CH676711A5 - - Google Patents

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Info

Publication number: CH676711A5
Authority: CH; Switzerland
Prior art keywords: formula; enamine; alk; alkyl; solution
Prior art date: 1987-08-06

Application number

CH2974/88A

Other languages

German (de)

English (en)

Inventor

James P Kutney

Lewis S L Choi

Jun Nakano

Hiroki Tsukamoto

Camille A Boulet

Michael Mchugh

Original Assignee

Univ British Columbia

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.)

1987-08-06

Filing date

1988-08-05

Publication date

1991-02-28

1988-08-05 Application filed by Univ British Columbia filed Critical Univ British Columbia

1991-02-28 Publication of CH676711A5 publication Critical patent/CH676711A5/de

Links

150000002081 enamines Chemical class 0.000 claims description 75
238000000034 method Methods 0.000 claims description 54
239000000543 intermediate Substances 0.000 claims description 50
239000000243 solution Substances 0.000 claims description 39
239000000047 product Substances 0.000 claims description 29
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 27
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 23
125000000217 alkyl group Chemical group 0.000 claims description 22
230000015572 biosynthetic process Effects 0.000 claims description 22
229960003048 vinblastine Drugs 0.000 claims description 22
238000007254 oxidation reaction Methods 0.000 claims description 20
230000003647 oxidation Effects 0.000 claims description 18
239000002904 solvent Substances 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 14
FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 claims description 14
125000003118 aryl group Chemical group 0.000 claims description 13
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
150000001875 compounds Chemical class 0.000 claims description 12
-1 1,4-dihydropyridine compound Chemical class 0.000 claims description 10
238000010790 dilution Methods 0.000 claims description 10
239000012895 dilution Substances 0.000 claims description 10
230000002829 reductive effect Effects 0.000 claims description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
238000002955 isolation Methods 0.000 claims description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical group C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 claims description 8
238000001704 evaporation Methods 0.000 claims description 7
125000001041 indolyl group Chemical group 0.000 claims description 7
238000002360 preparation method Methods 0.000 claims description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
JXLYSJRDGCGARV-PJXZDTQASA-N Leurosidine 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-PJXZDTQASA-N 0.000 claims description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
JXLYSJRDGCGARV-KSNABSRWSA-N ac1l29ym 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-KSNABSRWSA-N 0.000 claims description 6
238000005273 aeration Methods 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
239000005515 coenzyme Substances 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
229910052783 alkali metal Inorganic materials 0.000 claims description 5
150000001340 alkali metals Chemical class 0.000 claims description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
239000003960 organic solvent Substances 0.000 claims description 5
125000000547 substituted alkyl group Chemical group 0.000 claims description 5
125000003107 substituted aryl group Chemical group 0.000 claims description 5
YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 4
150000004075 acetic anhydrides Chemical class 0.000 claims description 4
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 4
239000012346 acetyl chloride Substances 0.000 claims description 4
239000007795 chemical reaction product Substances 0.000 claims description 4
230000008020 evaporation Effects 0.000 claims description 4
238000005580 one pot reaction Methods 0.000 claims description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
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 3
150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 3
238000011065 in-situ storage Methods 0.000 claims description 3
229910052757 nitrogen Inorganic materials 0.000 claims description 3
150000001204 N-oxides Chemical class 0.000 claims description 2
229940122803 Vinca alkaloid Drugs 0.000 claims description 2
239000003125 aqueous solvent Substances 0.000 claims description 2
238000003776 cleavage reaction Methods 0.000 claims description 2
150000002432 hydroperoxides Chemical class 0.000 claims description 2
229910021645 metal ion Inorganic materials 0.000 claims description 2
230000008878 coupling Effects 0.000 claims 1
238000010168 coupling process Methods 0.000 claims 1
238000005859 coupling reaction Methods 0.000 claims 1
238000007865 diluting Methods 0.000 claims 1
238000001914 filtration Methods 0.000 claims 1
238000000935 solvent evaporation Methods 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
238000004007 reversed phase HPLC Methods 0.000 description 16
238000006243 chemical reaction Methods 0.000 description 14
238000003786 synthesis reaction Methods 0.000 description 11
DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 10
229910052786 argon Inorganic materials 0.000 description 10
239000003638 chemical reducing agent Substances 0.000 description 10
238000004458 analytical method Methods 0.000 description 9
230000000694 effects Effects 0.000 description 9
239000012279 sodium borohydride Substances 0.000 description 9
229910000033 sodium borohydride Inorganic materials 0.000 description 9
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 8
239000011734 sodium Substances 0.000 description 8
150000002431 hydrogen Chemical class 0.000 description 7
238000004519 manufacturing process Methods 0.000 description 7
229960003966 nicotinamide Drugs 0.000 description 7
239000011570 nicotinamide Substances 0.000 description 7
230000001590 oxidative effect Effects 0.000 description 7
229910052708 sodium Inorganic materials 0.000 description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
WVTGEXAIVZDLCR-UHFFFAOYSA-N Vindoline Natural products CC1C2CN3CCCC14CCC5Nc6ccccc6C25C34 WVTGEXAIVZDLCR-UHFFFAOYSA-N 0.000 description 6
GKWYINOZGDHWRA-UHFFFAOYSA-N catharanthine Natural products C1C(CC)(O)CC(CC2C(=O)OC)CN1CCC1=C2NC2=CC=CC=C12 GKWYINOZGDHWRA-UHFFFAOYSA-N 0.000 description 6
238000011002 quantification Methods 0.000 description 6
238000010626 work up procedure Methods 0.000 description 6
CMKFQVZJOWHHDV-DYHNYNMBSA-N catharanthine Chemical compound C([C@@H]1C=C([C@@H]2[C@@]3(C1)C(=O)OC)CC)N2CCC1=C3NC2=CC=CC=C12 CMKFQVZJOWHHDV-DYHNYNMBSA-N 0.000 description 5
235000005152 nicotinamide Nutrition 0.000 description 5
CXBGOBGJHGGWIE-ACSXSLCXSA-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-ACSXSLCXSA-N 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
SASWULSUPROHRT-MCIGMTSASA-N Vindorosine Natural products CN([C@H]1[C@](O)([C@@H]2OC(C)=O)C(=O)OC)C3=CC=CC=C3[C@@]11CCN3CC=C[C@]2(CC)[C@@H]13 SASWULSUPROHRT-MCIGMTSASA-N 0.000 description 4
229930013930 alkaloid Natural products 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
150000001733 carboxylic acid esters Chemical class 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 3
150000001734 carboxylic acid salts Chemical class 0.000 description 3
125000000524 functional group Chemical group 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
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 description 3
229960004528 vincristine Drugs 0.000 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 description 3
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 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
JIJVOHRWYUICGU-UHFFFAOYSA-N 1-benzhydryl-4h-pyridine-3-carboxamide Chemical compound C1=CCC(C(=O)N)=CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 JIJVOHRWYUICGU-UHFFFAOYSA-N 0.000 description 2
WJNYVKCAEHASOF-UHFFFAOYSA-N 1-benzyl-4h-pyridine-3-carbonitrile Chemical compound C1=CCC(C#N)=CN1CC1=CC=CC=C1 WJNYVKCAEHASOF-UHFFFAOYSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
239000012300 argon atmosphere Substances 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
239000012043 crude product Substances 0.000 description 2
238000010828 elution Methods 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
239000000284 extract Substances 0.000 description 2
238000000605 extraction Methods 0.000 description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
239000013067 intermediate product Substances 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 2
239000000203 mixture Substances 0.000 description 2
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
KGUMNRYFUFLBGA-UHFFFAOYSA-N 1,4-dihydropyridine-3-carboxamide Chemical class NC(=O)C1=CNC=CC1 KGUMNRYFUFLBGA-UHFFFAOYSA-N 0.000 description 1
QUIJMHDIAFOPRK-UHFFFAOYSA-N 1-cyclooctylazocane Chemical group C1CCCCCCC1N1CCCCCCC1 QUIJMHDIAFOPRK-UHFFFAOYSA-N 0.000 description 1
PTXVSDKCUJCCLC-UHFFFAOYSA-N 1-hydroxyindole Chemical compound C1=CC=C2N(O)C=CC2=C1 PTXVSDKCUJCCLC-UHFFFAOYSA-N 0.000 description 1
RVCKCEDKBVEEHL-UHFFFAOYSA-N 2,3,4,5,6-pentachlorobenzyl alcohol Chemical compound OCC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl RVCKCEDKBVEEHL-UHFFFAOYSA-N 0.000 description 1
PCRICPYPVZKEBZ-UHFFFAOYSA-N 2,3-diphenylpropanoic acid Chemical compound C=1C=CC=CC=1C(C(=O)O)CC1=CC=CC=C1 PCRICPYPVZKEBZ-UHFFFAOYSA-N 0.000 description 1
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 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
241001661930 Aspidosperma Species 0.000 description 1
241000208328 Catharanthus Species 0.000 description 1
NVVDQMVGALBDGE-UHFFFAOYSA-N Dihydrocatharanthin Natural products C1C2(C(=O)OC)C3C(CC)CC1CN3CCC1=C2NC2=CC=CC=C12 NVVDQMVGALBDGE-UHFFFAOYSA-N 0.000 description 1
DIIWSYPKAJVXBV-UHFFFAOYSA-N Hantzch dihydropyridine Natural products CCOC(=O)C1=CC(C(=O)OCC)=C(C)N=C1C DIIWSYPKAJVXBV-UHFFFAOYSA-N 0.000 description 1
101100108967 Human herpesvirus 6B (strain Z29) U70 gene Proteins 0.000 description 1
229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
239000007987 MES buffer Substances 0.000 description 1
241001676573 Minium Species 0.000 description 1
ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
LXAOWPZJTWFMLM-UHFFFAOYSA-N NC(C(CCC1)N1NCC1=CNC=CC1)=O Chemical compound NC(C(CCC1)N1NCC1=CNC=CC1)=O LXAOWPZJTWFMLM-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
238000006972 Polonovski rearrangement reaction Methods 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
241001246918 Tabernanthe iboga Species 0.000 description 1
241000863480 Vinca Species 0.000 description 1
241000700605 Viruses Species 0.000 description 1
150000003797 alkaloid derivatives Chemical class 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
230000000118 anti-neoplastic effect Effects 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
239000012062 aqueous buffer Substances 0.000 description 1
DMHZGJLWEIEBRK-UHFFFAOYSA-N argon methanol Chemical compound [Ar].OC DMHZGJLWEIEBRK-UHFFFAOYSA-N 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
LJXTYJXBORAIHX-UHFFFAOYSA-N diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1 LJXTYJXBORAIHX-UHFFFAOYSA-N 0.000 description 1
238000003113 dilution method Methods 0.000 description 1
239000000539 dimer Substances 0.000 description 1
239000007862 dimeric product Substances 0.000 description 1
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000001307 helium Substances 0.000 description 1
229910052734 helium Inorganic materials 0.000 description 1
SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
150000002466 imines Chemical class 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
229910052754 neon Inorganic materials 0.000 description 1
GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 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
230000000737 periodic effect Effects 0.000 description 1
125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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
238000010926 purge Methods 0.000 description 1
238000011946 reduction process Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000003756 stirring Methods 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
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
239000003643 water by type Substances 0.000 description 1
125000005023 xylyl group Chemical group 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

CH2974/88A 1987-08-06 1988-08-05 CH676711A5 (da)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA000543832A CA1341262C (en)	1987-08-06	1987-08-06	A new process of the synthesis of 3',4'-anhydrovinblastine, vinblastine and vincristine

Publications (1)

Publication Number	Publication Date
CH676711A5 true CH676711A5 (da)	1991-02-28

Family

ID=4136214

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH2974/88A CH676711A5 (da)	1987-08-06	1988-08-05

Country Status (12)

Country	Link
JP (1)	JPH0613532B2 (da)
AU (1)	AU617342B2 (da)
BE (1)	BE1003228A4 (da)
CA (1)	CA1341262C (da)
CH (1)	CH676711A5 (da)
DE (1)	DE3826412A1 (da)
GB (1)	GB2215331B (da)
HU (1)	HU208829B (da)
IT (1)	IT1227155B (da)
NL (1)	NL8801966A (da)
SE (1)	SE467875B (da)
ZA (1)	ZA885765B (da)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
US5432279A (en) *	1989-03-04	1995-07-11	Mitsui Petrochemical Industries, Inc.	Process for the preparation of binary indole alkaloids
CA2056799C (en) *	1990-11-30	2002-01-01	Hiroshi Ikawa	1,4-dihydropyridine derivatives and methods of producing the same
JP3010151U (ja) *	1994-04-26	1995-04-25	スミ子片山	切込みのついた筒形食器収納ケース。
FR2779146B1 (fr) *	1998-06-02	2002-01-18	Roowin	Nouveaux derives de vinca-alcaloides et procedes de preparation

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
HU195513B (en) *	1984-10-16	1988-05-30	Richter Gedeon Vegyeszet	Process for producing stable solutions of alkaloides with bis-indole skeleton
AU590873B2 (en) *	1985-03-12	1989-11-23	University Of Vermont And State Agricultural College, The	Synthesis of vinblastine and vincristine type compounds
CA1341261C (en) *	1987-01-22	2001-06-26	James P. Kutney	Process for the synthesis of 3',4'-anhydrovinblastine, vinblastine and vincristine

1987
- 1987-08-06 CA CA000543832A patent/CA1341262C/en not_active Expired - Fee Related
1988
- 1988-08-03 SE SE8802813A patent/SE467875B/sv not_active IP Right Cessation
- 1988-08-03 DE DE3826412A patent/DE3826412A1/de not_active Ceased
- 1988-08-05 CH CH2974/88A patent/CH676711A5/de not_active IP Right Cessation
- 1988-08-05 IT IT8821678A patent/IT1227155B/it active
- 1988-08-05 BE BE8800908A patent/BE1003228A4/fr not_active IP Right Cessation
- 1988-08-05 NL NL8801966A patent/NL8801966A/nl not_active Application Discontinuation
- 1988-08-05 ZA ZA885765A patent/ZA885765B/xx unknown
- 1988-08-05 AU AU20512/88A patent/AU617342B2/en not_active Ceased
- 1988-08-06 JP JP63196999A patent/JPH0613532B2/ja not_active Expired - Lifetime
- 1988-08-08 GB GB8818765A patent/GB2215331B/en not_active Expired - Lifetime
- 1988-08-08 HU HU884126A patent/HU208829B/hu not_active IP Right Cessation

Also Published As

Publication number	Publication date
GB8818765D0 (en)	1988-09-07
NL8801966A (nl)	1989-03-01
AU2051288A (en)	1989-02-09
HU208829B (en)	1994-01-28
IT1227155B (it)	1991-03-19
SE8802813D0 (sv)	1988-08-03
JPH0613532B2 (ja)	1994-02-23
HUT50351A (en)	1990-01-29
GB2215331B (en)	1992-01-02
SE8802813L (sv)	1989-02-07
BE1003228A4 (fr)	1992-02-04
ZA885765B (en)	1989-09-27
IT8821678A0 (it)	1988-08-05
JPH01151590A (ja)	1989-06-14
DE3826412A1 (de)	1989-02-16
GB2215331A (en)	1989-09-20
SE467875B (sv)	1992-09-28
AU617342B2 (en)	1991-11-28
CA1341262C (en)	2001-06-26

Legal Events

Date	Code	Title	Description
1999-04-15	PL	Patent ceased

Publication	Publication Date	Title
DE2558124C2 (da)	1991-04-18
DE2622894A1 (de)	1976-12-16	Verfahren zur synthese eines dimeren mit einer indoleinheit und einer dihydroindoleinheit
DE3601285C2 (da)	1988-07-21
DE3525564A1 (de)	1987-02-05	Tricyclische verbindungen mit indolstruktur, verfahren zu ihrer herstellung und deren verwendung als arzneimittel
EP0434057B1 (de)	1996-07-31	Indolocarbazol-Derivate, Verfahren zu deren Herstellung und deren Verwendung
CH676711A5 (da)	1991-02-28
DE2330912B2 (de)	1978-05-18	Verfahren zur Herstellung von Bromergolinverbindungen
EP0602083B1 (de)	1995-05-31	Verfahren zur herstellung von 5,6-dihydroxyindolinen
DE2846321A1 (de)	1979-05-31	Verfahren zur herstellung von rifamycinen
DE3801450C2 (de)	1999-02-25	Verfahren für die Herstellung von Dimeralkaloidverbindungen, insbesondere von 3', 4'-Dihydrovinblastin, Vinblastin und Vincristin
CH636883A5 (de)	1983-06-30	Verfahren zur herstellung von alkaloiden vom leurosin-typ.
DE2757858C2 (da)	1989-09-14
CH619465A5 (da)	1980-09-30
CH638516A5 (en)	1983-09-30	Process for preparing substituted aminoquinazoline derivatives
DE69427978T2 (de)	2001-11-29	Zwischenprodukt zur verwendung in der synthese und verfahren zur herstellung eines aminopiperazinderivates
CH634555A5 (de)	1983-02-15	Verfahren zur herstellung von mit nocardicin verwandten azetidinonen.
DE3024304C2 (da)	1991-10-31
EP0136662B1 (de)	1987-11-25	2,6-Dioxa-Bicyclo-[2,2,2]-octan-7-yl-acetaldehyde
DE2221808A1 (de)	1972-11-16	Verfahren zur Herstellung neuer heterocyclischer Verbindungen
DD143618A5 (de)	1980-09-03	Verfahren zur herstellung von dimeren vincaalkaloiden
DE2940737C2 (da)	1988-12-15
WO2003068779A1 (de)	2003-08-21	Cyclische verbindungen und ihre verwendung als komplexliganden
EP0117467A1 (de)	1984-09-05	Polyzyklische Bisamidine, Verfahren zu ihrer Herstellung und ihre Verwendung als Chemotherapeutika
DE3707530A1 (de)	1987-09-17	Neue substituierte dihalogenpyridine und verfahren zu ihrer herstellung sowie ihre weitere umsetzung zu pyridindicarbonsaeurediestern
DD146460A1 (de)	1981-02-11	Verfahren zur herstellung 1-benzylierter ergometrinderivate