DE69314239C5 - Verfahren zur Stereoselektivglycosylierung - Google Patents

Verfahren zur Stereoselektivglycosylierung Download PDF

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Publication number
DE69314239C5
DE69314239C5 DE69314239T DE69314239T DE69314239C5 DE 69314239 C5 DE69314239 C5 DE 69314239C5 DE 69314239 T DE69314239 T DE 69314239T DE 69314239 T DE69314239 T DE 69314239T DE 69314239 C5 DE69314239 C5 DE 69314239C5
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Prior art keywords
formula
group
compound
process according
nucleophilic
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Expired - Lifetime
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DE69314239T
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DE69314239D1 (de
DE69314239T2 (de
Inventor
Ta-Sen Chou
Laurie Michelle Poteet
Douglas Patton Kjell
Cora Sue Grossman
Larry Wayne Hertel
Richard Elmer Holmes
Charles David Jones
Thomas Edward Mabry
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Eli Lilly and Co
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Eli Lilly and Co
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Priority claimed from US07/902,312 external-priority patent/US5371210A/en
Priority claimed from US08/044,312 external-priority patent/US5426183A/en
Priority claimed from US08/044,345 external-priority patent/US5594124A/en
Priority claimed from US08/044,996 external-priority patent/US5821357A/en
Priority claimed from US08/044,343 external-priority patent/US5401838A/en
Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co
Publication of DE69314239D1 publication Critical patent/DE69314239D1/de
Publication of DE69314239T2 publication Critical patent/DE69314239T2/de
Publication of DE69314239C5 publication Critical patent/DE69314239C5/de
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Saccharide Compounds (AREA)
  • Steroid Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heat Sensitive Colour Forming Recording (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)

Abstract

Verfahren zur Synthese eines an β-Anomer angereicherten Nukleosids der Formelwelches, gegebenenfalls in einem geeigneten Lösungsmittel, das Durchführen einer nucleophilen SN2-Substitution einer Sulfonyloxy-Gruppe (Y) aus einem an α-Anomer angereicherten Kohlenhydrat der Formel...

Description

  • Der Bundesgerichtshof hat auf die mündliche Verhandlung vom 3. April 2012 für Recht erkannt:
    Das europäische Patent 577 303 wird dadurch teilweise für nichtig erklärt, dass die Patentansprüche folgende Fassung erhalten:

Claims (8)

  1. Verfahren zur Synthese eines an β-Anomer angereicherten Nukleosids der Formel
    Figure 00020001
    welches, gegebenenfalls in einem geeigneten Lösungsmittel, das Durchführen einer nucleophilen SN2-Substitution einer Sulfonyloxy-Gruppe (Y) aus einem an α-Anomer angereicherten Kohlenhydrat der Formel
    Figure 00020002
    umfasst, wobei X unabhängig ausgewählt ist unter Hydroxy-Schutzgruppen, mit mindestens einem Moläquivalent einer Nukleobase, ausgewählt aus der Gruppe bestehend aus
    Figure 00030001
    wobei R1 Wasserstoff, Z eine Hydroxy-Schutzgruppe, W eine Amino-Schutzgruppe und M+ ein Kation ist und R2 ausgewählt ist aus der Gruppe bestehend aus Azid, primärem Amin und sekundärem Amin, und Entfernen der Schutzgruppe unter Bildung der Verbindung der Formel (I).
  2. Verfahren nach Anspruch 1, wobei der Katalysator ausgewählt ist unter stark ionisierten Salzen, deren Anion nicht nukleophil ist und die im Lösungsmittel im Wesentlichen löslich sind.
  3. Verfahren nach Anspruch 1 oder 2, bei dem das Lösungsmittel ausgewählt ist unter polaren, nicht-nukleophilen Lösungsmitteln.
  4. Verfahren nach Anspruch 1, wobei die Reaktionstemperatur von etwa 100°C bis etwa 160°C beträgt.
  5. Verfahren nach einem der vorhergehenden Ansprüche zur Herstellung einer Verbindung der Formel (I), welche die folgende Struktur aufweist
    Figure 00030002
  6. Verfahren nach einem der vorhergehenden Ansprüche, wobei die Schutzgruppe (X) der Verbindung der Formel (II) Benzoyl ist.
  7. Verfahren nach einem der Ansprüche 1 bis 6, wobei die Sulfonyloxygruppe (Y) der Verbindung der Formel (II) Methansulfonyloxy ist.
  8. Verfahren nach einem der Ansprüche 1 bis 7, wobei die Sulfonyloxygruppe (Y) der Verbindung der Formel (II) Trifluormethansulfonyloxy ist.
DE69314239T 1992-06-22 1993-06-21 Verfahren zur Stereoselektivglycosylierung Expired - Lifetime DE69314239C5 (de)

Applications Claiming Priority (25)

Application Number Priority Date Filing Date Title
US90213592A 1992-06-22 1992-06-22
US90211292A 1992-06-22 1992-06-22
US90215092A 1992-06-22 1992-06-22
US90231392A 1992-06-22 1992-06-22
US90230292A 1992-06-22 1992-06-22
US902312 1992-06-22
US902135 1992-06-22
US902302 1992-06-22
US902313 1992-06-22
US902112 1992-06-22
US07/902,312 US5371210A (en) 1992-06-22 1992-06-22 Stereoselective fusion glycosylation process for preparing 2'-deoxy-2',2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides
US902150 1992-06-22
US4431593A 1993-04-07 1993-04-07
US4430993A 1993-04-07 1993-04-07
US08/044,345 US5594124A (en) 1992-06-22 1993-04-07 Stereoselective glycosylation process for preparing 2'-Deoxy-2',2'-difluoropyrimidine nucleosides and 2'-deoxy-2'-fluoropyrimidine nucleosides and intermediates thereof
US44315 1993-04-07
US44345 1993-04-07
US44309 1993-04-07
US08/044,996 US5821357A (en) 1992-06-22 1993-04-07 Stereoselective glycosylation process for preparing 2'-deoxy-2',2'-difluoropurine and triazole nucleosides
US44312 1993-04-07
US44996 1993-04-07
US44343 1993-04-07
US08/044,343 US5401838A (en) 1992-06-22 1993-04-07 Stereoselective fusion glycosylation process for preparing 2'-deoxy-2',2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides
US08/044,312 US5426183A (en) 1992-06-22 1993-04-07 Catalytic stereoselective glycosylation process for preparing 2'-deoxy-2',2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides
EP93304817A EP0577303B1 (de) 1992-06-22 1993-06-21 Verfahren zur Stereoselektivglycosylierung

Publications (3)

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DE69314239D1 DE69314239D1 (de) 1997-11-06
DE69314239T2 DE69314239T2 (de) 1998-02-19
DE69314239C5 true DE69314239C5 (de) 2012-11-29

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EP (1) EP0577303B1 (de)
JP (1) JP3313191B2 (de)
KR (1) KR100252452B1 (de)
AT (1) ATE158799T1 (de)
BR (1) BR9302434A (de)
CA (1) CA2098881C (de)
CY (1) CY2067A (de)
DE (1) DE69314239C5 (de)
DK (1) DK0577303T3 (de)
ES (1) ES2107624T3 (de)
FI (1) FI108643B (de)
GR (1) GR3025689T3 (de)
HU (2) HUT64358A (de)
IL (1) IL106071A (de)
MX (1) MX9303707A (de)
MY (1) MY115775A (de)
NO (1) NO180235B3 (de)
NZ (1) NZ247939A (de)
PL (1) PL172348B1 (de)
UA (1) UA41261C2 (de)

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AU1289697A (en) 1995-12-13 1997-07-03 Eli Lilly And Company Alpha, alpha-difluoro-beta-hydroxy thiol esters and their synthesis
US6326507B1 (en) 1998-06-19 2001-12-04 Trustees Of Dartmouth College Therapeutic compounds and methods of use
AU2001238516B2 (en) 2000-02-18 2005-08-04 Southern Research Institute Methods for synthesizing 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H- purin-6-amine
US7435755B2 (en) 2000-11-28 2008-10-14 The Trustees Of Dartmouth College CDDO-compounds and combination therapies thereof
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WO2004041203A2 (en) 2002-11-04 2004-05-21 Xenoport, Inc. Gemcitabine prodrugs, pharmaceutical compositions and uses thereof
JP4599295B2 (ja) * 2003-05-22 2010-12-15 独立行政法人科学技術振興機構 α−選択的グリコシル化反応方法
WO2006070985A1 (en) 2004-12-30 2006-07-06 Hanmi Pharm. Co., Ltd. METHOD FOR THE PREPARATION OF 2#-DEOXY-2#,2#-DIFLUOROCYTIDINE
KR20070112774A (ko) * 2005-03-04 2007-11-27 다브르 파마 리미티드 베타―아노머가 많은２１데옥시，２１，２１－디플루오로－ｄ－리보푸라노실뉴클레오시드의 제조를 위한 중간체 및 제조 방법
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CN100391966C (zh) * 2005-06-17 2008-06-04 华东师范大学 一种2’-脱氧-2’，2’-二氟-胞苷合成的方法
US8921340B2 (en) 2006-11-17 2014-12-30 Trustees Of Dartmouth College Methods for using synthetic triterpenoids in the treatment of bone or cartilage diseases or conditions
CA2670099A1 (en) 2006-11-17 2008-05-29 Trustees Of Dartmouth College Synthesis and biological activities of new tricyclic-bis-enones (tbes)
WO2008064132A2 (en) 2006-11-17 2008-05-29 Trustees Of Dartmouth College Synthetic triterpenoids and tricyclic-bis-enones for use in stimulating bone and cartilage growth
US20080262215A1 (en) * 2007-04-23 2008-10-23 Chemagis Ltd. Gemcitabine production process
CN100475832C (zh) * 2007-05-31 2009-04-08 南京卡文迪许生物工程技术有限公司 一种新颖的高立体选择性合成吉西他滨工艺及中间体
EP2048151A1 (de) * 2007-10-10 2009-04-15 Cilag AG Verfahren zur Herstellung von Nukleosiden durch direkte Glykosidation der Nukleosidbase
EP2050757A1 (de) * 2007-10-10 2009-04-22 Cilag AG Verfahren zur Herstellung von 2' -deoxy-5-Azacytidin (Decitabin)
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CN104250280A (zh) 2008-04-18 2014-12-31 里亚塔医药公司 抗氧化剂炎症调节剂:c-17同系化齐墩果酸衍生物
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JP5564490B2 (ja) 2008-04-18 2014-07-30 リアタ ファーマシューティカルズ インコーポレイテッド 抗炎症性ファルマコアを含む化合物および使用法
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JP6042527B2 (ja) 2012-04-04 2016-12-14 ハロザイム インコーポレイテッド 抗ヒアルロナン剤と腫瘍標的タキサンの組み合わせ治療
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CN110831605A (zh) 2017-04-26 2020-02-21 托马斯·I.·卡尔曼 多靶标的核苷衍生物
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US5371210A (en) * 1992-06-22 1994-12-06 Eli Lilly And Company Stereoselective fusion glycosylation process for preparing 2'-deoxy-2',2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides

Also Published As

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HU0201196D0 (de) 2002-06-29
JP3313191B2 (ja) 2002-08-12
KR940005658A (ko) 1994-03-22
HU9301822D0 (en) 1993-09-28
CA2098881A1 (en) 1993-12-23
UA41261C2 (uk) 2001-09-17
EP0577303B1 (de) 1997-10-01
GR3025689T3 (en) 1998-03-31
CY2067A (en) 1993-06-21
MX9303707A (es) 1994-06-30
NO180235C (no) 1997-03-12
DK0577303T3 (da) 1997-10-27
ATE158799T1 (de) 1997-10-15
MY115775A (en) 2003-09-30
NO180235B (no) 1996-12-02
NO932288A (no) 1993-12-23
FI932869A0 (fi) 1993-06-21
DE69314239D1 (de) 1997-11-06
HU223837B1 (hu) 2005-02-28
FI108643B (fi) 2002-02-28
DE69314239T2 (de) 1998-02-19
IL106071A (en) 2006-08-20
HUT64358A (en) 1993-12-28
PL299415A1 (en) 1994-03-07
PL172348B1 (pl) 1997-09-30
JPH06157570A (ja) 1994-06-03
EP0577303A1 (de) 1994-01-05
CA2098881C (en) 2005-06-07
NO932288D0 (no) 1993-06-21
KR100252452B1 (en) 2000-04-15
NO180235B3 (no) 2007-10-01
FI932869A (fi) 1993-12-23
NZ247939A (en) 1996-02-27
IL106071A0 (en) 1993-10-20
ES2107624T3 (es) 1997-12-01
BR9302434A (pt) 1994-02-16

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