CN114349810A - 甾类化合物通用的手性拆分方法 - Google Patents
甾类化合物通用的手性拆分方法 Download PDFInfo
- Publication number
- CN114349810A CN114349810A CN202111652189.9A CN202111652189A CN114349810A CN 114349810 A CN114349810 A CN 114349810A CN 202111652189 A CN202111652189 A CN 202111652189A CN 114349810 A CN114349810 A CN 114349810A
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- CN
- China
- Prior art keywords
- steroid
- steroid compound
- reaction
- chiral resolution
- heating
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- -1 steroid compounds Chemical class 0.000 title claims abstract description 72
- 238000000034 method Methods 0.000 title claims abstract description 30
- 150000003431 steroids Chemical class 0.000 claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- 239000000126 substance Substances 0.000 claims abstract description 10
- 150000002148 esters Chemical class 0.000 claims abstract description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 28
- 238000010438 heat treatment Methods 0.000 claims description 24
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- 239000012065 filter cake Substances 0.000 claims description 20
- 238000003756 stirring Methods 0.000 claims description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 238000004809 thin layer chromatography Methods 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 239000000243 solution Substances 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 238000001914 filtration Methods 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 12
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 11
- 238000005406 washing Methods 0.000 claims description 11
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 238000012544 monitoring process Methods 0.000 claims description 4
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 229960000583 acetic acid Drugs 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- 239000012362 glacial acetic acid Substances 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 238000009776 industrial production Methods 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 abstract description 2
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 33
- 229960001661 ursodiol Drugs 0.000 description 31
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 26
- 239000000047 product Substances 0.000 description 5
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- CEBVKFVONMPTSV-UHFFFAOYSA-N acetic acid;dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O.CC(O)=O CEBVKFVONMPTSV-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 210000000941 bile Anatomy 0.000 description 2
- RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 description 2
- 229960001091 chenodeoxycholic acid Drugs 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 230000031200 bile acid secretion Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229940097217 cardiac glycoside Drugs 0.000 description 1
- 239000002368 cardiac glycoside Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 201000001883 cholelithiasis Diseases 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- 229920001940 conductive polymer Polymers 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 208000001130 gallstones Diseases 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229930002534 steroid glycoside Natural products 0.000 description 1
- 150000008143 steroidal glycosides Chemical class 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B57/00—Separation of optically-active compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Abstract
Description
Claims (10)
Priority Applications (1)
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CN202111652189.9A CN114349810A (zh) | 2021-12-30 | 2021-12-30 | 甾类化合物通用的手性拆分方法 |
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CN202111652189.9A CN114349810A (zh) | 2021-12-30 | 2021-12-30 | 甾类化合物通用的手性拆分方法 |
Publications (1)
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CN114349810A true CN114349810A (zh) | 2022-04-15 |
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CN202111652189.9A Pending CN114349810A (zh) | 2021-12-30 | 2021-12-30 | 甾类化合物通用的手性拆分方法 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116396349A (zh) * | 2023-03-30 | 2023-07-07 | 常德云港生物科技股份有限公司 | 一种异熊去氧胆酸的纯化方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4282161A (en) * | 1979-05-23 | 1981-08-04 | Armand Guillemette | Novel purification process |
CN106928306A (zh) * | 2017-03-15 | 2017-07-07 | 眉山市新功生物科技有限公司 | 一种熊去氧胆酸的纯化方法 |
-
2021
- 2021-12-30 CN CN202111652189.9A patent/CN114349810A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4282161A (en) * | 1979-05-23 | 1981-08-04 | Armand Guillemette | Novel purification process |
CN106928306A (zh) * | 2017-03-15 | 2017-07-07 | 眉山市新功生物科技有限公司 | 一种熊去氧胆酸的纯化方法 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116396349A (zh) * | 2023-03-30 | 2023-07-07 | 常德云港生物科技股份有限公司 | 一种异熊去氧胆酸的纯化方法 |
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CB03 | Change of inventor or designer information |
Inventor after: Zhang Tian Inventor after: Xi Wenxiang Inventor after: Chen Linjian Inventor after: Du Min Inventor after: Li Lei Inventor after: Feng Miao Inventor before: Zhang Tian Inventor before: Xi Wenxiang Inventor before: Chen Linjian Inventor before: Du Min Inventor before: Li Lei |
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CB03 | Change of inventor or designer information | ||
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Application publication date: 20220415 |
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