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WO1996040667B1 - Paclitaxel synthesis from precursor compounds and methods of producing the same - Google Patents

Paclitaxel synthesis from precursor compounds and methods of producing the same

Info

Publication number
WO1996040667B1
WO1996040667B1 PCT/US1996/010228 US9610228W WO9640667B1 WO 1996040667 B1 WO1996040667 B1 WO 1996040667B1 US 9610228 W US9610228 W US 9610228W WO 9640667 B1 WO9640667 B1 WO 9640667B1
Authority
WO
WIPO (PCT)
Prior art keywords
deprotecting
side chain
acylating
protecting group
replace
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.)
Ceased
Application number
PCT/US1996/010228
Other languages
French (fr)
Other versions
WO1996040667A1 (en
Filing date
Publication date
Priority claimed from US08/483,084 external-priority patent/US5675025A/en
Application filed filed Critical
Priority to EA199800031A priority Critical patent/EA000436B1/en
Priority to EP96918485A priority patent/EP0832080B9/en
Priority to AU61131/96A priority patent/AU706406B2/en
Priority to DE69617425T priority patent/DE69617425T2/en
Priority to JP9502252A priority patent/JPH11513978A/en
Priority to AT96918485T priority patent/ATE209640T1/en
Publication of WO1996040667A1 publication Critical patent/WO1996040667A1/en
Publication of WO1996040667B1 publication Critical patent/WO1996040667B1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Abstract

A semi-synthesis of taxol using a protected baccatin III backbone which is esterified with a suitably protected side chain acid.

Claims

AMENDED CLAIMS[received by the International Bureau on 11 November 1996 (11.11.96); original claim 1 amended; remaining claims unchanged (1 page)]
1. A process of producing paclitaxel from an intermediate compound having the general formula:
Formula (a)
Figure imgf000003_0001
wherein Pχ is a hydrogenatable benzyl protecting group comprising the steps of deprotecting and acylating the intermediate compound at the nitrogen position of the A-ring side chain to replace the CBZ protecting group with PhCO, deprotecting the side chain at the C-2' position to replace Pχ with H and deprotecting at C-7 to replace the TES protecting group with H.
2. The process of claim 1 wherein the step of deprotecting at C-7 occurs before the removal of the hydrogenatable C-2' benzyl protecting group.
3. The process of claim 2 wherein the step of deprotecting and acylating the side chain nitrogen occurs before the step of deprotecting at C-7.
4. The process of claim 2 wherein the step of deprotecting at C-7 occurs before the step of deprotecting and acylating the side chain nitrogen.
5. The process of claim 1 wherein the step of deprotecting and acylating the side chain nitrogen is accomplished by dissolving the compound of Formula (a) in isopropanol and thereafter adding Pearlman's catalyst under a hydrogen atmosphere for a first interval of time to form a first mixture and thereafter reducing said first mixture to residue and taking up said residue in a solvent, adding a tertiary amine base and thereafter adding benzoyl chloride.
6. The process of claim 5 wherein said solvent is selected from a group consisting of ethyl acetate and toluene.
7. The process of claim 5 wherein the tertiary amine base is triethylamine.
PCT/US1996/010228 1995-06-07 1996-06-07 Paclitaxel synthesis from precursor compounds and methods of producing the same Ceased WO1996040667A1 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EA199800031A EA000436B1 (en) 1995-06-07 1996-06-07 A process of producing paclitaxel
EP96918485A EP0832080B9 (en) 1995-06-07 1996-06-07 Paclitaxel synthesis from precursor compounds and methods of producing the same
AU61131/96A AU706406B2 (en) 1995-06-07 1996-06-07 Paclitaxel synthesis from precursor compounds and methods of producing the same
DE69617425T DE69617425T2 (en) 1995-06-07 1996-06-07 PACLITAXEL SYNTHESIS FROM PRECURSOR CONNECTIONS AND METHOD FOR THE PRODUCTION THEREOF
JP9502252A JPH11513978A (en) 1995-06-07 1996-06-07 Synthesis of paclitaxel from its precursor compound and method for its production
AT96918485T ATE209640T1 (en) 1995-06-07 1996-06-07 PACLITAXEL SYNTHESIS FROM PRECURSOR COMPOUNDS AND METHOD FOR THE PRODUCTION THEREOF

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US08/483,084 US5675025A (en) 1995-06-07 1995-06-07 Paclitaxel synthesis from precursor compounds and methods of producing the same
US08/483,084 1995-06-07

Publications (2)

Publication Number Publication Date
WO1996040667A1 WO1996040667A1 (en) 1996-12-19
WO1996040667B1 true WO1996040667B1 (en) 1997-01-30

Family

ID=23918590

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/010228 Ceased WO1996040667A1 (en) 1995-06-07 1996-06-07 Paclitaxel synthesis from precursor compounds and methods of producing the same

Country Status (10)

Country Link
US (1) US5675025A (en)
EP (1) EP0832080B9 (en)
JP (1) JPH11513978A (en)
AT (1) ATE209640T1 (en)
AU (1) AU706406B2 (en)
CA (1) CA2222989A1 (en)
DE (1) DE69617425T2 (en)
EA (1) EA000436B1 (en)
GE (1) GEP19991748B (en)
WO (1) WO1996040667A1 (en)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100225535B1 (en) * 1996-08-27 1999-10-15 정지석 Manufacturing method of paclitaxel
AU739303B2 (en) 1997-08-21 2001-10-11 Florida State University Method for the synthesis of taxanes
US6150537A (en) * 1997-12-12 2000-11-21 Emory University Methods for the esterification of alcohols and compounds useful therefor as potential anticancer agents
US6048990A (en) * 1998-05-01 2000-04-11 Napro Biotherapeutics, Inc. Method for selective acylation of C-2'-O-protected-10-hydroxy-taxol at the C-10 position
KR20010043230A (en) 1998-05-01 2001-05-25 패트리샤 에이, 필리어 Methods and useful intermediates for paclitaxel synthesis from c-7, c-10 di-cbz baccatin iii
US6066749A (en) * 1998-05-01 2000-05-23 Napro Biotherapeutics, Inc. Method for conversion of C-2'-O-protected-10-hydroxy taxol to c-2'-O-protected taxol:useful intermediates in paclitaxel synthesis
US6002025A (en) * 1999-02-24 1999-12-14 Bcm Developement Inc. Method for the purification of taxanes
US6136999A (en) * 1999-06-21 2000-10-24 Napro Biotherapeutics, Inc. C-2 hydroxyl protected-n-acyl (2R,3S)-3-phenylisoserine substituted phenyl activated esters and method for production thereof
US6143902A (en) * 1999-06-21 2000-11-07 Napro Biotherapeutics, Inc. C-2 hydroxyl protected-N-acyl (2R,3S)-3-phenylisoserine N-imido activated esters and method for production thereof
US6452024B1 (en) 2000-02-22 2002-09-17 Chaichem Pharmaceuticals International Process for extraction and purification of paclitaxel from natural sources
US6358996B1 (en) 2000-06-09 2002-03-19 Napro Biotherapeutics, Inc. Stable isotope labeling of paclitaxel
AU2002254400B2 (en) * 2001-03-23 2007-08-09 Napro Biotherapeutics, Inc. Molecular conjugates for use in treatment of cancer
US6452025B1 (en) * 2001-04-25 2002-09-17 Napro Biotherapeutics, Inc. Three-step conversion of protected taxane ester to paclitaxel
US6653501B2 (en) 2001-06-27 2003-11-25 Napro Biotherapeutics, Inc. Chiral resolution method for producing compounds useful in the synthesis of taxanes
US7981928B2 (en) 2002-09-05 2011-07-19 Nanodynamics, Inc. Chemotherapy method using x-rays
WO2004068930A2 (en) * 2003-02-04 2004-08-19 Natural Pharmaceuticals Inc. Method and composition for preparing a compound using a benzolating agent essentially free of ring chlorination
US6759539B1 (en) 2003-02-27 2004-07-06 Chaichem Pharmaceuticals International Process for isolation and purification of paclitaxel from natural sources

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2601676B1 (en) * 1986-07-17 1988-09-23 Rhone Poulenc Sante PROCESS FOR THE PREPARATION OF TAXOL AND DESACETYL-10 TAXOL
FR2629819B1 (en) * 1988-04-06 1990-11-16 Rhone Poulenc Sante PROCESS FOR THE PREPARATION OF BACCATIN III AND DESACETYL-10 BACCATIN III DERIVATIVES
FR2629818B1 (en) * 1988-04-06 1990-11-16 Centre Nat Rech Scient PROCESS FOR THE PREPARATION OF 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
US5136060A (en) * 1989-11-14 1992-08-04 Florida State University Method for preparation of taxol using an oxazinone
FR2658513B1 (en) * 1990-02-21 1994-02-04 Rhone Poulenc Sante PROCESS FOR THE PREPARATION OF CIS-BETA-PHENYLGLYCIDIC- (2R, 3R) ACID.
FR2680506B1 (en) * 1991-08-19 1994-09-02 Rhone Poulenc Rorer Sa PROCESS FOR THE PREPARATION OF BETA-PHENYLISOSERIN DERIVATIVES AND THEIR USE.
FR2687150B1 (en) * 1992-02-07 1995-04-28 Rhone Poulenc Rorer Sa PROCESS FOR THE PREPARATION OF TAXANE DERIVATIVES.

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