CN1096297A - 合成喜树碱和麦皮星以及它们的类似物和有关化合物的方法 - Google Patents
合成喜树碱和麦皮星以及它们的类似物和有关化合物的方法 Download PDFInfo
- Publication number
- CN1096297A CN1096297A CN93119287A CN93119287A CN1096297A CN 1096297 A CN1096297 A CN 1096297A CN 93119287 A CN93119287 A CN 93119287A CN 93119287 A CN93119287 A CN 93119287A CN 1096297 A CN1096297 A CN 1096297A
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- Prior art keywords
- quinoline
- indolizino
- ketone
- ester
- group
- 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
- 238000000034 method Methods 0.000 title claims abstract description 89
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 title claims abstract description 79
- 150000001875 compounds Chemical class 0.000 title claims abstract description 71
- QHTFEANXLNNBOX-UHFFFAOYSA-N 8-methyl-7-propanoyl-11h-indolizino[1,2-b]quinolin-9-one Chemical compound C1=CC=C2C=C(CN3C4=CC(=C(C3=O)C)C(=O)CC)C4=NC2=C1 QHTFEANXLNNBOX-UHFFFAOYSA-N 0.000 claims abstract description 26
- WAZSVCKLDOMJJX-UHFFFAOYSA-N 2h-pyrrolo[3,4-b]quinoline Chemical compound C1=CC=CC2=CC3=CNC=C3N=C21 WAZSVCKLDOMJJX-UHFFFAOYSA-N 0.000 claims abstract description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 63
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 54
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 52
- -1 cyclic lactone Chemical class 0.000 claims description 43
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 34
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 22
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 20
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- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 19
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- HCPOCMMGKBZWSJ-UHFFFAOYSA-N ethyl 3-hydrazinyl-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NN HCPOCMMGKBZWSJ-UHFFFAOYSA-N 0.000 claims description 13
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- 238000010992 reflux Methods 0.000 claims description 8
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- 238000006297 dehydration reaction Methods 0.000 claims description 6
- VDDXQSUSMHZCLS-UHFFFAOYSA-N ethenyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC=C VDDXQSUSMHZCLS-UHFFFAOYSA-N 0.000 claims description 6
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- 229910052740 iodine Inorganic materials 0.000 claims description 6
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- MWFNDFNHIBULHZ-UHFFFAOYSA-N oxoaluminum;hydrochloride Chemical compound Cl.[Al]=O MWFNDFNHIBULHZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 5
- IEEHKTFVUIVORU-UHFFFAOYSA-N 2-methylpropanedioyl dichloride Chemical compound ClC(=O)C(C)C(Cl)=O IEEHKTFVUIVORU-UHFFFAOYSA-N 0.000 claims description 4
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- SXYFKXOFMCIXQW-UHFFFAOYSA-N propanedioyl dichloride Chemical compound ClC(=O)CC(Cl)=O SXYFKXOFMCIXQW-UHFFFAOYSA-N 0.000 claims description 4
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- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 3
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- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
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- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000006242 amine protecting group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
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- 125000003118 aryl group Chemical group 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000013475 authorization Methods 0.000 description 1
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- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
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- 238000010790 dilution Methods 0.000 description 1
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- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
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- 201000004101 esophageal cancer Diseases 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
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000000295 fuel oil Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000003808 methanol extraction Methods 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 230000000174 oncolytic effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- HWLDNSXPUQTBOD-UHFFFAOYSA-N platinum-iridium alloy Chemical compound [Ir].[Pt] HWLDNSXPUQTBOD-UHFFFAOYSA-N 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 238000010916 retrosynthetic analysis Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- FBTUMDXHSRTGRV-ALTNURHMSA-N zorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(\C)=N\NC(=O)C=1C=CC=CC=1)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 FBTUMDXHSRTGRV-ALTNURHMSA-N 0.000 description 1
- 229960000641 zorubicin Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/14—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94149692A | 1992-09-08 | 1992-09-08 | |
| US941,496 | 1992-09-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1096297A true CN1096297A (zh) | 1994-12-14 |
Family
ID=25476581
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN93119287A Pending CN1096297A (zh) | 1992-09-08 | 1993-09-08 | 合成喜树碱和麦皮星以及它们的类似物和有关化合物的方法 |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0660835A4 (https=) |
| JP (1) | JPH08501104A (https=) |
| KR (1) | KR950702987A (https=) |
| CN (1) | CN1096297A (https=) |
| AU (2) | AU5102393A (https=) |
| CA (1) | CA2144048A1 (https=) |
| MX (1) | MX9305517A (https=) |
| NZ (1) | NZ255942A (https=) |
| TW (1) | TW246674B (https=) |
| WO (1) | WO1994005672A1 (https=) |
| ZA (1) | ZA936580B (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105859716A (zh) * | 2016-05-06 | 2016-08-17 | 华东师范大学 | 一种合成喜树碱类化合物中5-6并环结构的方法 |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6660861B1 (en) * | 2003-03-27 | 2003-12-09 | Council Of Scientific And Industrial Research | Process for preparing Topotecan from 10-hydroxy-4-(S) camptothecin |
| CN2757510Y (zh) | 2004-12-06 | 2006-02-08 | 鸿富锦精密工业（深圳）有限公司 | 散热器扣具 |
| US7520313B2 (en) | 2006-03-16 | 2009-04-21 | Fu Zhun Precision Industry (Shen Zhen) Co., Ltd. | Locking device for heat sink |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5626677B2 (https=) * | 1973-03-26 | 1981-06-19 | ||
| JPS5217499A (en) * | 1975-07-31 | 1977-02-09 | Nippon Chemiphar Co Ltd | Preparation of mappicine |
| DE2534601C2 (de) * | 1975-08-02 | 1987-01-22 | Basf Ag, 6700 Ludwigshafen | Verfahren zur Herstellung von Camptothecin und Camptothecin-Derivaten |
| CA1332413C (en) * | 1987-06-25 | 1994-10-11 | Kabushiki Kaisha Yakult Honsha | Camptothecin derivatives and process for preparing same |
| JP2711728B2 (ja) * | 1989-08-29 | 1998-02-10 | 株式会社ヤクルト本社 | 新規キノリン誘導体およびその製造法 |
| US5155225A (en) * | 1990-09-28 | 1992-10-13 | Smithkline Beecham Corporation | Method for making certain pyrano[3',4':6,7]indolizino-[1,2-B]quinolinones |
-
1993
- 1993-09-07 ZA ZA936580A patent/ZA936580B/xx unknown
- 1993-09-08 AU AU51023/93A patent/AU5102393A/en not_active Abandoned
- 1993-09-08 NZ NZ255942A patent/NZ255942A/en unknown
- 1993-09-08 KR KR1019950700883A patent/KR950702987A/ko not_active Withdrawn
- 1993-09-08 JP JP6507518A patent/JPH08501104A/ja active Pending
- 1993-09-08 WO PCT/US1993/008434 patent/WO1994005672A1/en not_active Ceased
- 1993-09-08 CN CN93119287A patent/CN1096297A/zh active Pending
- 1993-09-08 EP EP93920496A patent/EP0660835A4/en not_active Withdrawn
- 1993-09-08 CA CA002144048A patent/CA2144048A1/en not_active Abandoned
- 1993-09-08 MX MX9305517A patent/MX9305517A/es unknown
- 1993-11-02 TW TW082109133A patent/TW246674B/zh active
-
1997
- 1997-07-11 AU AU28591/97A patent/AU2859197A/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105859716A (zh) * | 2016-05-06 | 2016-08-17 | 华东师范大学 | 一种合成喜树碱类化合物中5-6并环结构的方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1994005672A1 (en) | 1994-03-17 |
| AU5102393A (en) | 1994-03-29 |
| ZA936580B (en) | 1994-08-01 |
| NZ255942A (en) | 1996-11-26 |
| KR950702987A (ko) | 1995-08-23 |
| CA2144048A1 (en) | 1994-03-17 |
| AU2859197A (en) | 1997-10-23 |
| JPH08501104A (ja) | 1996-02-06 |
| EP0660835A4 (en) | 1995-08-16 |
| MX9305517A (es) | 1994-05-31 |
| TW246674B (https=) | 1995-05-01 |
| EP0660835A1 (en) | 1995-07-05 |
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