DE69630230T2 - Paclitaxelsynthese aus vorläufervebindungen und verfahren zu deren herstellung - Google Patents
Paclitaxelsynthese aus vorläufervebindungen und verfahren zu deren herstellung Download PDFInfo
- Publication number
- DE69630230T2 DE69630230T2 DE69630230T DE69630230T DE69630230T2 DE 69630230 T2 DE69630230 T2 DE 69630230T2 DE 69630230 T DE69630230 T DE 69630230T DE 69630230 T DE69630230 T DE 69630230T DE 69630230 T2 DE69630230 T2 DE 69630230T2
- Authority
- DE
- Germany
- Prior art keywords
- protected
- formula
- paclitaxel
- taxol
- baccatin iii
- Prior art date
- 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 - Fee Related
Links
- 229930012538 Paclitaxel Natural products 0.000 title claims abstract description 48
- 229960001592 paclitaxel Drugs 0.000 title claims abstract description 48
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 title claims abstract description 48
- 238000000034 method Methods 0.000 title claims abstract description 17
- 238000003786 synthesis reaction Methods 0.000 title abstract description 10
- 230000015572 biosynthetic process Effects 0.000 title abstract description 9
- 238000004519 manufacturing process Methods 0.000 title description 10
- 239000002243 precursor Substances 0.000 title description 4
- OVMSOCFBDVBLFW-VHLOTGQHSA-N 5beta,20-epoxy-1,7beta,13alpha-trihydroxy-9-oxotax-11-ene-2alpha,4alpha,10beta-triyl 4,10-diacetate 2-benzoate Chemical compound O([C@@H]1[C@@]2(C[C@H](O)C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)O)C(=O)C1=CC=CC=C1 OVMSOCFBDVBLFW-VHLOTGQHSA-N 0.000 claims abstract description 58
- 229930014667 baccatin III Natural products 0.000 claims abstract description 29
- 150000001875 compounds Chemical class 0.000 claims description 25
- 125000006239 protecting group Chemical group 0.000 claims description 21
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- -1 benzyloxymethyl Chemical group 0.000 claims description 15
- 238000009833 condensation Methods 0.000 claims description 15
- 230000005494 condensation Effects 0.000 claims description 15
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 claims description 8
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 claims description 7
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 claims description 7
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 150000001718 carbodiimides Chemical class 0.000 claims 2
- 239000000543 intermediate Substances 0.000 abstract description 10
- RZARFIRJROUVLM-UHFFFAOYSA-N 3-azaniumyl-2-hydroxy-3-phenylpropanoate Chemical class OC(=O)C(O)C(N)C1=CC=CC=C1 RZARFIRJROUVLM-UHFFFAOYSA-N 0.000 abstract description 4
- 238000005917 acylation reaction Methods 0.000 abstract description 4
- 230000032050 esterification Effects 0.000 abstract description 4
- 238000005886 esterification reaction Methods 0.000 abstract description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N DL-isoserine Natural products NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 abstract 2
- 238000005222 photoaffinity labeling Methods 0.000 abstract 1
- 125000002456 taxol group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- 238000006243 chemical reaction Methods 0.000 description 34
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 28
- 230000002829 reductive effect Effects 0.000 description 25
- YWLXLRUDGLRYDR-ZHPRIASZSA-N 5beta,20-epoxy-1,7beta,10beta,13alpha-tetrahydroxy-9-oxotax-11-ene-2alpha,4alpha-diyl 4-acetate 2-benzoate Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](O)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 YWLXLRUDGLRYDR-ZHPRIASZSA-N 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- PIYPODQNLLWXJG-UHFFFAOYSA-N ethyl 3-amino-2-hydroxy-3-phenylpropanoate Chemical compound CCOC(=O)C(O)C(N)C1=CC=CC=C1 PIYPODQNLLWXJG-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 0 *C(*)[C@@](*[N+]([O-])OCc1ccccc1)c1ccccc1 Chemical compound *C(*)[C@@](*[N+]([O-])OCc1ccccc1)c1ccccc1 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- 125000003834 baccatin III group Chemical group 0.000 description 4
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical class BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 4
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- LADPCMZCENPFGV-UHFFFAOYSA-N chloromethoxymethylbenzene Chemical compound ClCOCC1=CC=CC=C1 LADPCMZCENPFGV-UHFFFAOYSA-N 0.000 description 3
- 239000007859 condensation product Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- RZARFIRJROUVLM-JGVFFNPUSA-N (2r,3s)-3-azaniumyl-2-hydroxy-3-phenylpropanoate Chemical group [O-]C(=O)[C@H](O)[C@@H]([NH3+])C1=CC=CC=C1 RZARFIRJROUVLM-JGVFFNPUSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229940123237 Taxane Drugs 0.000 description 2
- 241001116500 Taxus Species 0.000 description 2
- 241001116498 Taxus baccata Species 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 2
- JLEHSYHLHLHPAL-UHFFFAOYSA-N tert-butylurea Chemical compound CC(C)(C)NC(N)=O JLEHSYHLHLHPAL-UHFFFAOYSA-N 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- 125000003241 10-deacetylbaccatin III group Chemical group 0.000 description 1
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 1
- DLACRDONFBNRSP-KWIOUIIFSA-N 3'-N-debenzoyltaxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](N)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 DLACRDONFBNRSP-KWIOUIIFSA-N 0.000 description 1
- XXKYTTAVNYTVFC-UHFFFAOYSA-N 4-azidobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(N=[N+]=[N-])C=C1 XXKYTTAVNYTVFC-UHFFFAOYSA-N 0.000 description 1
- 229930190007 Baccatin Natural products 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- XXKYTTAVNYTVFC-PZFLKRBQSA-N N(=[N+]=[N-])C1=C(C=C(C(=O)Cl)C=C1[3H])[3H] Chemical compound N(=[N+]=[N-])C1=C(C=C(C(=O)Cl)C=C1[3H])[3H] XXKYTTAVNYTVFC-PZFLKRBQSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 241001620634 Roger Species 0.000 description 1
- 241001116495 Taxaceae Species 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000000719 anti-leukaemic effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 150000001942 cyclopropanes Chemical class 0.000 description 1
- UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
- 150000004141 diterpene derivatives Chemical class 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- HZDKMGNFWBZGEY-DLBZAZTESA-N ethyl (2r,3s)-2-hydroxy-3-phenyl-3-(phenylmethoxycarbonylamino)propanoate Chemical compound N([C@H]([C@@H](O)C(=O)OCC)C=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 HZDKMGNFWBZGEY-DLBZAZTESA-N 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- RCINICONZNJXQF-XAZOAEDWSA-N taxol® Chemical class O([C@@H]1[C@@]2(CC(C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3(C21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-XAZOAEDWSA-N 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Epoxy Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/483,082 US5948919A (en) | 1993-02-05 | 1995-06-07 | Paclitaxel synthesis from precursor compounds and methods of producing the same |
| US483082 | 1995-06-07 | ||
| PCT/US1996/010024 WO1996040666A1 (en) | 1995-06-07 | 1996-06-07 | Paclitaxel synthesis from precursor compounds and methods of producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69630230D1 DE69630230D1 (de) | 2003-11-06 |
| DE69630230T2 true DE69630230T2 (de) | 2004-07-29 |
Family
ID=23918577
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69630230T Expired - Fee Related DE69630230T2 (de) | 1995-06-07 | 1996-06-07 | Paclitaxelsynthese aus vorläufervebindungen und verfahren zu deren herstellung |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US5948919A (https=) |
| EP (1) | EP0847393B1 (https=) |
| JP (1) | JP2001501578A (https=) |
| AT (1) | ATE251147T1 (https=) |
| AU (1) | AU706872B2 (https=) |
| CA (1) | CA2222919A1 (https=) |
| DE (1) | DE69630230T2 (https=) |
| EA (1) | EA000678B1 (https=) |
| GE (1) | GEP19991873B (https=) |
| WO (1) | WO1996040666A1 (https=) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100225535B1 (ko) * | 1996-08-27 | 1999-10-15 | 정지석 | 파클리탁셀의 제조방법 |
| US5750737A (en) * | 1996-09-25 | 1998-05-12 | Sisti; Nicholas J. | Method for paclitaxel synthesis |
| US7288665B1 (en) * | 1997-08-18 | 2007-10-30 | Florida State University | Process for selective derivatization of taxanes |
| US7167711B1 (en) | 1997-12-23 | 2007-01-23 | Openwave Systems Inc. | System and method for controlling financial transactions over a wireless network |
| KR20010043230A (ko) | 1998-05-01 | 2001-05-25 | 패트리샤 에이, 필리어 | Ｃ-7, ｃ-10 디-ｃｂｚ 박카틴 ｉｉｉ로부터 파클리탁셀을제조하는 방법 및 이를 제조하는데 사용하기 위한 중간체 |
| JP2003502401A (ja) * | 1999-06-21 | 2003-01-21 | ナプロ バイオセラピューティクス，インコーポレイテッド | Ｃ−２ヒドロキシル保護−ｎ−アシル（２ｒ，３ｓ）−３−フェニルイソセリン活性化エステルおよびそれらの製造方法 |
| JP4502338B2 (ja) * | 1999-09-17 | 2010-07-14 | 株式会社横浜国際バイオ研究所 | タキソイド化合物の製造法 |
| US6414015B1 (en) | 2000-01-28 | 2002-07-02 | Utah State University | Laulimalide microtubule stabilizing agents |
| US6358996B1 (en) | 2000-06-09 | 2002-03-19 | Napro Biotherapeutics, Inc. | Stable isotope labeling of paclitaxel |
| CA2441484A1 (en) * | 2001-03-23 | 2002-10-03 | Napro Biotherapeutics, Inc. | Molecular conjugates for use in treatment of cancer |
| US6653501B2 (en) | 2001-06-27 | 2003-11-25 | Napro Biotherapeutics, Inc. | Chiral resolution method for producing compounds useful in the synthesis of taxanes |
| BRPI0511109A (pt) * | 2004-05-14 | 2007-11-27 | Immunogen Inc | método fácil para sintetizar compostos de baccatin iii |
| CN102584632A (zh) * | 2011-09-28 | 2012-07-18 | 北京东方协和医药生物技术有限公司 | 一种多西他赛手性侧链中间体的制备方法 |
| HK1213740A1 (zh) * | 2013-03-15 | 2016-07-15 | Inspyr Therapeutics, Inc. | 制备抗癌症组合物的方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2601676B1 (fr) * | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | Procede de preparation du taxol et du desacetyl-10 taxol |
| FR2629819B1 (fr) * | 1988-04-06 | 1990-11-16 | Rhone Poulenc Sante | Procede de preparation de derives de la baccatine iii et de la desacetyl-10 baccatine iii |
| FR2629818B1 (fr) * | 1988-04-06 | 1990-11-16 | Centre Nat Rech Scient | Procede de preparation du taxol |
| US5175315A (en) * | 1989-05-31 | 1992-12-29 | Florida State University | Method for preparation of taxol using β-lactam |
| US5015744A (en) * | 1989-11-14 | 1991-05-14 | Florida State University | Method for preparation of taxol using an oxazinone |
| US5399726A (en) * | 1993-01-29 | 1995-03-21 | Florida State University | Process for the preparation of baccatin III analogs bearing new C2 and C4 functional groups |
| FR2687150B1 (fr) * | 1992-02-07 | 1995-04-28 | Rhone Poulenc Rorer Sa | Procede de preparation de derives du taxane. |
-
1995
- 1995-06-07 US US08/483,082 patent/US5948919A/en not_active Expired - Fee Related
-
1996
- 1996-06-07 JP JP09502161A patent/JP2001501578A/ja not_active Ceased
- 1996-06-07 WO PCT/US1996/010024 patent/WO1996040666A1/en not_active Ceased
- 1996-06-07 EP EP96919348A patent/EP0847393B1/en not_active Expired - Lifetime
- 1996-06-07 DE DE69630230T patent/DE69630230T2/de not_active Expired - Fee Related
- 1996-06-07 EA EA199800024A patent/EA000678B1/ru not_active IP Right Cessation
- 1996-06-07 GE GEAP19964065A patent/GEP19991873B/en unknown
- 1996-06-07 AU AU61706/96A patent/AU706872B2/en not_active Ceased
- 1996-06-07 AT AT96919348T patent/ATE251147T1/de not_active IP Right Cessation
- 1996-06-07 CA CA002222919A patent/CA2222919A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2001501578A (ja) | 2001-02-06 |
| EA199800024A1 (ru) | 1998-06-25 |
| AU6170696A (en) | 1996-12-30 |
| DE69630230D1 (de) | 2003-11-06 |
| AU706872B2 (en) | 1999-06-24 |
| US5948919A (en) | 1999-09-07 |
| EP0847393A4 (https=) | 1998-07-08 |
| ATE251147T1 (de) | 2003-10-15 |
| WO1996040666A1 (en) | 1996-12-19 |
| EP0847393A1 (en) | 1998-06-17 |
| CA2222919A1 (en) | 1996-12-19 |
| EA000678B1 (ru) | 2000-02-28 |
| GEP19991873B (en) | 1999-12-06 |
| EP0847393B1 (en) | 2003-10-01 |
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| 8339 | Ceased/non-payment of the annual fee |