CN105683198B - 软海绵素b的类似物合成中有用的大环化反应和中间体 - Google Patents

软海绵素b的类似物合成中有用的大环化反应和中间体 Download PDF

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CN105683198B
CN105683198B CN201480059909.2A CN201480059909A CN105683198B CN 105683198 B CN105683198 B CN 105683198B CN 201480059909 A CN201480059909 A CN 201480059909A CN 105683198 B CN105683198 B CN 105683198B
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formula
base
hydroxyl protection
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CN105683198A (zh
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F.G.方
D-S.金
H-W.蔡
C.E.查斯
J.李
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Sanitary Material R&d Management Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen 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
    • C07D307/28—Heterocyclic compounds containing five-membered rings having one oxygen 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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
    • 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
    • C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
    • C07D493/14—Ortho-condensed systems
    • 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
    • C07D493/22—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero 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
    • 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
    • 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrane Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Saccharide Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Steroid Compounds (AREA)
CN201480059909.2A 2013-11-04 2014-11-04 软海绵素b的类似物合成中有用的大环化反应和中间体 Active CN105683198B (zh)

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CN201910122043.XA CN109942560B (zh) 2013-11-04 2014-11-04 软海绵素b的类似物合成中有用的大环化反应和中间体
CN202210377346.8A CN114716453A (zh) 2013-11-04 2014-11-04 软海绵素b的类似物合成中有用的大环化反应和中间体

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US201361899697P 2013-11-04 2013-11-04
US61/899697 2013-11-04
PCT/US2014/063960 WO2015066729A1 (en) 2013-11-04 2014-11-04 Macrocyclization reactions and intermediates useful in the synthesis of analogs of halichondrin b

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CN201910122043.XA Division CN109942560B (zh) 2013-11-04 2014-11-04 软海绵素b的类似物合成中有用的大环化反应和中间体

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CN201910122043.XA Active CN109942560B (zh) 2013-11-04 2014-11-04 软海绵素b的类似物合成中有用的大环化反应和中间体

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CN201910122043.XA Active CN109942560B (zh) 2013-11-04 2014-11-04 软海绵素b的类似物合成中有用的大环化反应和中间体

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US (5) US9783549B2 (enExample)
EP (2) EP3689881B1 (enExample)
JP (3) JP6625533B2 (enExample)
CN (3) CN105683198B (enExample)
BR (1) BR112016009452B1 (enExample)
CA (1) CA2929084C (enExample)
ES (1) ES2787603T3 (enExample)
HU (1) HUE049387T2 (enExample)
IL (4) IL244694B (enExample)
RU (1) RU2710545C2 (enExample)
SG (1) SG11201603490TA (enExample)
WO (1) WO2015066729A1 (enExample)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL2522663T3 (pl) 2004-06-03 2015-08-31 Eisai R&D Man Co Ltd Produkty pośrednie do otrzymywania halichondryny B
EP2578576B9 (en) 2007-10-03 2016-09-14 Eisai R&D Management Co., Ltd. Intermediates for the synthesis of halichondrin B analogs
US8598373B2 (en) 2008-04-04 2013-12-03 Eisai R&D Management Co., Ltd. Halichondrin B analogs
SG182612A1 (en) 2010-01-26 2012-08-30 Eisai R&D Man Co Ltd Furo [3, 2 -b] pyrane derivatives useful in the synthesis of halichondrin b analogs
HUE049387T2 (hu) 2013-11-04 2020-09-28 Eisai R&D Man Co Ltd A halichondrin B analógjainak szintézisében hasznos makrociklizációs reakciók és köztitermékek
SG11201604545XA (en) 2013-12-06 2016-07-28 Eisai R&D Man Co Ltd Methods useful in the synthesis of halichondrin b analogs
JP2017520586A (ja) 2014-06-30 2017-07-27 プレジデント アンド フェローズ オブ ハーバード カレッジ ハリコンドリン類似体の合成およびその使用
WO2016176560A1 (en) 2015-04-30 2016-11-03 President And Fellows Of Harvard College Chromium-mediated coupling and application to the synthesis of halichondrins
KR102743950B1 (ko) 2015-05-07 2024-12-18 에자이 알앤드디 매니지먼트 가부시키가이샤 할리콘드린 마크롤라이드의 합성에 유용한 마크로고리화 반응 및 중간체 및 기타 단편
WO2017064627A2 (en) * 2015-10-14 2017-04-20 Dr. Reddy's Laboratories Limited Process for preparation of eribulin and intermediates thereof
JP6786610B2 (ja) * 2016-02-12 2020-11-18 エーザイ・アール・アンド・ディー・マネジメント株式会社 エリブリンの合成における中間体および関連する合成方法
KR102456433B1 (ko) 2016-03-02 2022-10-19 에자이 알앤드디 매니지먼트 가부시키가이샤 에리불린-기반 항체-약물 콘주게이트 및 사용 방법
MX390072B (es) * 2016-06-30 2025-03-20 Eisai R&D Man Co Ltd Reaccion de prins e intermediarios utiles en la sintesis de macrolidos de halicondrina y analogos de los mismos.
JP6978758B2 (ja) 2016-11-11 2021-12-08 プレジデント アンド フェローズ オブ ハーバード カレッジ パラジウム媒介ケトール化
US9938288B1 (en) 2017-04-05 2018-04-10 President And Fellows Of Harvard College Macrocyclic compound and uses thereof
HRP20221385T1 (hr) * 2017-04-05 2023-01-06 President And Fellows Of Harvard College Makrociklički spoj i njegova uporaba
WO2018217894A1 (en) * 2017-05-24 2018-11-29 Eisai R&D Management Co., Ltd. Fluorine-labelled halichondrin derivatives and related methods of synthesis
US11548898B2 (en) 2017-07-06 2023-01-10 President And Fellows Of Harvard College Synthesis of halichondrins
US11498892B2 (en) 2017-07-06 2022-11-15 President And Fellows Of Harvard College Fe/Cu-mediated ketone synthesis
CN109694379B (zh) * 2017-10-24 2020-09-11 江苏恒瑞医药股份有限公司 用于制备艾日布林的中间体及其制备方法
KR102177992B1 (ko) * 2017-11-09 2020-11-12 연성정밀화학(주) 에리불린 메실산염의 제조 중간체 및 그의 제조방법
EP3710454B1 (en) 2017-11-15 2024-01-03 President And Fellows Of Harvard College Macrocyclic compounds and uses thereof
US11419856B2 (en) 2017-11-20 2022-08-23 Basilea Pharmaceutica International AG Pharmaceutical combinations for use in the treatment of neoplastic diseases
CN109970822B (zh) * 2017-12-27 2023-03-28 上海科胜药物研发有限公司 一种合成埃格列净中间体的制备方法
KR102799793B1 (ko) 2018-01-03 2025-04-25 에자이 알앤드디 매니지먼트 가부시키가이샤 할리콘드린 마크롤리드 및 그의 유사체의 합성에 유용한 프린스 반응 및 화합물
EP3608323B1 (en) * 2018-03-02 2021-11-03 Beijing Tienyi Lufu Pharmatech Co. Ltd. Pyran fused ring compound, preparation method therefor and use thereof
WO2019211877A1 (en) * 2018-05-03 2019-11-07 Cipla Limited Process for the preparation of macrocyclic ketone analogs of halichondrin b
CN112437775A (zh) * 2018-07-20 2021-03-02 雷迪博士实验室有限公司 用于制备艾日布林及其中间体的纯化方法
US11447499B2 (en) * 2019-06-14 2022-09-20 Rk Pharma Inc. Process for the preparation of eribulin mesylate intermediate
CN110684036B (zh) * 2019-11-22 2022-04-12 江苏慧聚药业股份有限公司 一条制备甲磺酸艾日布林的方法
WO2023144733A1 (en) * 2022-01-26 2023-08-03 Simon Fraser University Compounds and processes for the preparation of eribulin
WO2024021261A1 (zh) * 2022-07-29 2024-02-01 上海皓元医药股份有限公司 一种艾日布林中间体的制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060045846A1 (en) * 2004-08-30 2006-03-02 Horstmann Thomas E Reagents and methods for labeling terminal olefins
CN1993342A (zh) * 2004-06-03 2007-07-04 卫材株式会社 用于制备软海绵素b的中间体
WO2008010776A1 (en) * 2006-07-21 2008-01-24 Agency For Science, Technology And Research Aigialomycin d and derivatives thereof and their use in treating cancer or malaria or a microbial infection
US20110184190A1 (en) * 2010-01-26 2011-07-28 Eisai R&D Management Co., Ltd. Compounds useful in the synthesis of halichondrin b analogs
WO2013142999A1 (en) * 2012-03-30 2013-10-03 Alphora Research Inc. Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein

Family Cites Families (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4107206A (en) 1974-04-08 1978-08-15 Akzona Incorporated Benzo-bicyclononene- derivatives
SU652180A1 (ru) 1975-12-16 1979-03-15 Краснодарский политехнический институт 1(Фурил-2,)-2-(2-,, формилфурил-5,, ) этилен или его метильное производное как промежуточный продукт дл синтеза фуран-2,5-дикарбоновой кислоты и способ его получени
US5338865A (en) 1992-03-12 1994-08-16 President And Fellows Of Harvard College Synthesis of halichondrin B and norhalichondrin B
US5436238A (en) 1992-03-12 1995-07-25 President And Fellows Of Harvard College Halichondrins and related compounds
GB9206244D0 (en) 1992-03-23 1992-05-06 Pharma Mar Sa Cytotoxic compound from a marine sponge
TW255880B (enExample) 1992-09-09 1995-09-01 Hoechst Ag
WO1998009942A1 (en) 1996-09-06 1998-03-12 Eli Lilly And Company Catalytic selective sulfonylation process
US6870058B2 (en) 1996-12-03 2005-03-22 The Trustees Of The University Of Pennsylvania Compounds which mimic the chemical and biological properties of discodermolide
IL139960A0 (en) 1998-06-17 2002-02-10 Eisai Co Ltd Macrocylic analogs and methods of their use and preparation
US8097648B2 (en) 1998-06-17 2012-01-17 Eisai R&D Management Co., Ltd. Methods and compositions for use in treating cancer
US6653341B1 (en) 1998-06-17 2003-11-25 Eisai Co., Ltd. Methods and compositions for use in treating cancer
DE10106647A1 (de) 2001-02-12 2002-08-22 Univ Hannover Ratjadon-Derivate zum Hemmen des Zellwachstums
PL2522663T3 (pl) 2004-06-03 2015-08-31 Eisai R&D Man Co Ltd Produkty pośrednie do otrzymywania halichondryny B
WO2006076100A2 (en) 2004-12-09 2006-07-20 Eisai Co. Ltd. Tubulin isotype screening in cancer therapy using halichondrin b analogs
JP2009510005A (ja) 2005-09-26 2009-03-12 シムライズ・ゲゼルシヤフト・ミツト・ベシユレンクテル・ハフツング・ウント・コンパニー・コマンジツト・ゲゼルシヤフト 分子内プリンス反応および該反応に適する触媒
JPWO2009014105A1 (ja) 2007-07-20 2010-10-07 株式会社山田養蜂場本社 新規カルボン酸およびそれを有効成分とする抗うつ用組成物
EP2578576B9 (en) 2007-10-03 2016-09-14 Eisai R&D Management Co., Ltd. Intermediates for the synthesis of halichondrin B analogs
CA2705383A1 (en) 2007-11-16 2009-05-22 Eisai R&D Management Co., Ltd. Novel intermediate for halichondrin b analog synthesis and novel desulfonylation reaction used for the intermediate
US8598373B2 (en) 2008-04-04 2013-12-03 Eisai R&D Management Co., Ltd. Halichondrin B analogs
JP5371091B2 (ja) 2009-01-23 2013-12-18 三菱レイヨン株式会社 モノスルホン酸エステルの製造方法
WO2012147900A1 (en) 2011-04-28 2012-11-01 Eisai R&D Management Co., Ltd. Microreactor process for halichondrin b analog synthesis
AU2012344697A1 (en) * 2011-11-30 2014-07-10 Alphora Research Inc. Process for preparation of (3R)-2,4-di-leaving group-3-methylbut-1-ene
JP6511613B2 (ja) 2013-07-03 2019-05-15 サンド・アクチエンゲゼルシヤフト ハリコンドリンＢの大環状Ｃ１−ケト類似体の製造のための合成方法及び該方法に有用な中間体、例えば−ＳＯ２−（ｐ−トリル）基を含有する中間体
HUE049387T2 (hu) 2013-11-04 2020-09-28 Eisai R&D Man Co Ltd A halichondrin B analógjainak szintézisében hasznos makrociklizációs reakciók és köztitermékek
SG11201604545XA (en) 2013-12-06 2016-07-28 Eisai R&D Man Co Ltd Methods useful in the synthesis of halichondrin b analogs
WO2016038624A1 (en) 2014-09-09 2016-03-17 Cipla Limited "process for the preparation of macrocyclic ketone analogs of halichondrin b or pharmaceutically acceptable salts and intermediates thereof"
WO2016176560A1 (en) * 2015-04-30 2016-11-03 President And Fellows Of Harvard College Chromium-mediated coupling and application to the synthesis of halichondrins
KR102743950B1 (ko) 2015-05-07 2024-12-18 에자이 알앤드디 매니지먼트 가부시키가이샤 할리콘드린 마크롤라이드의 합성에 유용한 마크로고리화 반응 및 중간체 및 기타 단편
JP6786610B2 (ja) 2016-02-12 2020-11-18 エーザイ・アール・アンド・ディー・マネジメント株式会社 エリブリンの合成における中間体および関連する合成方法
MX390072B (es) 2016-06-30 2025-03-20 Eisai R&D Man Co Ltd Reaccion de prins e intermediarios utiles en la sintesis de macrolidos de halicondrina y analogos de los mismos.
US20180009825A1 (en) * 2016-07-06 2018-01-11 Apicore Us Llc Methods of making eribulin mesylate
WO2018217894A1 (en) 2017-05-24 2018-11-29 Eisai R&D Management Co., Ltd. Fluorine-labelled halichondrin derivatives and related methods of synthesis
KR102799793B1 (ko) 2018-01-03 2025-04-25 에자이 알앤드디 매니지먼트 가부시키가이샤 할리콘드린 마크롤리드 및 그의 유사체의 합성에 유용한 프린스 반응 및 화합물

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1993342A (zh) * 2004-06-03 2007-07-04 卫材株式会社 用于制备软海绵素b的中间体
US20060045846A1 (en) * 2004-08-30 2006-03-02 Horstmann Thomas E Reagents and methods for labeling terminal olefins
WO2008010776A1 (en) * 2006-07-21 2008-01-24 Agency For Science, Technology And Research Aigialomycin d and derivatives thereof and their use in treating cancer or malaria or a microbial infection
US20110184190A1 (en) * 2010-01-26 2011-07-28 Eisai R&D Management Co., Ltd. Compounds useful in the synthesis of halichondrin b analogs
WO2013142999A1 (en) * 2012-03-30 2013-10-03 Alphora Research Inc. Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
David J. Del Valle 等.Total Synthesis of (+)-Trienomycins A and F via C−C Bond-Forming Hydrogenation and Transfer Hydrogenation.《Journal of the American Chemical Society》.2013,第135卷第10986-10989页，尤其Scheme 4，10988页左栏第1段. *

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