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

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。

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

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.