CA2203844C - Procede d'isolement du paclitaxel et de la 9-dihydro-13-acetylbaccatine iii - Google Patents
Procede d'isolement du paclitaxel et de la 9-dihydro-13-acetylbaccatine iii Download PDFInfo
- Publication number
- CA2203844C CA2203844C CA 2203844 CA2203844A CA2203844C CA 2203844 C CA2203844 C CA 2203844C CA 2203844 CA2203844 CA 2203844 CA 2203844 A CA2203844 A CA 2203844A CA 2203844 C CA2203844 C CA 2203844C
- Authority
- CA
- Canada
- Prior art keywords
- taxane
- column
- methanol
- chloroform
- ratio
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 55
- WPPPFZJNKLMYBW-FAEUQDRCSA-N 13-acetyl-9-dihydrobaccatin iii Chemical compound O([C@@H]1[C@]2(O)C[C@@H](C(=C([C@@H](OC(C)=O)[C@H](O)[C@]3(C)[C@@H](O)C[C@H]4OC[C@]4([C@H]31)OC(C)=O)C2(C)C)C)OC(=O)C)C(=O)C1=CC=CC=C1 WPPPFZJNKLMYBW-FAEUQDRCSA-N 0.000 title claims abstract description 21
- FFCWRLFQIKDRNO-UHFFFAOYSA-N 9-dihydro-13-acetyl baccatin III Natural products CC(=O)OC1C2C(O)CC(OC(=O)C)C3(CO3)C2C(OC(=O)C)C4(O)CC(OC(=O)C)C(=C(C1OC(=O)C)C4(C)C)C FFCWRLFQIKDRNO-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 229930012538 Paclitaxel Natural products 0.000 title claims abstract description 15
- 229960001592 paclitaxel Drugs 0.000 title claims abstract description 15
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 title claims abstract description 15
- 230000008569 process Effects 0.000 title description 8
- 238000002955 isolation Methods 0.000 title description 6
- 229940123237 Taxane Drugs 0.000 claims abstract description 62
- 238000004440 column chromatography Methods 0.000 claims abstract description 22
- 241001116500 Taxus Species 0.000 claims abstract description 15
- 239000000284 extract Substances 0.000 claims abstract description 14
- 239000000287 crude extract Substances 0.000 claims abstract description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 141
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 63
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 58
- 239000002904 solvent Substances 0.000 claims description 47
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 46
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 claims description 45
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 42
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 34
- 239000000741 silica gel Substances 0.000 claims description 34
- 229910002027 silica gel Inorganic materials 0.000 claims description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- 238000004587 chromatography analysis Methods 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 19
- 239000013078 crystal Substances 0.000 claims description 15
- 239000004677 Nylon Substances 0.000 claims description 10
- 229920001778 nylon Polymers 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 8
- 239000012141 concentrate Substances 0.000 claims description 8
- 241000015728 Taxus canadensis Species 0.000 claims description 7
- 230000001476 alcoholic effect Effects 0.000 claims description 7
- 239000004005 microsphere Substances 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000000605 extraction Methods 0.000 claims description 5
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 claims description 4
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 claims description 4
- 239000003208 petroleum Substances 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 3
- 230000008901 benefit Effects 0.000 abstract description 5
- 239000000243 solution Substances 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 238000000926 separation method Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 8
- 241000196324 Embryophyta Species 0.000 description 7
- 238000011161 development Methods 0.000 description 6
- 239000002798 polar solvent Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 101150041968 CDC13 gene Proteins 0.000 description 4
- 102000029749 Microtubule Human genes 0.000 description 4
- 108091022875 Microtubule Proteins 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 210000004688 microtubule Anatomy 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 239000003463 adsorbent Substances 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000011210 chromatographic step Methods 0.000 description 3
- 238000011031 large-scale manufacturing process Methods 0.000 description 3
- 239000011877 solvent mixture Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 239000002250 absorbent Substances 0.000 description 2
- 230000002745 absorbent Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 239000012454 non-polar solvent Substances 0.000 description 2
- 230000002250 progressing effect Effects 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 101100536354 Drosophila melanogaster tant gene Proteins 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 229930010859 axane Natural products 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000004185 countercurrent chromatography Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- 229930004069 diterpene Natural products 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000011491 glass wool Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000000401 methanolic extract Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000000039 preparative column chromatography Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- -1 taxane diterpene Chemical class 0.000 description 1
- 230000029305 taxis Effects 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Epoxy Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2203844 CA2203844C (fr) | 1997-04-28 | 1997-04-28 | Procede d'isolement du paclitaxel et de la 9-dihydro-13-acetylbaccatine iii |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2203844 CA2203844C (fr) | 1997-04-28 | 1997-04-28 | Procede d'isolement du paclitaxel et de la 9-dihydro-13-acetylbaccatine iii |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2203844A1 CA2203844A1 (fr) | 1998-10-28 |
| CA2203844C true CA2203844C (fr) | 2004-01-27 |
Family
ID=29274791
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2203844 Expired - Fee Related CA2203844C (fr) | 1997-04-28 | 1997-04-28 | Procede d'isolement du paclitaxel et de la 9-dihydro-13-acetylbaccatine iii |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2203844C (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103588736B (zh) * | 2013-12-03 | 2015-06-03 | 云南汉德生物技术有限公司 | 13-乙酰基-9-羟基巴卡亭iii的提取分离方法 |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6229027B1 (en) * | 2000-03-10 | 2001-05-08 | Jian Liu | Process for manufacturing paclitaxel and 13-acetyl-9-dihydrobaccatin IV |
| AU2006201733B2 (en) * | 2000-03-10 | 2007-05-24 | Ivax Research, Inc. | Process for manufacturing paclitaxel and 13-acetyl-9-dihydrobaccatin III |
| WO2002038555A1 (fr) | 2000-11-13 | 2002-05-16 | Lahu Saiji | Procede pour isoler des taxanes |
| CN1328269C (zh) * | 2004-03-18 | 2007-07-25 | 中国科学院大连化学物理研究所 | 一种紫杉醇的制备方法 |
-
1997
- 1997-04-28 CA CA 2203844 patent/CA2203844C/fr not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103588736B (zh) * | 2013-12-03 | 2015-06-03 | 云南汉德生物技术有限公司 | 13-乙酰基-9-羟基巴卡亭iii的提取分离方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2203844A1 (fr) | 1998-10-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5969165A (en) | Isolation and purification of paclitaxel and other related taxanes by industrial preparative low pressure chromatography on a polymeric resin column | |
| US5279949A (en) | Process for the isolation and purification of taxol and taxanes from Taxus spp | |
| AU760242B2 (en) | Method for high yield extraction of paclitaxel from paclitaxel-containing material | |
| CA2203844C (fr) | Procede d'isolement du paclitaxel et de la 9-dihydro-13-acetylbaccatine iii | |
| US6229027B1 (en) | Process for manufacturing paclitaxel and 13-acetyl-9-dihydrobaccatin IV | |
| US20030013899A1 (en) | Production of taxol and taxanes | |
| RU2276669C2 (ru) | Способ хроматографического разделения паклитаксела и цефаломаннина | |
| US6878832B2 (en) | Isolation of taxanes | |
| AU2006201733B2 (en) | Process for manufacturing paclitaxel and 13-acetyl-9-dihydrobaccatin III | |
| CA2258066C (fr) | Separation et purification de paclitaxel et d'autres taxanes voisines par chromatographie industrielle de preparation a faible pression sur une colonne en resine polymere | |
| RU2373198C2 (ru) | СПОСОБЫ ПОЛУЧЕНИЯ ПАКЛИТАКСЕЛА ИЗ РАСТЕНИЙ РОДА Taxus | |
| SU1146050A1 (ru) | Способ получени @ -экдизона из растени рода @ | |
| UA68355C2 (en) | Method for isolating and purifying taxan analogues, in particular paclitaxel (variants) | |
| MXPA00000318A (en) | Isolation and purification of paclitaxel and other related taxanes by industrial preparative low pressure chromatography on a polymeric resin column | |
| US6215000B1 (en) | Crystalline complexes of baccatin III with imidazole, 2-methylimidazole or isopropanol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |