【作者】 乔珍；

【导师】 魏俊发；

【作者基本信息】 陕西师范大学 ， 有机化学， 2006， 硕士

【摘要】 反式-二苯乙烯（trans-Stilbene）类化合物,如白藜芦醇、Piceatannol、Combretastatin A-1等,具有抗老年痴呆、抗癌、抗菌、抗氧化、降低血脂等多种重要的生物学功能。由于新的药物作用靶点的不断更新,该类化合物的药物化学进展很快,形成了反式-二苯乙烯类化合物的新领域,是一类很有发展前景的化合物。由于反式-二苯乙烯类化合物独特的药效,已经引起了国内外学者的高度重视。 反式-二苯乙烯类化合物的天然来源十分有限,使得对其进行生物活性研究和应用开发受到一定限制,因此对反式-二苯乙烯的合成路线和方法进行研究显得十分重要,成为了人们关注的热点。研究证实,化学合成的该类化合物与天然提取的产物具有同样的生物活性。目前大部分合成反式-二苯乙烯类化合物的方法存在原料成本高,反应条件苛刻,操作繁杂等缺点,只能作为实验室规模的制备方法。因此,对反式-二苯乙烯的合成方法进行深入研究,寻找一种反应条件温和,原料成本低,操作相对简单的合成方法有着十分重要的意义。 基于以上原因,本文通过研究得到了合成反式-二苯乙烯类化合物的几种方法。 第一章中综述了反式-二苯乙烯类化合物的各种生物活性,以及反式-二苯乙烯类化合物的合成方法研究进展。 第二章以对硝基甲苯和取代苯甲醛为原料,研究了BTEAC/50%NaOH,KF/Al₂O₃,PEG-400/无水K₂CO₃三种不同催化体系下缩合脱水生成反式-二苯乙烯的反应,并探索了各种因素对反应收率的影响,优化了反应的工艺条件,三种催化体系产物收率均在80%以上。通过IR、¹H NMR、¹³C NMR、元素分析确定了反应产物的结构及其构型。结果表明,以该缩合反应构建反式-二苯乙烯桥具有路线简洁,操作简便,反式选择性高等特点。 第三章研究了（E）-3,5-二甲氧基-4′-硝基二苯乙烯在Fe-HCl,Zn-CaCl₂,NH₂NH₂·H₂O-KOH三种体系下,通过硝基还原反应,合成了（E）-3,5-二甲氧基-4′-氨基二苯乙烯。并探索了Zn-CaCl₂还原体系的各种因素对收率的影响,优化了反应的工艺条件,产物收率达到82%。反应中烯键不受影响。 第四章研究了McMurry偶联反应在反式-二苯乙烯化合物合成中的应用。利用McMurry偶联反应,以取代苯甲醛为原料,经Zn/TiCl₄还原合成了三种甲氧基取代的反式-二苯乙烯,其中一个为不对称反式取代二苯乙烯。实验表明,McMurry偶联反应可以方便、高产率的合成对称的反式-二苯乙烯化合物,且构型以反式为更多还原

【Abstract】 (E)-stilbenes, such as resveratrol, Piceatannol, Combretastatin A-1 et al, have taken extensive attention due to their outstanding biological activities and pharmacological properties including anti-inflammatory, antioxidation, platelet antiaggregation, heart protection and anticarcinogenic effects. However, the limited natural resource of （E）-stilbenes has restricted the research about their pharmacological activities and applications.It becomes much more important to search for the synthetic methods for preparation of （E）-stilbenes. Previous research has proved that the synthetic （E）-stilbenes have identical physiological action with that obtained from the natural source.In this thesis, three methods had been developed searching for a facile and highly stereoselective synthetic method for preparation of （E）-stilbenes.The first section is a summary on the biological activity and previous synthetic methods of （E）-stilbenes.In the second section four （E）-4-nitrostilbenes were synthesized in excellent yield by an efficient condensation dehydration of P-nitrotoluene with substituted benzaldehyde in the presence of three kinds of bases and catalysts. The optimal result was given after the various reaction conditions were investigated and the products are conformed by IR, ¹H NMR, ¹³C NMR, and element analysis. Therefore, the condensation reaction is a facile and highly stereoselective synthetic method to （E）-stilbenes.In the third section （E）-1-（4-nitrophenyl）-2-（3,5-dimethoxyphenyl）ethene was reduced by three kinds of systems（Fe-HCl, Zn-CaCl₂, NH₂NH₂H₂O-KOH）. （E）-1-（4-aminophenyl）-2-（3,5-dimethoxyphenyl）ethene was obtained in the high yield, and the persistence of configuration was investigated by IR and ¹H NMR.In the fourth section the application to synthesizing （E）-stilbenes of McMurry coupling reaction of aromatic aldehydes was studied. Three kinds of methoxy-substituted （E）-stilbenes were synthesized which has one asymmetric （E）-stilbene. It is found that symmetrical （E）-stilbenes are obtained with a higher selectivity and a good yield by McMurry coupling reaction. However, the products of crossed couplingreaction are complex and the yield is low.In the fifth section the application to synthesizing （E）-stilbenes of Grignard reaction was studied. Firstly, Grignard reagent was prepared by benzyl chloride or />methoxychlorobenzyl. 1,2-Diarylethanol was obtained by the reaction of Grignard reagent and substituted benzaldehyde. （E）-stilbene was obtained by dehydration. In this paper, Grignard reaction under ultrasonic radiation was studied. In comparison with conventional condention, it had no further use for harsh terms such as anhydrous solvent, inert atomosphere. And this paper examined effect of the pattern of substrate addition on Grignard reaction.更多还原