JPS63146895A - 二水和タウロウルソデオキシコール酸の合成方法 - Google Patents
二水和タウロウルソデオキシコール酸の合成方法Info
- Publication number
- JPS63146895A JPS63146895A JP62248219A JP24821987A JPS63146895A JP S63146895 A JPS63146895 A JP S63146895A JP 62248219 A JP62248219 A JP 62248219A JP 24821987 A JP24821987 A JP 24821987A JP S63146895 A JPS63146895 A JP S63146895A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- solution
- taurine
- solvent
- salt
- Prior art date
- 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
Links
- 239000002253 acid Substances 0.000 title claims description 20
- 230000015572 biosynthetic process Effects 0.000 title description 3
- 238000003786 synthesis reaction Methods 0.000 title description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims description 26
- 150000008064 anhydrides Chemical class 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 19
- 239000000243 solution Substances 0.000 claims description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 15
- 229960003080 taurine Drugs 0.000 claims description 13
- -1 alkyl chloroformate Chemical compound 0.000 claims description 11
- 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 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 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 claims description 6
- 229960001661 ursodiol Drugs 0.000 claims description 6
- BHTRKEVKTKCXOH-UHFFFAOYSA-N Taurochenodesoxycholsaeure Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)CC2 BHTRKEVKTKCXOH-UHFFFAOYSA-N 0.000 claims description 5
- BHTRKEVKTKCXOH-LBSADWJPSA-N tauroursodeoxycholic 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)NCCS(O)(=O)=O)C)[C@@]2(C)CC1 BHTRKEVKTKCXOH-LBSADWJPSA-N 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical group CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 239000006188 syrup Substances 0.000 claims description 4
- 235000020357 syrup Nutrition 0.000 claims description 4
- 150000003512 tertiary amines Chemical class 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 3
- LPCWDBCEHWHJGX-UHFFFAOYSA-N 1-ethyl-2-methylpiperidine Chemical group CCN1CCCCC1C LPCWDBCEHWHJGX-UHFFFAOYSA-N 0.000 claims description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 2
- 229910001854 alkali hydroxide Inorganic materials 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 150000001447 alkali salts Chemical class 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 239000012442 inert solvent Substances 0.000 claims description 2
- 159000000000 sodium salts Chemical class 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 claims 1
- 239000003021 water soluble solvent Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 210000001557 animal structure Anatomy 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 208000017283 Bile Duct disease Diseases 0.000 description 1
- 239000002879 Lewis base Substances 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 150000004683 dihydrates Chemical group 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000007323 disproportionation reaction Methods 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- NBEMQPLNBYYUAZ-UHFFFAOYSA-N ethyl acetate;propan-2-one Chemical compound CC(C)=O.CCOC(C)=O NBEMQPLNBYYUAZ-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000007527 lewis bases Chemical class 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
- C07J41/0061—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives one of the carbon atoms being part of an amide group
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT21892A/86 | 1986-10-03 | ||
| IT21892/86A IT1197330B (it) | 1986-10-03 | 1986-10-03 | Procedimento per la sintesi di acido tauroursodesossicolico biidrato |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63146895A true JPS63146895A (ja) | 1988-06-18 |
Family
ID=11188314
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62248219A Pending JPS63146895A (ja) | 1986-10-03 | 1987-10-02 | 二水和タウロウルソデオキシコール酸の合成方法 |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPS63146895A (it) |
| DE (1) | DE3736918A1 (it) |
| IT (1) | IT1197330B (it) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0327396A (ja) * | 1989-06-23 | 1991-02-05 | Tokyo Tanabe Co Ltd | タウロウルソデオキシコール酸ナトリウムの製造方法 |
| JPH04169597A (ja) * | 1990-10-31 | 1992-06-17 | Tokyo Tanabe Co Ltd | タウリン抱合型胆汁酸の精製方法 |
| EP0793967A3 (en) * | 1996-03-04 | 1999-02-03 | Prodotti Chimici E Alimentari Spa | Conjugated compounds of bile acids with thiotaurine and its N-alkyl derivatives |
| JP2010525003A (ja) * | 2007-04-23 | 2010-07-22 | プロドッティ キミチ エ アリメンタリ ソシエタ ペル アチオニ | タウロウルソデオキシコール酸の調製のための方法 |
| CN105294809A (zh) * | 2015-12-21 | 2016-02-03 | 杭州和泽医药科技有限公司 | 一种牛磺熊去氧胆酸的制备方法 |
| CN105330715A (zh) * | 2016-01-04 | 2016-02-17 | 杭州和泽医药科技有限公司 | 一种牛磺熊去氧胆酸的制备方法 |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5260462A (en) * | 1989-05-30 | 1993-11-09 | Prodotti Chimici E Alimentari S.P.A. | Purification of tauroursodesoxycholic acid dihydrate |
| IT1270853B (it) * | 1993-05-20 | 1997-05-13 | Sanofi Elf | Procedimento per la preparazione di derivati taurocolanici |
| WO2010005594A1 (en) * | 2008-07-10 | 2010-01-14 | Regenemed Inc. | Compositions and methods of producing ursodeoxycholic acid |
| IT201900005906A1 (it) | 2019-04-16 | 2020-10-16 | Dipharma Francis Srl | Procedimento di preparazione di coniugati di un acido colanico |
-
1986
- 1986-10-03 IT IT21892/86A patent/IT1197330B/it active Protection Beyond IP Right Term
-
1987
- 1987-10-02 JP JP62248219A patent/JPS63146895A/ja active Pending
- 1987-10-30 DE DE19873736918 patent/DE3736918A1/de not_active Withdrawn
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0327396A (ja) * | 1989-06-23 | 1991-02-05 | Tokyo Tanabe Co Ltd | タウロウルソデオキシコール酸ナトリウムの製造方法 |
| JPH04169597A (ja) * | 1990-10-31 | 1992-06-17 | Tokyo Tanabe Co Ltd | タウリン抱合型胆汁酸の精製方法 |
| EP0793967A3 (en) * | 1996-03-04 | 1999-02-03 | Prodotti Chimici E Alimentari Spa | Conjugated compounds of bile acids with thiotaurine and its N-alkyl derivatives |
| JP2010525003A (ja) * | 2007-04-23 | 2010-07-22 | プロドッティ キミチ エ アリメンタリ ソシエタ ペル アチオニ | タウロウルソデオキシコール酸の調製のための方法 |
| KR101522740B1 (ko) * | 2007-04-23 | 2015-05-26 | 프로도티 케미시 에 엘리멘타리 에스.피.에이. | 타우로우르소데옥시콜린산 제조 공정 |
| CN105294809A (zh) * | 2015-12-21 | 2016-02-03 | 杭州和泽医药科技有限公司 | 一种牛磺熊去氧胆酸的制备方法 |
| CN105330715A (zh) * | 2016-01-04 | 2016-02-17 | 杭州和泽医药科技有限公司 | 一种牛磺熊去氧胆酸的制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| IT8621892A1 (it) | 1988-04-03 |
| IT8621892A0 (it) | 1986-10-03 |
| DE3736918A1 (de) | 1989-05-11 |
| IT1197330B (it) | 1988-11-30 |
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