SIOC English
有机化学
高级检索

有机化学 ›› 2009, Vol. 29 ›› Issue (11): 1768-1773. 上一篇    下一篇

研究论文

4-(4-β-D-吡喃阿洛糖苷-苯基)-2-芳基-5-氰基-6-甲氧基吡啶的合成及镇静活性研究

叶丁   付李   梁彬   尹述凡   李颖   

  1. (四川大学化学学院 成都 610041)
  • 收稿日期:2008-11-17 修回日期:2009-04-22 发布日期:2009-06-16
  • 通讯作者: 李颍 E-mail:chuandayouji217@163.com

Synthesis and Calm Aactivity of 4-(4-β-D-Allopyranosyloxyphenyl)-2- aryl-5-cyano-6-methoxypyridine Derivatives

Ye, Ding   Fu, Li    Liang, Bin    Yin, Shufan     Li, Ying   

  1. (Faculty of Chemistry, Sichuan University, Chengdu 610064)
  • Received:2008-11-17 Revised:2009-04-22 Published:2009-06-16

PDF

1266

以豆腐果苷为原料,与4-取代苯乙酮发生Schmidt-Claisen反应,得到一系列查儿酮结构的E-4-β-D-吡喃阿洛糖苷-苯乙烯基-4-取代苯乙酮衍生物3a-3h，其中3c、3e、3f为新化合物。 3a-3h在甲醇钠存在下，与1，3－丙二氰发生1,4-Michael加成，经关环、重排、氧化，得到4-(4-β-D-吡喃阿洛糖苷-苯基)-2-芳基-5-氰基-6-甲氧基吡啶系列豆腐果苷衍生物10a-10h,联氨催化还原10e而得到10i。共获得十二个未见文献报道的新化合物，其结构经1H NMR、IR和HRMS确证，并进行了药理活性筛选，结果表明，部分化合物具有比母体化合物更好的镇静催眠活性。同时，本文对Schmidt-Claisen反应存在的主要副反应进行了分析；对查儿酮与1，3－丙二氰在甲醇钠存在下反应生成吡啶衍生物反应机理进行了推导，提出了氧化脱氢形成吡啶的新机理。

关键词: 豆腐果苷, Schmidt-Claisen反应, 氧化脱氢, 反应机理, 吡啶

E-4-β-D-Allopyranoside–cinnamic-4-substituted phenyl ketone(3a-3h) which contains the structure of chalcone is synthesized by Schmidt-Claisen reaction with helicid and 4-sbstituted hypnone, by this way three new compounds : 3c、3e、3f are obtained. The chalcone is then reacted with malononitrile by Michael addition ,and followed by cyclization 、Dimroth rearrangement、oxidation , thus leads to the pyridine derivatives(10a-10h )of helicid. Catalytic reduction of 10e with hydrazine leads to 10i. A total of 12 unreported new compounds are obtained, the structure is confirmed by 1H NMR, IR and HRMS spectroscopy. The preliminary bioassay tests of 10a-10i show that some of the compounds have a better sedative and hypnotic activity. The major side reaction of Schimdt-Claisen condensation is analyzed. And the mechanism of oxydehydrogenation that leads to the formation of pyridine derivatives by the reaction of chalcone with malononitrile and sodium methoxide is firstly revealed.

Key words: helicid, Schmidt-Claisen reaction, oxydehydrogenation, reaction mechanism, pyridine