JPS6232749B2 - - Google Patents

Info

Publication number: JPS6232749B2
Authority: JP; Japan
Prior art keywords: hydroxycamptothecin; tetrahydrocamptothecin; camptothecin; mmol; room temperature
Prior art date: 1982-06-30
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

Application number

JP11159082A

Other languages

English (en)

Japanese (ja)

Other versions

JPS595188A (ja

Inventor

Sada Myasaka

Seigo Sawada

Kenichiro Nogata

Masahiko Mutai

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Yakult Honsha Co Ltd

Original Assignee

Yakult Honsha Co Ltd

Priority date (The priority date 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 date listed.)

1982-06-30

Filing date

1982-06-30

Publication date

1987-07-16

1982-06-30 Application filed by Yakult Honsha Co Ltd filed Critical Yakult Honsha Co Ltd

1982-06-30 Priority to JP11159082A priority Critical patent/JPS595188A/ja

1984-01-12 Publication of JPS595188A publication Critical patent/JPS595188A/ja

1987-07-16 Publication of JPS6232749B2 publication Critical patent/JPS6232749B2/ja

1997-05-14 Priority to BR1100882-2A priority patent/BR1100882A/pt

Status Granted legal-status Critical Current

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)

JP11159082A 1982-06-30 1982-06-30 １０−ヒドロキシカンプトテシンの製造法 Granted JPS595188A (ja)

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 (de)	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 (de)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
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
US5122526A (en) *	1987-03-31	1992-06-16	Research Triangle Institute	Camptothecin and analogs thereof and pharmaceutical compositions and method using them
US4981968A (en) *	1987-03-31	1991-01-01	Research Triangle Institute	Synthesis of camptothecin and analogs thereof
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
US5106742A (en) *	1987-03-31	1992-04-21	Wall Monroe E	Camptothecin analogs as potent inhibitors of topoisomerase I
US5053512A (en) *	1987-04-14	1991-10-01	Research Triangle Institute	Total synthesis of 20(S) and 20(R)-camptothecin and compthothecin derivatives
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
US5122606A (en) *	1987-04-14	1992-06-16	Research Triangle Institute	10,11-methylenedioxy camptothecins
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
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
US5225404A (en) *	1989-11-06	1993-07-06	New York University	Methods of treating colon tumors with tumor-inhibiting camptothecin compounds
CZ51593A3 (en) *	1990-09-28	1994-01-19	Smithkline Beecham Corp	Water-soluble analogs of camptothecine, process of their preparation and use
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
ATE344670T1 (de)	2000-02-28	2006-11-15	Pfizer Entpr Sarl	Synergistische kombination zur behandlung von kolorektalkarzinom
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
AU1602902A (en)	2000-10-27	2002-05-06	Aventis Pharma Sa	A combination comprising camptothecin and a stilbene derivative for the treatment of cancer
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
AU2004238358B2 (en)	2003-05-12	2010-05-13	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
AU2009252303B2 (en)	2008-05-29	2013-04-04	Microbiopharm Japan Co., Ltd.	Production method for camptothecin derivative

1982
- 1982-06-30 JP JP11159082A patent/JPS595188A/ja active Granted

Also Published As

Publication number	Publication date
JPS595188A (ja)	1984-01-12

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White et al.	1994	Synthetic studies of the pyrroloquinoline nucleus of the makaluvamine alkaloids. Synthesis of the topoisomerase II inhibitor makaluvamine D
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WO1993008189A1 (en)	1993-04-29	Chemical reactions on camptothecin or analogs
JPH0310630B2 (de)	1991-02-14
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CA2569266A1 (en)	2005-12-15	Process to prepare camptothecin derivatives and novel intermediate and compounds thereof
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