JPS61227796A - 光学活性インドリン−２−カルボン酸の製造方法 - Google Patents
光学活性インドリン−２−カルボン酸の製造方法Info
- Publication number
- JPS61227796A JPS61227796A JP6976985A JP6976985A JPS61227796A JP S61227796 A JPS61227796 A JP S61227796A JP 6976985 A JP6976985 A JP 6976985A JP 6976985 A JP6976985 A JP 6976985A JP S61227796 A JPS61227796 A JP S61227796A
- Authority
- JP
- Japan
- Prior art keywords
- carboxylic acid
- indoline
- optically active
- microorganism
- enzyme
- 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.)
- Granted
Links
- QNRXNRGSOJZINA-UHFFFAOYSA-N indoline-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)CC2=C1 QNRXNRGSOJZINA-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 238000004519 manufacturing process Methods 0.000 title claims description 21
- 108090000790 Enzymes Proteins 0.000 claims abstract description 30
- 102000004190 Enzymes Human genes 0.000 claims abstract description 30
- 244000005700 microbiome Species 0.000 claims abstract description 29
- 150000001875 compounds Chemical class 0.000 claims abstract description 12
- 108090000371 Esterases Proteins 0.000 claims abstract description 8
- 230000000694 effects Effects 0.000 claims abstract description 8
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 8
- 230000000707 stereoselective effect Effects 0.000 claims abstract description 7
- 125000005843 halogen group Chemical group 0.000 claims abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
- 125000002723 alicyclic group Chemical group 0.000 claims abstract description 5
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
- 239000000126 substance Substances 0.000 claims description 14
- 230000003287 optical effect Effects 0.000 claims description 12
- 241000228212 Aspergillus Species 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 6
- 241000589516 Pseudomonas Species 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 238000000926 separation method Methods 0.000 claims description 5
- 241000187747 Streptomyces Species 0.000 claims description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 2
- QNRXNRGSOJZINA-QMMMGPOBSA-N (2s)-2,3-dihydro-1h-indole-2-carboxylic acid Chemical compound C1=CC=C2N[C@H](C(=O)O)CC2=C1 QNRXNRGSOJZINA-QMMMGPOBSA-N 0.000 claims 4
- QNRXNRGSOJZINA-MRVPVSSYSA-N (2r)-2,3-dihydro-1h-indole-2-carboxylic acid Chemical compound C1=CC=C2N[C@@H](C(=O)O)CC2=C1 QNRXNRGSOJZINA-MRVPVSSYSA-N 0.000 claims 3
- 239000013543 active substance Substances 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 210000000056 organ Anatomy 0.000 claims 2
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 15
- 150000002148 esters Chemical class 0.000 abstract description 9
- 230000007062 hydrolysis Effects 0.000 abstract description 8
- 239000000203 mixture Substances 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 230000001580 bacterial effect Effects 0.000 description 10
- 239000000758 substrate Substances 0.000 description 10
- 238000000605 extraction Methods 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 5
- 230000000813 microbial effect Effects 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 244000063299 Bacillus subtilis Species 0.000 description 4
- 235000014469 Bacillus subtilis Nutrition 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 108090001060 Lipase Proteins 0.000 description 4
- 239000004367 Lipase Substances 0.000 description 4
- 102000004882 Lipase Human genes 0.000 description 4
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- -1 ethylene glycol ester Chemical class 0.000 description 4
- 235000019421 lipase Nutrition 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 241000187392 Streptomyces griseus Species 0.000 description 3
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000004254 Ammonium phosphate Substances 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000001888 Peptone Substances 0.000 description 2
- 108010080698 Peptones Proteins 0.000 description 2
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 2
- 235000019289 ammonium phosphates Nutrition 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 235000013372 meat Nutrition 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 235000019319 peptone Nutrition 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 108091016642 steapsin Proteins 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- BWLBGMIXKSTLSX-UHFFFAOYSA-N 2-hydroxyisobutyric acid Chemical compound CC(C)(O)C(O)=O BWLBGMIXKSTLSX-UHFFFAOYSA-N 0.000 description 1
- SSZWWUDQMAHNAQ-UHFFFAOYSA-N 3-chloropropane-1,2-diol Chemical compound OCC(O)CCl SSZWWUDQMAHNAQ-UHFFFAOYSA-N 0.000 description 1
- 101800000734 Angiotensin-1 Proteins 0.000 description 1
- 102400000344 Angiotensin-1 Human genes 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 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
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000013028 medium composition Substances 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical class [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 239000002994 raw material Substances 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
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Indole Compounds (AREA)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6976985A JPS61227796A (ja) | 1985-04-01 | 1985-04-01 | 光学活性インドリン−２−カルボン酸の製造方法 |
| DE8686104352T DE3680132D1 (de) | 1985-04-01 | 1986-03-29 | Verfahren zur herstellung von optisch aktiver indolin-2-carbonsaeure. |
| EP86104352A EP0197474B1 (en) | 1985-04-01 | 1986-03-29 | Process for preparing optically active indoline-2-carboxylic acid |
| US06/846,436 US4898822A (en) | 1985-04-01 | 1986-03-31 | Process for preparing optically active indoline-2-carboxylic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6976985A JPS61227796A (ja) | 1985-04-01 | 1985-04-01 | 光学活性インドリン−２−カルボン酸の製造方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61227796A true JPS61227796A (ja) | 1986-10-09 |
| JPH0573396B2 JPH0573396B2 (enrdf_load_stackoverflow) | 1993-10-14 |
Family
ID=13412332
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6976985A Granted JPS61227796A (ja) | 1985-04-01 | 1985-04-01 | 光学活性インドリン−２−カルボン酸の製造方法 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61227796A (enrdf_load_stackoverflow) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61282093A (ja) * | 1985-06-08 | 1986-12-12 | Kanegafuchi Chem Ind Co Ltd | 固定化酵素もしくは固定化微生物による光学活性インドリン−２−カルボン酸の製造方法 |
| KR100377289B1 (ko) * | 1995-09-06 | 2003-08-09 | 씨제이 주식회사 | 신규피리돈카르복실산유도체의중간체합성에관한새로운광학분할방법 |
| JP2005151976A (ja) * | 2003-10-30 | 2005-06-16 | Sumitomo Chemical Co Ltd | 光学活性なｎ−保護−オクタヒドロ−１ｈ−インドール−２−カルボン酸の製造方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5781460A (en) * | 1980-11-10 | 1982-05-21 | Mochida Pharmaceut Co Ltd | Novel indolinecarboxylic acid derivative |
-
1985
- 1985-04-01 JP JP6976985A patent/JPS61227796A/ja active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5781460A (en) * | 1980-11-10 | 1982-05-21 | Mochida Pharmaceut Co Ltd | Novel indolinecarboxylic acid derivative |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61282093A (ja) * | 1985-06-08 | 1986-12-12 | Kanegafuchi Chem Ind Co Ltd | 固定化酵素もしくは固定化微生物による光学活性インドリン−２−カルボン酸の製造方法 |
| KR100377289B1 (ko) * | 1995-09-06 | 2003-08-09 | 씨제이 주식회사 | 신규피리돈카르복실산유도체의중간체합성에관한새로운광학분할방법 |
| JP2005151976A (ja) * | 2003-10-30 | 2005-06-16 | Sumitomo Chemical Co Ltd | 光学活性なｎ−保護−オクタヒドロ−１ｈ−インドール−２−カルボン酸の製造方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0573396B2 (enrdf_load_stackoverflow) | 1993-10-14 |
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