http://jcps.bjmu.edu.cn

中国药学(英文版) ›› 2018, Vol. 27 ›› Issue (7): 460-468.DOI: 10.5246/jcps.2018.07.047

• 【研究论文】 • 上一篇    下一篇

无配体钯催化的Suzuki羰基化反应研究及其在α7 nAChR 正向变构调节剂改造中的应用

孟盈1, 邹文星1, 黄宗泽1, 王新童2, 焦文宣1, 谢文军1, 卞希玲2, 王克威2,3*, 孙崎1*   

  1. 1. 北京大学医学部 药学院 天然药物及仿生药物国家重点实验室; 化学生物学系, 北京 100191
    2. 北京大学医学部 药学院 分子与细胞药理学系, 北京 100191
    3. 青岛大学 药学院 药理学系, 山东 青岛 266021
  • 收稿日期:2018-04-28 修回日期:2018-05-13 出版日期:2018-07-25 发布日期:2018-05-24
  • 通讯作者: Tel.: +86-532-82991070; +86-010-82801504, E-mail: wangkw@qdu.edu.cn; sunqi@bjmu.edu.cn
  • 基金资助:
    The National Natural Science Foundation of China (Grant No. 21572011 and 21272009).

Development of palladium-catalyzed Suzuki carbonylation reaction without external ligand and its application in modification of novel series of α7 nAChR PAMs

Ying Meng1, Wenxing Zou1, Zongze Huang1, Xintong Wang2, Wenxuan Jiao1, Wenjun Xie1, Xiling Bian2, KeWei Wang2,3*, Qi Sun1*   

  1. 1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
    2. Department of Molecular and cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
    3. Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266021, China
  • Received:2018-04-28 Revised:2018-05-13 Online:2018-07-25 Published:2018-05-24
  • Contact: Tel.: +86-532-82991070; +86-010-82801504, E-mail: wangkw@qdu.edu.cn; sunqi@bjmu.edu.cn
  • Supported by:
    The National Natural Science Foundation of China (Grant No. 21572011 and 21272009).

摘要:

本文在无外在配体的条件下, CHCl3为羰基化试剂, 实现了钯催化Suzuki羰基化反应。通过芳碘化物、氯仿和芳基硼酸的偶联反应探索了不同的取代二苯甲酮类化合物, 产率由中等到良好。基于前期α7乙酰胆碱受体正向变构调节剂的初步构效关系, 我们将这个反应方法应用于系列化合物的结构改造中。

关键词: 羰基化反应, 钯催化, 二苯甲酮类, CO替代试剂

Abstract:

Palladium-catalyzed Suzuki carbonylation with CHCl3 as carbonylative reagent was realized without external ligands. Different substituted benzophenones were explored via the coupling reaction of aryl iodides, arylboronic acids and CHCl3 as a CO surrogate in moderate to good yields. This method was also successfully applied to the structure modification of α7 nicotinic acetylcholine receptor positive allosteric modulators (α7 nAChR PAMs) based on the preliminary structure-activity relationship. 

Key words: Carbonylation reaction, Palladium-catalysis, Benzophenones, CO surrogate

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