EP0923583A1 - Procede de fabrication d'epothilones, et composes intermediaires obtenus au cours de ce procede - Google Patents

Procede de fabrication d'epothilones, et composes intermediaires obtenus au cours de ce procede

Info

Publication number
EP0923583A1
EP0923583A1 EP97914077A EP97914077A EP0923583A1 EP 0923583 A1 EP0923583 A1 EP 0923583A1 EP 97914077 A EP97914077 A EP 97914077A EP 97914077 A EP97914077 A EP 97914077A EP 0923583 A1 EP0923583 A1 EP 0923583A1
Authority
EP
European Patent Office
Prior art keywords
mmol
solution
methyl
hydrogen
mixture
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.)
Withdrawn
Application number
EP97914077A
Other languages
German (de)
English (en)
Inventor
Dieter Schinzer
Anja Limberg
Oliver M. BÖHM
Armin Bauer
Martin Cordes
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novartis AG
Original Assignee
Novartis AG
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.)
Filing date
Publication date
Priority claimed from DE19636343A external-priority patent/DE19636343C1/de
Priority claimed from DE19645361A external-priority patent/DE19645361A1/de
Priority claimed from DE19645362A external-priority patent/DE19645362A1/de
Application filed by Novartis AG filed Critical Novartis AG
Publication of EP0923583A1 publication Critical patent/EP0923583A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/24—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
    • C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
    • 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
    • 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

Definitions

  • ERSATZBI_ATT (RULE 26) The invention thus relates to a process for the preparation of epitholone A or B of the general formula 1
  • reaction solution is then reduced to a quarter in vacuo. It is diluted with 130 ml of sat. NaCI solution and adjust to pH 4-5 with 1 M KHS04 solution. It is extracted with diethyl ether. The combined organic phases are dried over MgSO4 and the solvent is distilled off on a rotary evaporator. This gives 2.01 g (8.17 mmol) of 6 - [(terr-rutvlriimethvlsilvhoxvl-hexanoic acid, corresponding to a yield of 90%.
  • 2H26 ⁇ 3Si, FG 246.42 g / mol
  • Connection 5a is made analogously. From 238 mg (1.70 mmol) 3a, 386 mg (1.09 mmol, 64%) 5a are obtained.
  • Connection 6a is established analogously. 96 mg (0.270 mmol) 5a gives 77 mg (0.246 mmol, 91%) ⁇ a.
  • ERSATZB.LATT (RULE 26) (4S, 7H, 8S, 9S, 16S, 13Z) -4,8-di-fert-butyldim ⁇ thylsilyloxy-5 ⁇ 5,7,9-t ⁇ tra-methyl-16- [(£) -1-methyl-2- ( 2-methylthiazol-4-yl) vinyl] -1-oxa-cyclohexadec-13-ene-2,6-dione 18 and

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)

Abstract

La présente invention porte sur un procédé de fabrication d'épothilones et sur les composés intermédiaires obtenus au cours de ce procédé. Epothilone A et B sont des substances naturelles pouvant être fabriquées par les microorganismes et possédant des propriétés analogues au taxol, d'où l'intérêt qu'elles présentent pour la chimie pharmaceutique.
EP97914077A 1996-08-30 1997-01-15 Procede de fabrication d'epothilones, et composes intermediaires obtenus au cours de ce procede Withdrawn EP0923583A1 (fr)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
DE19636343A DE19636343C1 (de) 1996-08-30 1996-08-30 Zwischenprodukte innerhalb der Totalsynthese von Epothilon A und B
DE19636343 1996-08-30
DE19645361 1996-10-28
DE19645361A DE19645361A1 (de) 1996-08-30 1996-10-28 Zwischenprodukte innerhalb der Totalsynthese von Epothilon A und B, Teil II
DE19645362 1996-10-28
DE19645362A DE19645362A1 (de) 1996-10-28 1996-10-28 Verfahren zur Herstellung von Epothilon A und B und Derivaten
PCT/DE1997/000111 WO1998008849A1 (fr) 1996-08-30 1997-01-15 Procede de fabrication d'epothilones, et composes intermediaires obtenus au cours de ce procede

Publications (1)

Publication Number Publication Date
EP0923583A1 true EP0923583A1 (fr) 1999-06-23

Family

ID=27216622

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97914077A Withdrawn EP0923583A1 (fr) 1996-08-30 1997-01-15 Procede de fabrication d'epothilones, et composes intermediaires obtenus au cours de ce procede

Country Status (5)

Country Link
EP (1) EP0923583A1 (fr)
JP (1) JP2001500851A (fr)
AU (1) AU716610B2 (fr)
NZ (1) NZ334821A (fr)
WO (1) WO1998008849A1 (fr)

Families Citing this family (139)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE59609305D1 (de) 1995-11-17 2002-07-11 Biotechnolog Forschung Gmbh Epothilon-Derivate und deren Herstellung
WO1998022461A1 (fr) 1996-11-18 1998-05-28 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Epothilone c, d, e et f, mode de preparation et application comme agents cytostatiques et phytosanitaires
US6867305B2 (en) 1996-12-03 2005-03-15 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
JP4579351B2 (ja) 1996-12-03 2010-11-10 スローン−ケッタリング インスティトュート フォア キャンサー リサーチ エポチロンの合成とその中間体及びその類似物並びにその使用
US6204388B1 (en) 1996-12-03 2001-03-20 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
US6660758B1 (en) 1996-12-13 2003-12-09 The Scripps Research Institute Epothilone analogs
US6380394B1 (en) 1996-12-13 2002-04-30 The Scripps Research Institute Epothilone analogs
US6441186B1 (en) * 1996-12-13 2002-08-27 The Scripps Research Institute Epothilone analogs
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US6365749B1 (en) 1997-12-04 2002-04-02 Bristol-Myers Squibb Company Process for the preparation of ring-opened epothilone intermediates which are useful for the preparation of epothilone analogs
US6683100B2 (en) 1999-01-19 2004-01-27 Novartis Ag Organic compounds
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FR2775187B1 (fr) 1998-02-25 2003-02-21 Novartis Ag Utilisation de l'epothilone b pour la fabrication d'une preparation pharmaceutique antiproliferative et d'une composition comprenant l'epothilone b comme agent antiproliferatif in vivo
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AU2149397A (en) 1998-03-19
WO1998008849A1 (fr) 1998-03-05

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