Title:
INTERMEDIATE OF ERIBULIN, SYNTHESIS METHOD THEREFOR AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2020/216034
Kind Code:
A1
Abstract:
Provided are an intermediate which can be used for synthesizing halichondrin B, eribulin or an analogue thereof, in particular a C27-C35 structure fragment thereof, a preparation method therefor and use thereof. The starting raw materials of the synthetic route are cheap and easily available, and the optical purity thereof can be ensured, thereby ensuring the optical purity of the C27-C35 structure fragment in halichondrin, eribulin or an analogue thereof. The step and method for constructing the chiral center of C27-C35 structure fragment has high diastereoselectivity and yield, especially the preparation method for the compounds represented by formula (X), formula (XI), formula (XVI) and formula (XV). Some reaction by-products can be removed only by means of recrystallization, which facilitates purification and greatly reduces costs.
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Inventors:
XU WEIPING (CN)
Application Number:
PCT/CN2020/082933
Publication Date:
October 29, 2020
Filing Date:
April 02, 2020
Export Citation:
Assignee:
BEIJING TIENYI LUFU PHARMATECH CO LTD (CN)
International Classes:
C07C43/23; C07C41/26; C07D301/24; C07D303/04; C07D317/22; C07D407/06; C07F7/08; C07F7/18
Foreign References:
| CN105524064A | 2016-04-27 | |||
| CN103237780A | 2013-08-07 | |||
| CN106946906A | 2017-07-14 | |||
| DE10258226A1 | 2004-07-08 |
Other References:
SRINIVAS, THEEGALA ET AL.: "Total Synthesis of Catenioblin B", TETRAHEDRON LETTERS, vol. 55,, no. 43,, 16 September 2014 (2014-09-16), XP029049447, ISSN: 0040-4039, DOI: 20200514170643X
GOTO, TOMOMI ET AL.: "Total Synthesis of Four Stereoisomers of (4Z, 7Z, 10Z, 12E, 16Z, 18E)-14, 20-Dihydroxy-4, 7, 10, 12, 16, 18-Docosahexaenoic Acid and Their Anti-inflammatory Activities", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 80, no. 15, 14 July 2015 (2015-07-14), XP055746302, ISSN: 0022-3263, DOI: 15144309X
ORITA, AKIHIRO ET AL.: "Integration of Solventless Reaction in a Multi-Step Process:Application to an Efficient Synthesis of PA-824", ADVANCED SYNTHESIS & CATALYSIS, vol. 349, no. 13, 6 September 2007 (2007-09-06), XP055746267, ISSN: 1615-4169, DOI: 20200515145257X
MURGA, JUAN ET AL.: "Stereoselective Synthesis of Microcarpalide", ORGANIC LETTERS, vol. 4, no. 20, 30 August 2002 (2002-08-30), XP055746265, ISSN: 1523-7060, DOI: 20200515150142X
ZHENG, WANJUN ET AL.: "Macrocyclic Ketone Analogues of Halichondrin B", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 14, no. 22, 21 September 2004 (2004-09-21), XP004598592, ISSN: 0960-894X, DOI: 20200514170815X
ZHENG, WANJUN ET AL.: "Macrocyclic Ketone Analogues of Halichondrin B", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 14, no. 22, 21 September 2004 (2004-09-21), XP004598592, ISSN: 0960-894X, DOI: 20200515141311X
See also references of EP 3925948A4
GOTO, TOMOMI ET AL.: "Total Synthesis of Four Stereoisomers of (4Z, 7Z, 10Z, 12E, 16Z, 18E)-14, 20-Dihydroxy-4, 7, 10, 12, 16, 18-Docosahexaenoic Acid and Their Anti-inflammatory Activities", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 80, no. 15, 14 July 2015 (2015-07-14), XP055746302, ISSN: 0022-3263, DOI: 15144309X
ORITA, AKIHIRO ET AL.: "Integration of Solventless Reaction in a Multi-Step Process:Application to an Efficient Synthesis of PA-824", ADVANCED SYNTHESIS & CATALYSIS, vol. 349, no. 13, 6 September 2007 (2007-09-06), XP055746267, ISSN: 1615-4169, DOI: 20200515145257X
MURGA, JUAN ET AL.: "Stereoselective Synthesis of Microcarpalide", ORGANIC LETTERS, vol. 4, no. 20, 30 August 2002 (2002-08-30), XP055746265, ISSN: 1523-7060, DOI: 20200515150142X
ZHENG, WANJUN ET AL.: "Macrocyclic Ketone Analogues of Halichondrin B", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 14, no. 22, 21 September 2004 (2004-09-21), XP004598592, ISSN: 0960-894X, DOI: 20200514170815X
ZHENG, WANJUN ET AL.: "Macrocyclic Ketone Analogues of Halichondrin B", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 14, no. 22, 21 September 2004 (2004-09-21), XP004598592, ISSN: 0960-894X, DOI: 20200515141311X
See also references of EP 3925948A4
Attorney, Agent or Firm:
BEIJING ORIGINTELLIGENCE IP LAW FIRM (CN)
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