JPS6232749B2 - - Google Patents
Info
- Publication number
- JPS6232749B2 JPS6232749B2 JP11159082A JP11159082A JPS6232749B2 JP S6232749 B2 JPS6232749 B2 JP S6232749B2 JP 11159082 A JP11159082 A JP 11159082A JP 11159082 A JP11159082 A JP 11159082A JP S6232749 B2 JPS6232749 B2 JP S6232749B2
- Authority
- JP
- Japan
- Prior art keywords
- hydroxycamptothecin
- tetrahydrocamptothecin
- camptothecin
- mmol
- room temperature
- 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
Links
- 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 claims description 33
- HAWSQZCWOQZXHI-FQEVSTJZSA-N 10-Hydroxycamptothecin Chemical compound C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-FQEVSTJZSA-N 0.000 claims description 20
- HAWSQZCWOQZXHI-UHFFFAOYSA-N CPT-OH Natural products C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-UHFFFAOYSA-N 0.000 claims description 20
- 239000000126 substance Substances 0.000 claims description 8
- ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 4
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 4
- 239000012286 potassium permanganate Substances 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 claims description 3
- SOCTUWSJJQCPFX-UHFFFAOYSA-N dichromate(2-) Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O SOCTUWSJJQCPFX-UHFFFAOYSA-N 0.000 claims description 3
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 13
- 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 description 13
- 229940127093 camptothecin Drugs 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- YSAMJAXLRIUOHA-SFVMKZFCSA-N (19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),4,6,8,15(20)-pentaene-14,18-dione Chemical compound N1C2=CC=CC=C2CC(CN2C3=O)C1C2=CC1=C3COC(=O)[C@]1(O)CC YSAMJAXLRIUOHA-SFVMKZFCSA-N 0.000 description 9
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 2
- OQZGYMRYZAKXAF-UHFFFAOYSA-N 2-(4-methylcyclohexyl)acetic acid Chemical compound CC1CCC(CC(O)=O)CC1 OQZGYMRYZAKXAF-UHFFFAOYSA-N 0.000 description 2
- 229910052684 Cerium Inorganic materials 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- GWXLDORMOJMVQZ-UHFFFAOYSA-N cerium Chemical compound [Ce] GWXLDORMOJMVQZ-UHFFFAOYSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- FWFUSMMVFVVERM-UHFFFAOYSA-N 2-(1,4-dioxan-2-yl)acetic acid Chemical compound OC(=O)CC1COCCO1 FWFUSMMVFVVERM-UHFFFAOYSA-N 0.000 description 1
- JHWIEAWILPSRMU-UHFFFAOYSA-N 2-methyl-3-pyrimidin-4-ylpropanoic acid Chemical compound OC(=O)C(C)CC1=CC=NC=N1 JHWIEAWILPSRMU-UHFFFAOYSA-N 0.000 description 1
- 241000759909 Camptotheca Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000007093 Leukemia L1210 Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000209018 Nyssaceae Species 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11159082A JPS595188A (ja) | 1982-06-30 | 1982-06-30 | １０−ヒドロキシカンプトテシンの製造法 |
| BR1100882-2A BR1100882A (pt) | 1982-06-30 | 1997-05-14 | Processo para a preparação de 10-hidroxicamptotecina |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11159082A JPS595188A (ja) | 1982-06-30 | 1982-06-30 | １０−ヒドロキシカンプトテシンの製造法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS595188A JPS595188A (ja) | 1984-01-12 |
| JPS6232749B2 true JPS6232749B2 (ko) | 1987-07-16 |
Family
ID=14565217
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11159082A Granted JPS595188A (ja) | 1982-06-30 | 1982-06-30 | １０−ヒドロキシカンプトテシンの製造法 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS595188A (ko) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0615546B2 (ja) * | 1986-02-24 | 1994-03-02 | 株式会社ヤクルト本社 | 新規なカンプトテシン誘導体 |
| US5053512A (en) * | 1987-04-14 | 1991-10-01 | Research Triangle Institute | Total synthesis of 20(S) and 20(R)-camptothecin and compthothecin derivatives |
| US5106742A (en) * | 1987-03-31 | 1992-04-21 | Wall Monroe E | Camptothecin analogs as potent inhibitors of topoisomerase I |
| US5122526A (en) * | 1987-03-31 | 1992-06-16 | Research Triangle Institute | Camptothecin and analogs thereof and pharmaceutical compositions and method using them |
| US5227380A (en) * | 1987-03-31 | 1993-07-13 | Research Triangle Institute | Pharmaceutical compositions and methods employing camptothecins |
| US5364858A (en) * | 1987-03-31 | 1994-11-15 | Research Triangle Institute | Camptothecin analogs as potent inhibitors of topoisomerase I |
| US4981968A (en) * | 1987-03-31 | 1991-01-01 | Research Triangle Institute | Synthesis of camptothecin and analogs thereof |
| US5049668A (en) * | 1989-09-15 | 1991-09-17 | Research Triangle Institute | 10,11-methylenedioxy-20(RS)-camptothecin analogs |
| US5340817A (en) * | 1987-04-14 | 1994-08-23 | Research Triangle Institute | Method of treating tumors with anti-tumor effective camptothecin compounds |
| US5180722A (en) * | 1987-04-14 | 1993-01-19 | Research Triangle Institute | 10,11-methylenedioxy-20(RS)-camptothecin and 10,11-methylenedioxy-20(S)-camptothecin analogs |
| US5122606A (en) * | 1987-04-14 | 1992-06-16 | Research Triangle Institute | 10,11-methylenedioxy camptothecins |
| US5225404A (en) * | 1989-11-06 | 1993-07-06 | New York University | Methods of treating colon tumors with tumor-inhibiting camptothecin compounds |
| US5552154A (en) * | 1989-11-06 | 1996-09-03 | The Stehlin Foundation For Cancer Research | Method for treating cancer with water-insoluble s-camptothecin of the closed lactone ring form and derivatives thereof |
| JP2848958B2 (ja) * | 1990-09-28 | 1999-01-20 | スミスクライン・ビーチャム・コーポレイション | 水溶性カンプトテシン類似体、方法および手段 |
| US5883255A (en) * | 1990-10-31 | 1999-03-16 | Smithkline Beecham Corporation | Substituted indolizino 1,2-b!quinolinones |
| US6080751A (en) * | 1992-01-14 | 2000-06-27 | The Stehlin Foundation For Cancer Research | Method for treating pancreatic cancer in humans with water-insoluble S-camptothecin of the closed lactone ring form and derivatives thereof |
| US5447936A (en) * | 1993-12-22 | 1995-09-05 | Bionumerik Pharmaceuticals, Inc. | Lactone stable formulation of 10-hydroxy 7-ethyl camptothecin and methods for uses thereof |
| US5468754A (en) * | 1994-04-19 | 1995-11-21 | Bionumerik Pharmaceuticals, Inc. | 11,7 substituted camptothecin derivatives and formulations of 11,7 substituted camptothecin derivatives and methods for uses thereof |
| US5646159A (en) * | 1994-07-20 | 1997-07-08 | Research Triangle Institute | Water-soluble esters of camptothecin compounds |
| US5614529A (en) * | 1994-09-22 | 1997-03-25 | Research Triangle Institute | Inhibition of plasmodia parasites by camptothecin compounds |
| WO1997019085A1 (en) * | 1995-11-22 | 1997-05-29 | Research Triangle Institute | Camptothecin compounds with combined topoisomerase i inhibition and dna alkylation properties |
| CZ298259B6 (cs) | 2000-02-28 | 2007-08-08 | Aventis Pharma S. A. | Farmaceutická kombinace k lécení rakoviny obsahující CPT-11 a capecitabin |
| US6545010B2 (en) | 2000-03-17 | 2003-04-08 | Aventis Pharma S.A. | Composition comprising camptothecin or a camptothecin derivative and a platin derivative for the treatment of cancer |
| US6486320B2 (en) | 2000-09-15 | 2002-11-26 | Aventis Pharma S.A. | Preparation of camptothecin and of its derivatives |
| JP2004517821A (ja) | 2000-10-27 | 2004-06-17 | アベンティス・ファーマ・ソシエテ・アノニム | 癌治療のためのカンプトセシン及びスチルベン誘導体からなる組合せ |
| WO2004055020A1 (en) * | 2002-12-16 | 2004-07-01 | Council Of Scientific And Industrial Research | Process for the direct preparation of 5-alkoxy and 5-acyloxy analogues of campthothecins or mappicene ketones |
| CA2523059A1 (en) | 2003-05-12 | 2004-11-25 | Scinopharm Taiwan, Ltd. | Process for the preparation of 7-alkyl-10-hydroxy-20(s)-camptothecin |
| CZ298934B6 (cs) * | 2003-08-26 | 2008-03-12 | Pliva- Lachema A.S. | Zpusob výroby 7-ethyl-10-hydroxykamptothecinu |
| CZ299593B6 (cs) * | 2003-12-16 | 2008-09-10 | Pliva-Lachema A. S. | Zpusob výroby 7-ethyl-10-hydroxykamptothecinu |
| US20050272757A1 (en) * | 2004-06-04 | 2005-12-08 | Phytogen Life Sciences Inc. | Process to prepare camptothecin derivatives and novel intermediate and compounds thereof |
| ES2425621T3 (es) | 2008-05-29 | 2013-10-16 | Microbiopharm Japan Co., Ltd. | Métodos para producir derivados de camptotecina |
-
1982
- 1982-06-30 JP JP11159082A patent/JPS595188A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS595188A (ja) | 1984-01-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPS6232749B2 (ko) | ||
| White et al. | Synthetic studies of the pyrroloquinoline nucleus of the makaluvamine alkaloids. Synthesis of the topoisomerase II inhibitor makaluvamine D | |
| JP5824448B2 (ja) | モルフィナンおよびモルフィノン化合物の調製法 | |
| CA2173671A1 (en) | Condensed-hexacyclic compounds and a process therefor | |
| WO1993008189A1 (en) | Chemical reactions on camptothecin or analogs | |
| JPH0310630B2 (ko) | ||
| JPH0312070B2 (ko) | ||
| CN110330500B (zh) | 一种6β-羟基-7,8-二氢-吗啡衍生物的立体选择性合成方法 | |
| US20230257392A1 (en) | Intermediate for synthesizing camptothecin derivative, preparation method therefor, and use thereof | |
| JP3842278B2 (ja) | ９−ニトロ−２０−カンプトセシン（９−ｎｉｔｒｏ−２０−ｃａｍｐｔｏｔｈｅｃｉｎ）の調製および精製方法 | |
| JPS6150985A (ja) | 新規なカンプトテシン誘導体 | |
| CA2569266A1 (en) | Process to prepare camptothecin derivatives and novel intermediate and compounds thereof | |
| JPH029032B2 (ko) | ||
| JPS6247193B2 (ko) | ||
| EP2705040A1 (en) | Process for the preparation of morphine analogs via metal catalyzed n-demethylation/functionalization and intramolecular group transfer | |
| JPS6247873B2 (ko) | ||
| JP5270091B2 (ja) | ７−アルキル−１０−ヒドロキシ−２０（ｓ）−カンプトテシンを調製するためのプロセス | |
| JPS6247190B2 (ko) | ||
| JP2002517399A (ja) | 新規なビンカアルカロイド誘導体及びその調製方法 | |
| JPS6247194B2 (ko) | ||
| RU2145325C1 (ru) | Способы получения 9-аминокамптотецина, промежуточные продукты и способ их получения | |
| JPS636070B2 (ko) | ||
| JPS645034B2 (ko) | ||
| CN100475811C (zh) | 地舍平的半合成方法 | |
| JPS636072B2 (ko) |