JPH029032B2 - - Google Patents

Info

Publication number: JPH029032B2
Authority: JP; Japan
Prior art keywords: tetrahydrocamptothecin; camptothecin; nitro; chloroform; mmol
Prior art date: 1982-09-10
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

JP15681482A

Other languages

English (en)

Japanese (ja)

Other versions

JPS5946284A (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.)

1982-09-10

Filing date

1982-09-10

Publication date

1990-02-28

1982-09-10 Application filed by Yakult Honsha Co Ltd filed Critical Yakult Honsha Co Ltd

1982-09-10 Priority to JP15681482A priority Critical patent/JPS5946284A/ja

1984-03-15 Publication of JPS5946284A publication Critical patent/JPS5946284A/ja

1990-02-28 Publication of JPH029032B2 publication Critical patent/JPH029032B2/ja

Status Granted legal-status Critical Current

Links

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 claims description 16
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 15
238000004519 manufacturing process Methods 0.000 claims description 14
KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 13
229940127093 camptothecin Drugs 0.000 claims description 13
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 13
238000010531 catalytic reduction reaction Methods 0.000 claims description 7
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 6
229910017604 nitric acid Inorganic materials 0.000 claims description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 36
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
238000003756 stirring Methods 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
239000000243 solution Substances 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
150000001875 compounds Chemical class 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
229910052739 hydrogen Inorganic materials 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 7
239000002904 solvent Substances 0.000 description 7
239000003054 catalyst Substances 0.000 description 6
238000000354 decomposition reaction Methods 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 5
VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
239000005457 ice water Substances 0.000 description 5
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 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
239000012954 diazonium Substances 0.000 description 4
150000001989 diazonium salts Chemical class 0.000 description 4
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
238000001035 drying Methods 0.000 description 3
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 3
229910003446 platinum oxide Inorganic materials 0.000 description 3
238000010898 silica gel chromatography Methods 0.000 description 3
235000010288 sodium nitrite Nutrition 0.000 description 3
239000000126 substance Substances 0.000 description 3
KXJNTORVTHBKGW-UHFFFAOYSA-N 11-hydroxycamptothecin Natural products OC1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 KXJNTORVTHBKGW-UHFFFAOYSA-N 0.000 description 2
FWFUSMMVFVVERM-UHFFFAOYSA-N 2-(1,4-dioxan-2-yl)acetic acid Chemical compound OC(=O)CC1COCCO1 FWFUSMMVFVVERM-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
230000001093 anti-cancer Effects 0.000 description 2
125000003118 aryl group Chemical class 0.000 description 2
KXJNTORVTHBKGW-FQEVSTJZSA-N chembl39011 Chemical compound OC1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 KXJNTORVTHBKGW-FQEVSTJZSA-N 0.000 description 2
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 2
239000013078 crystal Substances 0.000 description 2
229940045803 cuprous chloride Drugs 0.000 description 2
238000000921 elemental analysis Methods 0.000 description 2
229910000042 hydrogen bromide Inorganic materials 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
239000000203 mixture Substances 0.000 description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
229910052697 platinum Inorganic materials 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
238000006722 reduction reaction Methods 0.000 description 2
238000010992 reflux Methods 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
NUCVEPZRPYQXBX-UHFFFAOYSA-N 11-methoxycamptothecin Chemical compound COC1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 NUCVEPZRPYQXBX-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
241000759905 Camptotheca acuminata Species 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
206010028980 Neoplasm Diseases 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
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
125000004442 acylamino group Chemical group 0.000 description 1
229930013930 alkaloid Natural products 0.000 description 1
150000003797 alkaloid derivatives Chemical class 0.000 description 1
230000002152 alkylating effect 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
230000015572 biosynthetic process Effects 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000007336 electrophilic substitution reaction Methods 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
239000007788 liquid Substances 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
239000012046 mixed solvent Substances 0.000 description 1
238000006396 nitration reaction Methods 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
230000006911 nucleation Effects 0.000 description 1
238000001668 nucleic acid synthesis Methods 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000001953 recrystallisation Methods 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
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007858 starting material Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1

Landscapes

Nitrogen Condensed Heterocyclic Rings (AREA)

JP15681482A 1982-09-10 1982-09-10 １１−ニトロカンプトテシン誘導体およびその製造法 Granted JPS5946284A (ja)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
JP15681482A JPS5946284A (ja)	1982-09-10	1982-09-10	１１−ニトロカンプトテシン誘導体およびその製造法

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
JP15681482A JPS5946284A (ja)	1982-09-10	1982-09-10	１１−ニトロカンプトテシン誘導体およびその製造法

Publications (2)

Publication Number	Publication Date
JPS5946284A JPS5946284A (ja)	1984-03-15
JPH029032B2 true JPH029032B2 (de)	1990-02-28

Family

ID=15635908

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP15681482A Granted JPS5946284A (ja)	1982-09-10	1982-09-10	１１−ニトロカンプトテシン誘導体およびその製造法

Country Status (1)

Country	Link
JP (1)	JPS5946284A (de)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5122526A (en) *	1987-03-31	1992-06-16	Research Triangle Institute	Camptothecin and analogs thereof and pharmaceutical compositions and method using them
US5106742A (en) *	1987-03-31	1992-04-21	Wall Monroe E	Camptothecin analogs as potent inhibitors of topoisomerase I
US5364858A (en) *	1987-03-31	1994-11-15	Research Triangle Institute	Camptothecin analogs as potent inhibitors of topoisomerase I
US5227380A (en) *	1987-03-31	1993-07-13	Research Triangle Institute	Pharmaceutical compositions and methods employing camptothecins
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
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
CN100334089C (zh) *	2004-07-21	2007-08-29	王洋	一种9－硝基喜树碱的生产方法

1982
- 1982-09-10 JP JP15681482A patent/JPS5946284A/ja active Granted

Also Published As

Publication number	Publication date
JPS5946284A (ja)	1984-03-15

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WO2001070747A1 (fr)	2001-09-27	Procede de production de camptothecine
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JPS6247192B2 (de)	1987-10-06
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