4-(苯乙烯基)苯酚的合成及抗肿瘤活性研究

Synthesis and anti-tumor activity evaluation of 4-styrylphenol

以(4-甲氧苯基)膦酸二乙酯为原料,在甲醇钠催化下,发生Wittig-Homor反应,得到4-甲氧基二苯乙烯(3),再经BBr3脱甲基得到了4-(苯乙烯基)苯酚(4),在乙醇中重结晶得到纯品,产品结构通过1H NMR表征。并优化了反应条件:在Wittig-Homor反应中,N,N-二甲基甲酰胺(DMF)为溶剂;甲醇钠为催化剂,n(4-甲氧苯基)膦酸二乙酯∶n甲醇钠=1∶5;室温反应时间12h;在脱甲基化反应中:BBr3为催化剂,n4-甲氧基二苯乙烯∶nBBr3=1∶3;反应温度为-20℃;优化条件下产物总收率为79.5%。初步的抗肿瘤活性测试结果表明,4-(苯乙烯基)苯酚对MCF-7、PC-3、HeLa和HepG2均有明显地抗增殖效果,尤其是对MCF-7展现出了强的抑制活性,其IC_(50)值为(19.9±2.5)μmol·L^(-1)。

Diethyl 4-methoxyphenylphosphonate was used as raw material to yield 4-Methoxystilbene(3)by Wittig-Homor reaction under the catalysis of sodium methoxide,and then(3)was demethylated to obtained 4-styrylphenol(4)by BBr3,which was crystallized in ethanol.The structure of the product was confirmed by 1H NMR.Moreover,the reaction conditions were optimized:in Wittig-Homor reaction,N,N-dimethylformamide(DMF)as solvent;sodium methoxide as catalyst;ndiethyl 4-methoxyphenylphosphonate∶nsodium methoxide=1∶5;reaction at room temperature for 12h;in demethylation reaction,BBr3 as catalyst;n4-methoxy stilbene∶nBBr3=1∶3;reaction temperature at-20℃;Under optimal conditions,the total of 4-styrylphenol was 79.5%.The preliminary biological results showed that 4-styrylphenol displayed obvious antiproliferative effect on MCF-7,PC-3,HeLa and HepG2 cell lines,especially to MCF-7,which showed strong inhibitory effect with the IC_(50) value was(19.9±2.5)μmol·L^(-1).