BG61074B2 - Метод за получаване на таксол - Google Patents

Метод за получаване на таксол Download PDF

Info

Publication number: BG61074B2
Authority: BG; Bulgaria
Prior art keywords: aryl; taxol; alkyl; alkenyl; alkynyl
Prior art date: 1989-05-31

Application number

BG092102A

Other languages

Bulgarian (bg)

English (en)

Inventor

Robert Holton

Original Assignee

Florida State University

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.)

1989-05-31

Filing date

1990-05-30

Publication date

1996-10-31

1990-05-30 Application filed by Florida State University filed Critical Florida State University

1990-05-30 Priority claimed from DD341149A external-priority patent/DD300428A5/de

1996-10-31 Publication of BG61074B2 publication Critical patent/BG61074B2/bg

Links

229930012538 Paclitaxel Natural products 0.000 title claims abstract description 53
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 53
229960001592 paclitaxel Drugs 0.000 title claims abstract description 52
238000000034 method Methods 0.000 title claims abstract description 34
125000003118 aryl group Chemical group 0.000 claims abstract description 34
125000003342 alkenyl group Chemical group 0.000 claims abstract description 28
125000000217 alkyl group Chemical group 0.000 claims abstract description 28
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 25
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
239000001257 hydrogen Substances 0.000 claims abstract description 24
125000000304 alkynyl group Chemical group 0.000 claims abstract description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 21
125000003107 substituted aryl group Chemical group 0.000 claims abstract description 20
238000002360 preparation method Methods 0.000 claims abstract description 18
125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims abstract description 13
239000012190 activator Substances 0.000 claims abstract description 11
125000006239 protecting group Chemical group 0.000 claims abstract description 8
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 6
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Chemical group CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims abstract description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
150000003952 β-lactams Chemical class 0.000 claims description 35
-1 2,2,2-trichloroethoxymethyl Chemical group 0.000 claims description 29
125000004423 acyloxy group Chemical group 0.000 claims description 23
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 18
230000015572 biosynthetic process Effects 0.000 claims description 17
125000001424 substituent group Chemical group 0.000 claims description 17
238000003786 synthesis reaction Methods 0.000 claims description 17
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
150000002431 hydrogen Chemical class 0.000 claims description 9
125000003302 alkenyloxy group Chemical group 0.000 claims description 8
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 6
238000006243 chemical reaction Methods 0.000 claims description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
150000002466 imines Chemical class 0.000 claims description 4
AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 3
150000004649 carbonic acid derivatives Chemical class 0.000 claims description 3
150000002148 esters Chemical class 0.000 claims description 3
150000002170 ethers Chemical class 0.000 claims description 3
150000003512 tertiary amines Chemical group 0.000 claims description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 claims 1
LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 claims 1
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims 1
150000001412 amines Chemical class 0.000 claims 1
XLSZMDLNRCVEIJ-UHFFFAOYSA-N methylimidazole Natural products CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 claims 1
125000002252 acyl group Chemical group 0.000 abstract description 4
230000001093 anti-cancer Effects 0.000 abstract description 2
239000002246 antineoplastic agent Substances 0.000 abstract 2
229940127089 cytotoxic agent Drugs 0.000 abstract 1
239000003814 drug Substances 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
239000000243 solution Substances 0.000 description 26
125000004432 carbon atom Chemical group C* 0.000 description 16
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
239000000203 mixture Substances 0.000 description 14
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 description 11
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 10
239000000543 intermediate Substances 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
229920006395 saturated elastomer Polymers 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
XSYLUBKWRZCOQP-QIWLAUOQSA-N (3s,4r)-1-benzoyl-3-(1-ethoxyethoxy)-4-phenylazetidin-2-one Chemical compound N1([C@@H]([C@@H](C1=O)OC(C)OCC)C=1C=CC=CC=1)C(=O)C1=CC=CC=C1 XSYLUBKWRZCOQP-QIWLAUOQSA-N 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
239000007787 solid Substances 0.000 description 6
239000000126 substance Substances 0.000 description 6
229930014667 baccatin III Natural products 0.000 description 5
150000001875 compounds Chemical class 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
239000013078 crystal Substances 0.000 description 4
FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 4
239000003921 oil Substances 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
FBZSDKXFQUKDLD-SFYZADRCSA-N (3s,4r)-3-hydroxy-4-phenylazetidin-2-one Chemical compound N1C(=O)[C@@H](O)[C@H]1C1=CC=CC=C1 FBZSDKXFQUKDLD-SFYZADRCSA-N 0.000 description 3
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
229940123237 Taxane Drugs 0.000 description 3
YWTCDTFWPNSBIU-SJORKVTESA-N [(3s,4r)-1-(4-methoxyphenyl)-2-oxo-4-phenylazetidin-3-yl] acetate Chemical compound C1=CC(OC)=CC=C1N1C(=O)[C@@H](OC(C)=O)[C@H]1C1=CC=CC=C1 YWTCDTFWPNSBIU-SJORKVTESA-N 0.000 description 3
YTBSMLRVFPHDOB-ZJUUUORDSA-N [(3s,4r)-2-oxo-4-phenylazetidin-3-yl] acetate Chemical compound N1C(=O)[C@@H](OC(=O)C)[C@H]1C1=CC=CC=C1 YTBSMLRVFPHDOB-ZJUUUORDSA-N 0.000 description 3
150000001241 acetals Chemical class 0.000 description 3
239000002253 acid Substances 0.000 description 3
230000000259 anti-tumor effect Effects 0.000 description 3
XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 3
239000010410 layer Substances 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
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 3
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
241001116500 Taxus Species 0.000 description 2
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
125000003368 amide group Chemical group 0.000 description 2
238000013459 approach Methods 0.000 description 2
229910052786 argon Inorganic materials 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
BSXPOWNLFFUVTE-UHFFFAOYSA-N benzyl 3-benzamido-2-hydroxy-3-phenylpropanoate Chemical compound C=1C=CC=CC=1COC(=O)C(O)C(C=1C=CC=CC=1)NC(=O)C1=CC=CC=C1 BSXPOWNLFFUVTE-UHFFFAOYSA-N 0.000 description 2
125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 2
125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
239000002024 ethyl acetate extract Substances 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
125000006038 hexenyl group Chemical group 0.000 description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000005980 hexynyl group Chemical group 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
229930014626 natural product Natural products 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 2
239000000047 product Substances 0.000 description 2
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000010189 synthetic method Methods 0.000 description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
HZDNNJABYXNPPV-UHFFFAOYSA-N (2-chloro-2-oxoethyl) acetate Chemical compound CC(=O)OCC(Cl)=O HZDNNJABYXNPPV-UHFFFAOYSA-N 0.000 description 1
XSYLUBKWRZCOQP-UHFFFAOYSA-N 1-benzoyl-3-(1-ethoxyethoxy)-4-phenylazetidin-2-one Chemical compound O=C1C(OC(C)OCC)C(C=2C=CC=CC=2)N1C(=O)C1=CC=CC=C1 XSYLUBKWRZCOQP-UHFFFAOYSA-N 0.000 description 1
WFCHQDPYEFIAQO-UHFFFAOYSA-N 1-benzoyl-4-phenyl-3-(2,2,2-trichloroethoxymethoxy)azetidin-2-one Chemical compound O=C1C(OCOCC(Cl)(Cl)Cl)C(C=2C=CC=CC=2)N1C(=O)C1=CC=CC=C1 WFCHQDPYEFIAQO-UHFFFAOYSA-N 0.000 description 1
GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
LUYQINUDJUXWNB-UHFFFAOYSA-N 3-(1-ethoxyethoxy)-4-phenylazetidin-2-one Chemical compound N1C(=O)C(OC(C)OCC)C1C1=CC=CC=C1 LUYQINUDJUXWNB-UHFFFAOYSA-N 0.000 description 1
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
229930190007 Baccatin Natural products 0.000 description 1
101150065749 Churc1 gene Proteins 0.000 description 1
239000004593 Epoxy Substances 0.000 description 1
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
102100038239 Protein Churchill Human genes 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
241001116498 Taxus baccata Species 0.000 description 1
235000009065 Taxus cuspidata Nutrition 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
238000007259 addition reaction Methods 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
229920000180 alkyd Polymers 0.000 description 1
230000000719 anti-leukaemic effect Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
230000000973 chemotherapeutic effect Effects 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
229910000365 copper sulfate Inorganic materials 0.000 description 1
ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
150000002118 epoxides Chemical class 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
238000005304 joining Methods 0.000 description 1
150000003951 lactams Chemical class 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
125000005911 methyl carbonate group Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
125000003566 oxetanyl group Chemical group 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
150000004579 taxol derivatives Chemical class 0.000 description 1
125000002456 taxol group Chemical group 0.000 description 1
150000003505 terpenes Chemical class 0.000 description 1
235000007586 terpenes Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
- 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
- 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

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Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Oncology (AREA)
Hematology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Epoxy Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Medicinal Preparation (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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BG092102A 1989-05-31 1990-05-30 Метод за получаване на таксол BG61074B2 (bg)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US35963489A	1989-05-31	1989-05-31
US07/415,028 US5175315A (en)	1989-05-31	1989-09-29	Method for preparation of taxol using β-lactam
DD341149A DD300428A5 (de)	1989-05-31	1990-05-30	Verfahren zur herstellung von taxol

Publications (1)

Publication Number	Publication Date
BG61074B2 true BG61074B2 (bg)	1996-10-31

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BG092102A BG61074B2 (bg)	1989-05-31	1990-05-30	Метод за получаване на таксол

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EP (1)	EP0400971B1 (xx)
JP (2)	JPH0830050B2 (xx)
KR (1)	KR0130387B1 (xx)
CN (2)	CN1057082C (xx)
AT (1)	ATE168997T1 (xx)
AU (1)	AU630696B2 (xx)
BG (1)	BG61074B2 (xx)
CA (2)	CA2214051C (xx)
DE (1)	DE69032512T2 (xx)
DK (1)	DK0400971T3 (xx)
EG (1)	EG19555A (xx)
ES (1)	ES2122957T3 (xx)
FI (1)	FI102176B (xx)
HU (1)	HU208003B (xx)
IE (1)	IE62678B1 (xx)
IL (1)	IL94426A (xx)
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NO (1)	NO174099C (xx)
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OA (1)	OA09740A (xx)
PL (2)	PL163946B1 (xx)
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RO (1)	RO111766B1 (xx)
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SG (1)	SG43234A1 (xx)
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ZA (1)	ZA903809B (xx)

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1989
- 1989-09-29 US US07/415,028 patent/US5175315A/en not_active Expired - Lifetime
1990
- 1990-05-11 IE IE170790A patent/IE62678B1/en not_active IP Right Cessation
- 1990-05-14 NZ NZ233663A patent/NZ233663A/en unknown
- 1990-05-16 CA CA002214051A patent/CA2214051C/en not_active Expired - Lifetime
- 1990-05-16 CA CA002016951A patent/CA2016951C/en not_active Expired - Lifetime
- 1990-05-17 ZA ZA903809A patent/ZA903809B/xx unknown
- 1990-05-17 IL IL94426A patent/IL94426A/en not_active IP Right Cessation
- 1990-05-18 AU AU55150/90A patent/AU630696B2/en not_active Expired
- 1990-05-18 YU YU00975/90A patent/YU97590A/xx unknown
- 1990-05-29 PT PT94187A patent/PT94187B/pt not_active IP Right Cessation
- 1990-05-29 HU HU903245A patent/HU208003B/hu unknown
- 1990-05-29 FI FI902660A patent/FI102176B/fi active IP Right Grant
- 1990-05-29 RU SU904830122A patent/RU2097374C1/ru not_active IP Right Cessation
- 1990-05-30 JP JP2141225A patent/JPH0830050B2/ja not_active Expired - Fee Related
- 1990-05-30 DK DK90305845T patent/DK0400971T3/da active
- 1990-05-30 SG SG1996005969A patent/SG43234A1/en unknown
- 1990-05-30 DE DE69032512T patent/DE69032512T2/de not_active Expired - Lifetime
- 1990-05-30 PL PL90285404A patent/PL163946B1/pl unknown
- 1990-05-30 EG EG31890A patent/EG19555A/xx active
- 1990-05-30 EP EP90305845A patent/EP0400971B1/en not_active Expired - Lifetime
- 1990-05-30 BG BG092102A patent/BG61074B2/bg unknown
- 1990-05-30 AT AT90305845T patent/ATE168997T1/de not_active IP Right Cessation
- 1990-05-30 NO NO902404A patent/NO174099C/no not_active IP Right Cessation
- 1990-05-30 ES ES90305845T patent/ES2122957T3/es not_active Expired - Lifetime
- 1990-05-30 CN CN90103963A patent/CN1057082C/zh not_active Expired - Lifetime
- 1990-05-30 PL PL90300114A patent/PL164539B1/pl unknown
- 1990-05-31 OA OA59797A patent/OA09740A/en unknown
- 1990-06-12 RO RO145328A patent/RO111766B1/ro unknown
1992
- 1992-06-25 MX MX9203429A patent/MX9203429A/es unknown
1993
- 1993-04-05 CN CN931036623A patent/CN1064958C/zh not_active Expired - Lifetime
1994
- 1994-07-28 JP JP6176360A patent/JP2500198B2/ja not_active Expired - Fee Related
1997
- 1997-07-09 KR KR1019970031738A patent/KR0130387B1/ko not_active IP Right Cessation

Also Published As

Publication number	Publication date
CA2016951C (en)	1998-05-12
AU630696B2 (en)	1992-11-05
FI102176B1 (fi)	1998-10-30
MX9203429A (es)	1992-07-01
PT94187A (pt)	1991-02-08
CN1057049A (zh)	1991-12-18
ATE168997T1 (de)	1998-08-15
OA09740A (en)	1993-11-30
US5175315A (en)	1992-12-29
NO902404L (no)	1990-12-03
IL94426A (en)	1998-06-15
CA2214051A1 (en)	1990-11-30
CA2214051C (en)	2001-09-25
RO111766B1 (ro)	1997-01-30
DE69032512D1 (de)	1998-09-03
JPH0386860A (ja)	1991-04-11
EP0400971B1 (en)	1998-07-29
ES2122957T3 (es)	1999-01-01
CN1057082C (zh)	2000-10-04
PT94187B (pt)	1996-08-30
DE69032512T2 (de)	1999-03-25
HU903245D0 (en)	1990-10-28
FI902660A0 (fi)	1990-05-29
PL164539B1 (pl)	1994-08-31
EP0400971A3 (en)	1992-01-02
CN1064958C (zh)	2001-04-25
DK0400971T3 (da)	1999-04-26
SG43234A1 (en)	1997-10-17
NO174099C (no)	1994-03-16
PL285404A1 (en)	1991-02-11
CN1086512A (zh)	1994-05-11
HU208003B (en)	1993-07-28
EP0400971A2 (en)	1990-12-05
CA2016951A1 (en)	1990-11-30
KR0130387B1 (ko)	1998-04-09
IE62678B1 (en)	1995-02-22
PL163946B1 (pl)	1994-05-31
ZA903809B (en)	1991-03-27
FI102176B (fi)	1998-10-30
IL94426A0 (en)	1991-03-10
NO174099B (no)	1993-12-06
HUT57199A (en)	1991-11-28
IE901707L (en)	1990-11-30
RU2097374C1 (ru)	1997-11-27
NO902404D0 (no)	1990-05-30
JP2500198B2 (ja)	1996-05-29
JPH0770057A (ja)	1995-03-14
YU97590A (en)	1991-10-31
AU5515090A (en)	1990-12-20
NZ233663A (en)	1992-09-25
JPH0830050B2 (ja)	1996-03-27
EG19555A (en)	1995-09-30

Publication	Publication Date	Title
US5574156A (en)	1996-11-12	β-lactams used in preparing taxol
BG61074B2 (bg)	1996-10-31	Метод за получаване на таксол
US5384399A (en)	1995-01-24	Oxazinone compounds for the preparation of taxol
US5015744A (en)	1991-05-14	Method for preparation of taxol using an oxazinone
RU2098413C1 (ru)	1997-12-10	Алкоголяты металлов
US5254703A (en)	1993-10-19	Semi-synthesis of taxane derivatives using metal alkoxides and oxazinones
JP2004043439A (ja)	2004-02-12	β−ラクタム
CZ287206B6 (cs)	2000-10-11	Způsob výroby derivátů taxolu a beta-laktam jako výchozí látka pro výrobu těchto derivátů
PL168497B1 (pl)	1996-02-29	Sposób wytwarzania taksolu