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

Info

Publication number
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
Authority
CN
China
Prior art keywords
compound
formula
base
hydroxyl protection
protection base
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.)
Active
Application number
CN201480059909.2A
Other languages
English (en)
Chinese (zh)
Other versions
CN105683198A (zh
Inventor
F.G.方
D-S.金
H-W.蔡
C.E.查斯
J.李
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.)
Sanitary Material R&d Management Co ltd
Original Assignee
Sanitary Material R&d Management Co ltd
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
Application filed by Sanitary Material R&d Management Co ltd filed Critical Sanitary Material R&d Management Co ltd
Priority to CN202210377346.8A priority Critical patent/CN114716453A/zh
Priority to CN201910122043.XA priority patent/CN109942560B/zh
Publication of CN105683198A publication Critical patent/CN105683198A/zh
Application granted granted Critical
Publication of CN105683198B publication Critical patent/CN105683198B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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

Landscapes

  • 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)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyrane Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Saccharide Compounds (AREA)
  • Steroid Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (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)

Priority Applications (2)

Application Number Priority Date Filing Date Title
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
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

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
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

Related Child Applications (2)

Application Number Title Priority Date Filing Date
CN202210377346.8A Division 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
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

Publications (2)

Publication Number Publication Date
CN105683198A CN105683198A (zh) 2016-06-15
CN105683198B true CN105683198B (zh) 2019-03-12

Family

ID=53005318

Family Applications (3)

Application Number Title Priority Date Filing Date
CN201480059909.2A Active CN105683198B (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
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
CN202210377346.8A Pending 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

Family Applications After (2)

Application Number Title Priority Date Filing Date
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
CN202210377346.8A Pending 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

Country Status (12)

Country Link
US (5) US9783549B2 (enExample)
EP (2) EP3066102B1 (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
KR101434673B1 (ko) 2004-06-03 2014-08-26 에자이 알앤드디 매니지먼트 가부시키가이샤 할리콘드린 ｂ 유사체의 제조를 위한 중간체
EP2578576B9 (en) 2007-10-03 2016-09-14 Eisai R&D Management Co., Ltd. Intermediates for the synthesis of halichondrin B analogs
RU2517167C2 (ru) 2008-04-04 2014-05-27 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Аналоги галихондрина в
US8203010B2 (en) 2010-01-26 2012-06-19 Eisai R&D Management Co., Ltd. Compounds useful in the synthesis of halichondrin B analogs
CA2929084C (en) 2013-11-04 2022-01-11 Eisai R&D Management Co., Ltd. Macrocyclization reactions and intermediates and other fragments useful in the synthesis of analogs of halichondrin b
BR112016012237B1 (pt) 2013-12-06 2023-02-07 Eisai R&D Management Co., Ltd Métodos úteis na síntese de análogos de halicondrina b
WO2016003975A1 (en) 2014-06-30 2016-01-07 President And Fellows Of Harvard College Synthesis of halichondrin analogs and uses 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
MX392296B (es) 2015-05-07 2025-03-24 Eisai R&D Man Co Ltd Reacciones de macrociclizacion e intermediarios y otros fragmentos utiles en la sintesis de macrolidos de halicondrina.
WO2017064627A2 (en) * 2015-10-14 2017-04-20 Dr. Reddy's Laboratories Limited Process for preparation of eribulin and intermediates thereof
MX377663B (es) 2016-02-12 2025-03-11 Eisai R&D Man Co Ltd Intermediarios en la sintesis de eribulina y metodos de sintesis relacionados.
MY199595A (en) 2016-03-02 2023-11-08 Eisai R&D Man Co Ltd Eribulin-based antibody-drug conjugates and methods of use
US11136335B2 (en) * 2016-06-30 2021-10-05 Eisai R&D Management Co., Ltd. Prins reaction and intermediates useful in the synthesis of halichondrin macrolides and analogs thereof
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
SI3606928T1 (sl) * 2017-04-05 2023-02-28 President And Fellows Of Harvard College Makrociklična spojina in njene uporabe
WO2018217894A1 (en) * 2017-05-24 2018-11-29 Eisai R&D Management Co., Ltd. Fluorine-labelled halichondrin derivatives and related methods of synthesis
HUE061306T2 (hu) 2017-07-06 2023-06-28 Harvard College Halikondrinok szintézise
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
WO2019093776A1 (ko) * 2017-11-09 2019-05-16 연성정밀화학(주) 에리불린 메실산염의 제조 중간체 및 그의 제조방법
CN111566113B (zh) 2017-11-15 2024-01-09 哈佛大学的校长及成员们 大环化合物及其用途
EP3713565A1 (en) 2017-11-20 2020-09-30 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
MX2020006945A (es) 2018-01-03 2020-11-09 Eisai R&D Man Co Ltd Reaccion de prins y compuestos utiles en la sintesis de macrolidos de halicondrina y analogos de los mismos.
US11396515B2 (en) * 2018-03-02 2022-07-26 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
CN119585437A (zh) * 2022-07-29 2025-03-07 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
US8097648B2 (en) 1998-06-17 2012-01-17 Eisai R&D Management Co., Ltd. Methods and compositions for use in treating cancer
CA2632433C (en) 1998-06-17 2012-02-07 Eisai R & D Management Co., Ltd. Methods for preparing macrocyclic analogs and intermediates for preparing same
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
KR101434673B1 (ko) 2004-06-03 2014-08-26 에자이 알앤드디 매니지먼트 가부시키가이샤 할리콘드린 ｂ 유사체의 제조를 위한 중간체
JP2008522623A (ja) 2004-12-09 2008-07-03 エーザイ株式会社 ハリコンドリンｂアナログを使用した癌治療でのチューブリンアイソタイプのスクリーニング
EP1940758B1 (en) 2005-09-26 2012-11-28 Symrise AG Intramolecular prins reaction
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
CN101910180A (zh) 2007-11-16 2010-12-08 卫材R&D管理有限公司 用于软海绵素b类似物合成的新颖中间体和用于该中间体的新颖脱磺酰化反应
RU2517167C2 (ru) 2008-04-04 2014-05-27 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Аналоги галихондрина в
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
CA2857385A1 (en) * 2011-11-30 2013-06-06 Alphora Research Inc. Process for preparation of (3r)-2,4-di-leaving group-3-methylbut-1-ene
WO2015000070A1 (en) 2013-07-03 2015-01-08 Alphora Research Inc. Synthetic process for preparation of macrocyclic c1-keto analogs of halichondrin b and intermediates useful therein including intermediates containing -so2-(p-tolyl) groups
CA2929084C (en) 2013-11-04 2022-01-11 Eisai R&D Management Co., Ltd. Macrocyclization reactions and intermediates and other fragments useful in the synthesis of analogs of halichondrin b
BR112016012237B1 (pt) * 2013-12-06 2023-02-07 Eisai R&D Management Co., Ltd Métodos úteis na síntese de análogos de halicondrina b
US10208058B2 (en) 2014-09-09 2019-02-19 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
MX392296B (es) * 2015-05-07 2025-03-24 Eisai R&D Man Co Ltd Reacciones de macrociclizacion e intermediarios y otros fragmentos utiles en la sintesis de macrolidos de halicondrina.
MX377663B (es) 2016-02-12 2025-03-11 Eisai R&D Man Co Ltd Intermediarios en la sintesis de eribulina y metodos de sintesis relacionados.
US11136335B2 (en) 2016-06-30 2021-10-05 Eisai R&D Management Co., Ltd. Prins reaction and intermediates useful in the synthesis of halichondrin macrolides and analogs thereof
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
MX2020006945A (es) 2018-01-03 2020-11-09 Eisai R&D Man Co Ltd Reaccion de prins y compuestos utiles en la sintesis de macrolidos de halicondrina y analogos de los mismos.

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. *

Also Published As

Publication number Publication date
US20200223864A1 (en) 2020-07-16
US20180002342A1 (en) 2018-01-04
IL244694B (en) 2019-07-31
IL288468B2 (en) 2023-02-01
IL288468A (en) 2022-01-01
BR112016009452B1 (pt) 2022-06-07
US20210188867A1 (en) 2021-06-24
CN109942560A (zh) 2019-06-28
US10221189B2 (en) 2019-03-05
US10611773B2 (en) 2020-04-07
US10934307B2 (en) 2021-03-02
EP3689881A1 (en) 2020-08-05
CN114716453A (zh) 2022-07-08
IL267936A (en) 2019-09-26
JP2020059728A (ja) 2020-04-16
EP3066102A4 (en) 2017-04-26
IL244694A0 (en) 2016-04-21
IL275240B (en) 2022-01-01
EP3066102A1 (en) 2016-09-14
IL275240A (en) 2020-07-30
RU2016121648A (ru) 2017-12-08
JP6909840B2 (ja) 2021-07-28
US20160264594A1 (en) 2016-09-15
US20190144463A1 (en) 2019-05-16
BR112016009452A8 (pt) 2020-03-24
US9783549B2 (en) 2017-10-10
HUE049387T2 (hu) 2020-09-28
EP3689881B1 (en) 2022-01-12
CN109942560B (zh) 2022-06-17
JP6625533B2 (ja) 2019-12-25
ES2787603T3 (es) 2020-10-16
RU2016121648A3 (enExample) 2018-08-06
JP2020023521A (ja) 2020-02-13
CN105683198A (zh) 2016-06-15
JP2016536316A (ja) 2016-11-24
IL288468B (en) 2022-10-01
CA2929084C (en) 2022-01-11
CA2929084A1 (en) 2015-05-07
SG11201603490TA (en) 2016-05-30
WO2015066729A1 (en) 2015-05-07
EP3066102B1 (en) 2020-02-26
IL267936B (en) 2020-06-30
US11643418B2 (en) 2023-05-09
RU2710545C2 (ru) 2019-12-27
JP6889232B2 (ja) 2021-06-18

Similar Documents

Publication Publication Date Title
CN109942560B (zh) 软海绵素b的类似物合成中有用的大环化反应和中间体
CN107849057B (zh) 用于合成软海绵素大环内酯的大环化反应及中间体和其他片段
JP7440563B2 (ja) ハリコンドリンマクロライドおよびその類縁体の合成に有用なプリンス反応および中間体
CN111868044B (zh) 可用于合成软海绵素大环内酯及其类似物的普林斯反应和化合物

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant