Title:
METHOD FOR AUTOMATIC PREPARATION OF FONDAPARINUX SODIUM PENTOSACCHARIDE INTERMEDIATE
Document Type and Number:
WIPO Patent Application WO/2022/135319
Kind Code:
A1
Abstract:
The present invention relates to a method for the automatic preparation of a fondaparinux sodium pentasaccharide intermediate. The method is based on an automatic preparation device. According to the method, automatic preparation of three components (D+EF+GH) is realized by means of automatic sample injection, and automatic sampling and monitoring, so as to obtain the fully-protected fondaparinux sodium pentasaccharide intermediate (formula I), thereby realizing the automatic synthesis of the fondaparinux sodium pentasaccharide intermediate, saving on the investment of labor, improving the efficiency and productivity, and having a relatively high safety and reproducibility. The method can be directly monitored online, which is convenient for optimizing and monitoring the real-time status of the reaction. At the same time, the automatic temperature control can better meet the requirements of the reaction for heating and cooling. A pre-activation one-kettle mode is used, such that the number of times of separation are reduced and the operation is convenient. A common ester protecting group is selected, a relatively high stereoselectivity and yield are achieved, and a universal deprotection method can be used. The method has an important significance in reducing the production cost of fondaparinux sodium and achieving large-scale production thereof. The definition of each substituent in formula I is the same as the definition in the description.
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Inventors:
YE XINSHAN (CN)
YAO WENLONG (CN)
XIONG DECAI (CN)
YAO WENLONG (CN)
XIONG DECAI (CN)
Application Number:
PCT/CN2021/139518
Publication Date:
June 30, 2022
Filing Date:
December 20, 2021
Export Citation:
Assignee:
UNIV BEIJING (CN)
International Classes:
C07H15/203; C07H1/00
Foreign References:
| CN203414406U | 2014-01-29 | |||
| CN110779771A | 2020-02-11 | |||
| CN211436205U | 2020-09-08 | |||
| CN1558911A | 2004-12-29 | |||
| CN108101946A | 2018-06-01 | |||
| CN101104627A | 2008-01-16 | |||
| CN1966515A | 2007-05-23 | |||
| CN112552359A | 2021-03-26 |
Other References:
JIN HONGZHEN, CHEN QIANG, ZHANG YAN-YAN, HAO KAI-FENG, ZHANG GUO-QIANG, ZHAO WEI: "Preactivation-based, iterative one-pot synthesis of anticoagulant pentasaccharide fondaparinux sodium", ORGANIC CHEMISTRY FRONTIERS, vol. 6, no. 17, 20 August 2019 (2019-08-20), pages 3116 - 3120, XP055946458, DOI: 10.1039/C9QO00480G
DEY SUPRIYA, LO HONG-JAY, WONG CHI-HUEY: "Programmable One-Pot Synthesis of Heparin Pentasaccharide Fondaparinux", ORGANIC LETTERS, AMERICAN CHEMICAL SOCIETY, US, vol. 22, no. 12, 19 June 2020 (2020-06-19), US , pages 4638 - 4642, XP055946460, ISSN: 1523-7060, DOI: 10.1021/acs.orglett.0c01386
TULAY POLAT ET AL.: "Anomeric Reactivity-Based One-Pot Synthesis of Heparin-Like", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 129, 3 October 2007 (2007-10-03), XP055118018, DOI: 10.1021/ja073098r
CHEM. MED. CHEM, vol. 9, 2014, pages 1071 - 1080
J. ORG. CHEM., vol. 81, 2016, pages 162 - 184
ANGEW. CHEM. INT. ED., vol. 53, 2014, pages 9876 - 9879
ORG. CHEM. FRONT., vol. 6, 2019, pages 3116 - 3120
ORG. LETT., vol. 22, 2020, pages 4638 - 4642
SCIENCE, vol. 334, 2011, pages 498 - 501
DEY SUPRIYA, LO HONG-JAY, WONG CHI-HUEY: "Programmable One-Pot Synthesis of Heparin Pentasaccharide Fondaparinux", ORGANIC LETTERS, AMERICAN CHEMICAL SOCIETY, US, vol. 22, no. 12, 19 June 2020 (2020-06-19), US , pages 4638 - 4642, XP055946460, ISSN: 1523-7060, DOI: 10.1021/acs.orglett.0c01386
TULAY POLAT ET AL.: "Anomeric Reactivity-Based One-Pot Synthesis of Heparin-Like", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 129, 3 October 2007 (2007-10-03), XP055118018, DOI: 10.1021/ja073098r
CHEM. MED. CHEM, vol. 9, 2014, pages 1071 - 1080
J. ORG. CHEM., vol. 81, 2016, pages 162 - 184
ANGEW. CHEM. INT. ED., vol. 53, 2014, pages 9876 - 9879
ORG. CHEM. FRONT., vol. 6, 2019, pages 3116 - 3120
ORG. LETT., vol. 22, 2020, pages 4638 - 4642
SCIENCE, vol. 334, 2011, pages 498 - 501
Attorney, Agent or Firm:
BEIJING GAOWO LAW FIRM (CN)
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