DK142815B - Analogifremgangsmåde til fremstilling af 4-desacetoxyvincristin eller syreadditionssalte deraf. - Google Patents
Analogifremgangsmåde til fremstilling af 4-desacetoxyvincristin eller syreadditionssalte deraf. Download PDFInfo
- Publication number
- DK142815B DK142815B DK78777AA DK78777A DK142815B DK 142815 B DK142815 B DK 142815B DK 78777A A DK78777A A DK 78777AA DK 78777 A DK78777 A DK 78777A DK 142815 B DK142815 B DK 142815B
- Authority
- DK
- Denmark
- Prior art keywords
- desacetoxyquincristine
- mixture
- desacetoxyvinblastine
- solution
- acid addition
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims description 13
- 238000000034 method Methods 0.000 title claims description 12
- 150000003839 salts Chemical class 0.000 title claims description 10
- 238000002360 preparation method Methods 0.000 title claims description 6
- LVINNLJJGRZGKQ-VMJLQBTBSA-N 4-Desacetoxyvinblastine Natural products CC[C@]1(O)C[C@@H]2CN(CC[C@H]3[C@@H](Nc4ccccc34)[C@@](C2)(C(=O)OC)c5cc6c(cc5OC)N(C)[C@H]7[C@](O)(C[C@]8(CC)C=CCN9CC[C@]67[C@H]89)C(=O)OC)C1 LVINNLJJGRZGKQ-VMJLQBTBSA-N 0.000 claims description 18
- OBMKRZCOTHZPOB-UDMDOTTKSA-N 4-desacetoxyvinblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@](C[C@@]6(C=CCN([C@H]56)CC4)CC)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 OBMKRZCOTHZPOB-UDMDOTTKSA-N 0.000 claims description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 39
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
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- 239000000203 mixture Substances 0.000 description 22
- 239000000243 solution Substances 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
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- YIQATJBOCJPFCF-XQLDGQACSA-N methyl (1R,9R,10S,11R,12R,19R)-12-ethyl-4-[(13S,15R,17S)-17-ethyl-17-hydroxy-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraen-13-yl]-8-formyl-10,11-dihydroxy-5-methoxy-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate Chemical compound CC[C@]1(O)C[C@@H]2CN(C1)CCc1c([nH]c3ccccc13)[C@@](C2)(C(=O)OC)c1cc2c(cc1OC)N(C=O)[C@@H]1[C@]22CCN3CC=C[C@](CC)([C@@H]23)[C@@H](O)[C@]1(O)C(=O)OC YIQATJBOCJPFCF-XQLDGQACSA-N 0.000 description 3
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- 229910052763 palladium Inorganic materials 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 3
- 230000001875 tumorinhibitory effect Effects 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
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- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
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- 239000012429 reaction media Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 229960003048 vinblastine Drugs 0.000 description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- 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
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
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- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
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- 206010029350 Neurotoxicity Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- RSPISYXLHRIGJD-UHFFFAOYSA-N OOOO Chemical compound OOOO RSPISYXLHRIGJD-UHFFFAOYSA-N 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 241000863480 Vinca Species 0.000 description 1
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- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
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- 150000008064 anhydrides Chemical class 0.000 description 1
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- 235000006708 antioxidants Nutrition 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
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- 239000003637 basic solution Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical class [H]N([H])C(*)=O 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- SOCTUWSJJQCPFX-UHFFFAOYSA-N dichromate(2-) Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O SOCTUWSJJQCPFX-UHFFFAOYSA-N 0.000 description 1
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- GLDSBTCHEGZWCV-HLTPFJCJSA-N leuroformine Chemical compound C([C@]1([C@@H]2O1)CC)N(CCC=1C3=CC=CC=C3NC=11)C[C@H]2C[C@]1(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C=O)=C2C=C1OC GLDSBTCHEGZWCV-HLTPFJCJSA-N 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 238000001819 mass spectrum Methods 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
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/04—Dimeric indole alkaloids, e.g. vincaleucoblastine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU76RI00000586A HU172183B (hu) | 1976-02-24 | 1976-02-24 | Spsosob poluchenija 4-dezacetoksi-vinkhristina i kislotodobavochnykh solejj |
| HURI000586 | 1976-02-24 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK78777A DK78777A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1977-08-25 |
| DK142815B true DK142815B (da) | 1981-02-02 |
| DK142815C DK142815C (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1981-08-24 |
Family
ID=11000995
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK78777AA DK142815B (da) | 1976-02-24 | 1977-02-23 | Analogifremgangsmåde til fremstilling af 4-desacetoxyvincristin eller syreadditionssalte deraf. |
Country Status (15)
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5891011A (ja) * | 1981-11-25 | 1983-05-30 | Toshiba Ceramics Co Ltd | α相含有率の高い窒化珪素粉末の製造方法 |
| CN112521408B (zh) * | 2020-12-16 | 2022-05-17 | 广州白云山汉方现代药业有限公司 | 一种双吲哚类生物碱化合物及其制备方法与应用 |
| CN114933604A (zh) * | 2021-12-10 | 2022-08-23 | 广州白云山汉方现代药业有限公司 | 一种长春新碱类手性化合物杂质及其制备方法与应用 |
-
1976
- 1976-02-24 HU HU76RI00000586A patent/HU172183B/hu unknown
-
1977
- 1977-02-08 SE SE7701377A patent/SE430694B/xx not_active IP Right Cessation
- 1977-02-09 AT AT84177A patent/AT353429B/de not_active IP Right Cessation
- 1977-02-10 AU AU22173/77A patent/AU506508B2/en not_active Expired
- 1977-02-10 CH CH162477A patent/CH627185A5/de not_active IP Right Cessation
- 1977-02-15 DE DE19772706366 patent/DE2706366A1/de not_active Withdrawn
- 1977-02-17 IL IL51486A patent/IL51486A/xx unknown
- 1977-02-22 FR FR7705059A patent/FR2342295A1/fr active Granted
- 1977-02-22 SU SU772453504A patent/SU673174A3/ru active
- 1977-02-22 BE BE175146A patent/BE851697A/xx not_active IP Right Cessation
- 1977-02-23 JP JP1824577A patent/JPS52102300A/ja active Pending
- 1977-02-23 GB GB7677/77A patent/GB1525372A/en not_active Expired
- 1977-02-23 NL NL7701948A patent/NL7701948A/xx not_active Application Discontinuation
- 1977-02-23 CA CA272,431A patent/CA1094551A/en not_active Expired
- 1977-02-23 DK DK78777AA patent/DK142815B/da not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NL7701948A (nl) | 1977-08-26 |
| JPS52102300A (en) | 1977-08-27 |
| AT353429B (de) | 1979-11-12 |
| GB1525372A (en) | 1978-09-20 |
| BE851697A (fr) | 1977-06-16 |
| IL51486A (en) | 1979-10-31 |
| CA1094551A (en) | 1981-01-27 |
| DE2706366A1 (de) | 1977-08-25 |
| FR2342295A1 (fr) | 1977-09-23 |
| FR2342295B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1980-09-05 |
| SU673174A3 (ru) | 1979-07-05 |
| AU2217377A (en) | 1978-08-17 |
| DK78777A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1977-08-25 |
| DK142815C (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1981-08-24 |
| HU172183B (hu) | 1978-06-28 |
| SE7701377L (sv) | 1977-08-25 |
| SE430694B (sv) | 1983-12-05 |
| IL51486A0 (en) | 1977-04-29 |
| CH627185A5 (en) | 1981-12-31 |
| ATA84177A (de) | 1979-04-15 |
| AU506508B2 (en) | 1980-01-10 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |