B and deoxycholic acid B to methanol and triethylamine is 1:2:0.65.
8. the method for co-production preparation of cholic acid and deoxycholic acid compound according to claim 1, wherein in the step 5, the feeding ratio of cholic acid C and ethyl acetate into the reaction kettle is 0.5-2:1 to 1.8; in the step 8, the weight ratio of the deoxycholic acid C to the glacial acetic acid, the water and the methanol is 0.5-2:1-3:0.2-0.8:0.5-2.
9. The method for co-production preparation of cholic acid and deoxycholic acid compound according to claim 8, wherein in the step 5, the feeding ratio of cholic acid C to ethyl acetate into the reaction kettle is 1:1.65; in the step 8, the weight ratio of the deoxycholic acid C to the glacial acetic acid, the water and the methanol is 1:1.2:0.4:1.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB695504A (en) * | 1950-10-18 | 1953-08-12 | Drug Res Inc | Method of isolating and purifying cholic and desoxycholic acids |
| US2661356A (en) * | 1951-06-13 | 1953-12-01 | Armour & Co | Separation of bile acids |
| CN109810159A (en) * | 2019-01-22 | 2019-05-28 | 常德云港生物科技有限公司 | A kind of method that allocholic acid yield can be improved from duck bile |
| CN114369132A (en) * | 2021-11-19 | 2022-04-19 | 四川澄华生物科技有限公司 | Preparation method of deoxycholic acid |
-
2022
- 2022-07-04 CN CN202210786175.4A patent/CN115093454B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB695504A (en) * | 1950-10-18 | 1953-08-12 | Drug Res Inc | Method of isolating and purifying cholic and desoxycholic acids |
| US2661356A (en) * | 1951-06-13 | 1953-12-01 | Armour & Co | Separation of bile acids |
| CN109810159A (en) * | 2019-01-22 | 2019-05-28 | 常德云港生物科技有限公司 | A kind of method that allocholic acid yield can be improved from duck bile |
| CN114369132A (en) * | 2021-11-19 | 2022-04-19 | 四川澄华生物科技有限公司 | Preparation method of deoxycholic acid |
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| CN115093454A (en) | 2022-09-23 |
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