SE467874B - Framstaellning av vinblastin och vinkristin - Google Patents
Framstaellning av vinblastin och vinkristinInfo
- Publication number
- SE467874B SE467874B SE8800170A SE8800170A SE467874B SE 467874 B SE467874 B SE 467874B SE 8800170 A SE8800170 A SE 8800170A SE 8800170 A SE8800170 A SE 8800170A SE 467874 B SE467874 B SE 467874B
- Authority
- SE
- Sweden
- Prior art keywords
- formula
- alkyl
- alk
- product
- aryl
- Prior art date
Links
- 238000000034 method Methods 0.000 claims description 35
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 230000008569 process Effects 0.000 claims description 27
- 150000002081 enamines Chemical class 0.000 claims description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 24
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 239000000047 product Substances 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- 230000009467 reduction Effects 0.000 claims description 15
- 238000005273 aeration Methods 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 230000003647 oxidation Effects 0.000 claims description 14
- 238000007254 oxidation reaction Methods 0.000 claims description 14
- 238000006213 oxygenation reaction Methods 0.000 claims description 14
- 229960003048 vinblastine Drugs 0.000 claims description 14
- 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 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- 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 claims description 13
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 12
- -1 N-substituted 1 , 4-dihydronicotinamides Chemical class 0.000 claims description 11
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 239000012298 atmosphere Substances 0.000 claims description 10
- 238000005859 coupling reaction Methods 0.000 claims description 10
- 125000001041 indolyl group Chemical group 0.000 claims description 10
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 10
- 125000003107 substituted aryl group Chemical group 0.000 claims description 10
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 claims description 9
- 230000001105 regulatory effect Effects 0.000 claims description 9
- 239000005515 coenzyme Substances 0.000 claims description 8
- 238000006062 fragmentation reaction Methods 0.000 claims description 7
- 238000003786 synthesis reaction Methods 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- 150000001340 alkali metals Chemical class 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical group C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 claims description 6
- 238000002955 isolation Methods 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
- 150000001204 N-oxides Chemical class 0.000 claims description 5
- 230000008878 coupling Effects 0.000 claims description 5
- 238000010168 coupling process Methods 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 229930013930 alkaloid Natural products 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- 229910021645 metal ion Inorganic materials 0.000 claims description 4
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 4
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 3
- 239000012346 acetyl chloride Substances 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 150000002432 hydroperoxides Chemical class 0.000 claims description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 229960004528 vincristine Drugs 0.000 claims description 3
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 3
- 239000000539 dimer Substances 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims 6
- 238000000935 solvent evaporation Methods 0.000 claims 5
- 229940122803 Vinca alkaloid Drugs 0.000 claims 2
- 150000004075 acetic anhydrides Chemical class 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 229930195733 hydrocarbon Natural products 0.000 claims 2
- 150000002430 hydrocarbons Chemical class 0.000 claims 2
- QUIJMHDIAFOPRK-UHFFFAOYSA-N 1-cyclooctylazocane Chemical group C1CCCCCCC1N1CCCCCCC1 QUIJMHDIAFOPRK-UHFFFAOYSA-N 0.000 claims 1
- 241001661930 Aspidosperma Species 0.000 claims 1
- 241001246918 Tabernanthe iboga Species 0.000 claims 1
- 150000003797 alkaloid derivatives Chemical class 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 claims 1
- 239000000543 intermediate Substances 0.000 description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 15
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000012279 sodium borohydride Substances 0.000 description 9
- 229910000033 sodium borohydride Inorganic materials 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- FVTCRASFADXXNN-SCRDCRAPSA-N flavin mononucleotide Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-SCRDCRAPSA-N 0.000 description 5
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- 229940013640 flavin mononucleotide Drugs 0.000 description 5
- FVTCRASFADXXNN-UHFFFAOYSA-N flavin mononucleotide Natural products OP(=O)(O)OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-UHFFFAOYSA-N 0.000 description 5
- 235000019231 riboflavin-5'-phosphate Nutrition 0.000 description 5
- CXBGOBGJHGGWIE-IYJDUVQVSA-N vindoline Chemical compound CN([C@H]1[C@](O)([C@@H]2OC(C)=O)C(=O)OC)C3=CC(OC)=CC=C3[C@]11CCN3CC=C[C@]2(CC)[C@@H]13 CXBGOBGJHGGWIE-IYJDUVQVSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
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- 150000001298 alcohols Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- GKWYINOZGDHWRA-UHFFFAOYSA-N catharanthine Natural products C1C(CC)(O)CC(CC2C(=O)OC)CN1CCC1=C2NC2=CC=CC=C12 GKWYINOZGDHWRA-UHFFFAOYSA-N 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- CMNUYDSETOTBDE-UHFFFAOYSA-N 1-benzyl-4h-pyridine-3-carboxamide Chemical compound C1=CCC(C(=O)N)=CN1CC1=CC=CC=C1 CMNUYDSETOTBDE-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- AQXVANXWKSPKMX-UHFFFAOYSA-N Catharinin Natural products C=1C(C23C(C(C(OC(C)=O)C4(CC)C=CCN(C34)CC2)(O)C(=O)OC)N2C)=C2C=C(OC)C=1C1(C(=O)OC)CC(CC(=O)CC)CN(C=O)CCC2=C1NC1=CC=CC=C21 AQXVANXWKSPKMX-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 239000012448 Lithium borohydride Substances 0.000 description 3
- 238000006972 Polonovski rearrangement reaction Methods 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
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- AQXVANXWKSPKMX-RSAMFGMZSA-N catharinine Chemical compound 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@H](CC(=O)CC)CN(C=O)CCC2=C1NC1=CC=CC=C21 AQXVANXWKSPKMX-RSAMFGMZSA-N 0.000 description 3
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- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 3
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- 235000019341 magnesium sulphate Nutrition 0.000 description 3
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- 238000004007 reversed phase HPLC Methods 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 2
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- 229910052742 iron Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 229910052758 niobium Inorganic materials 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000005371 permeation separation Methods 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine 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-CFWMRBGOSA-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)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000527897A CA1341261C (en) | 1987-01-22 | 1987-01-22 | Process for the synthesis of 3',4'-anhydrovinblastine, vinblastine and vincristine |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| SE8800170D0 SE8800170D0 (sv) | 1988-01-20 |
| SE8800170L SE8800170L (sv) | 1988-07-23 |
| SE467874B true SE467874B (sv) | 1992-09-28 |
Family
ID=4134803
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE8800170A SE467874B (sv) | 1987-01-22 | 1988-01-20 | Framstaellning av vinblastin och vinkristin |
Country Status (11)
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1341262C (en) * | 1987-08-06 | 2001-06-26 | Camille A. Boulet | A new process of the synthesis of 3',4'-anhydrovinblastine, vinblastine and vincristine |
| US5047528A (en) * | 1987-01-22 | 1991-09-10 | University Of Bristish Columbia | Process of synthesis of vinblastine and vincristine |
| USRE37449E1 (en) | 1987-02-06 | 2001-11-13 | University Of British Columbia | Process of synthesis of 3′,4′-anhydrovinblastine, vinblastine and vincristine |
| US5037977A (en) * | 1988-08-11 | 1991-08-06 | Mitsui Petrochemical Industries Ltd. | Method for production of dimeric alkaloids |
| US5432279A (en) * | 1989-03-04 | 1995-07-11 | Mitsui Petrochemical Industries, Inc. | Process for the preparation of binary indole alkaloids |
| CA2011389A1 (en) * | 1989-03-04 | 1990-09-04 | Naoya Sakamoto | Process for the preparation of binary indole alkaloids |
| FR2779146B1 (fr) * | 1998-06-02 | 2002-01-18 | Roowin | Nouveaux derives de vinca-alcaloides et procedes de preparation |
| CN103936769B (zh) * | 2014-04-30 | 2016-10-05 | 淮海工学院 | 一种制备高光学纯脱水长春碱的方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2296418B1 (enrdf_load_stackoverflow) * | 1974-12-30 | 1978-07-21 | Anvar | |
| US4279817A (en) * | 1975-05-30 | 1981-07-21 | The United States Of America As Represented By The Department Of Health & Human Services | Method for producing dimer alkaloids |
| GB1551054A (en) * | 1976-03-04 | 1979-08-22 | Atta Ur Rahman | Syntheses of vinblastine vincristine and vinrosidine |
| FR2358412A1 (fr) * | 1976-07-13 | 1978-02-10 | Parcor | Procede de preparation de la vincamine et d'alcaloides apparentes |
-
1987
- 1987-01-22 CA CA000527897A patent/CA1341261C/en not_active Expired - Fee Related
-
1988
- 1988-01-20 SE SE8800170A patent/SE467874B/sv not_active IP Right Cessation
- 1988-01-20 DE DE3801450A patent/DE3801450C2/de not_active Expired - Fee Related
- 1988-01-21 GB GB8801296A patent/GB2204036B/en not_active Expired - Lifetime
- 1988-01-21 ZA ZA88408A patent/ZA88408B/xx unknown
- 1988-01-21 IL IL85154A patent/IL85154A/xx not_active IP Right Cessation
- 1988-01-21 NL NL8800134A patent/NL8800134A/nl not_active Application Discontinuation
- 1988-01-21 CH CH206/88A patent/CH675724A5/de not_active IP Right Cessation
- 1988-01-21 IT IT8819156A patent/IT1215751B/it active
- 1988-01-21 FR FR8800650A patent/FR2611202A1/fr active Granted
- 1988-01-22 JP JP63013473A patent/JPH0613531B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DE3801450C2 (de) | 1999-02-25 |
| IL85154A0 (en) | 1988-06-30 |
| ZA88408B (en) | 1989-04-26 |
| IL85154A (en) | 1992-08-18 |
| GB8801296D0 (en) | 1988-02-17 |
| DE3801450A1 (de) | 1988-08-18 |
| SE8800170D0 (sv) | 1988-01-20 |
| IT8819156A0 (it) | 1988-01-21 |
| CA1341261C (en) | 2001-06-26 |
| SE8800170L (sv) | 1988-07-23 |
| JPH01131187A (ja) | 1989-05-24 |
| CH675724A5 (enrdf_load_stackoverflow) | 1990-10-31 |
| FR2611202A1 (fr) | 1988-08-26 |
| IT1215751B (it) | 1990-02-22 |
| GB2204036B (en) | 1991-03-27 |
| JPH0613531B2 (ja) | 1994-02-23 |
| GB2204036A (en) | 1988-11-02 |
| NL8800134A (nl) | 1988-08-16 |
| FR2611202B1 (enrdf_load_stackoverflow) | 1994-08-19 |
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