3-(3,5-二甲氧基苯乙烯基)苯酚的合成及抗肿瘤活性研究

Synthesis and Antitumor Activity of 3-(3,5-Dimethoxystyryl)phenol

以3-甲氧基苄基磷酸二乙酯(Ⅰ)为原料,首先经三溴化硼脱甲基得到3-羟基苄基磷酸二乙酯(Ⅱ),随后在甲醇钠的催化下与3,5-二甲氧基苯甲醛(Ⅲ)发生Wittig-Horner反应得到3-(3,5-二甲氧基苯乙烯基)苯酚(Ⅳ),采用核磁共振氢谱表征其结构,并优化了反应条件。确定最佳的脱甲基化反应条件为:BBr_(3)为脱甲基试剂,其用量为n(Ⅰ)∶n(BBr_(3))=1∶3;Wittig-Horner反应条件为:甲醇钠用量为n(Ⅱ)∶n(甲醇钠)=1∶1.5、120℃反应5 h;在优化反应条件下,化合物Ⅳ总收率为67.2%。生物活性测试表明,化合物Ⅳ对肿瘤细胞MCF-7、PC-3、HeLa和HepG2均有明显的抑制活性,尤其是对HeLa细胞展现出了较强的抑制活性,其IC_(50)值为(11.80±1.27)μmol·L^(-1)。

Firstly,we obtained 3-hydroxybenzyldiethylphosphate(Ⅱ)from 3-methoxybenzyldiethylphosphate(Ⅰ)through demethylation by boron tribromide,then we obtained 3-(3,5-dimethoxystyryl)phenol(Ⅳ)by the Wittig-Horner reaction of 3,5-dimethoxybenzaldehyde(Ⅲ)with compoundⅡcatalyzed by sodium methoxide.Moreover,we characterized their structures by ^(1)HNMR,and optimized the reaction conditions.The optimal demethylation reaction conditions are determined as follows:BBr_(3) is adopted as the demethylation reagent,and its dosage is n(Ⅰ)∶n(BBr_(3))of 1∶3;the Wittig-Horner reaction conditions are as follows:the dosage of sodium methoxide is n(Ⅱ)∶n(sodium methoxide)of 1∶1.5,and the reaction temperature is 120℃for 5 h.Under above reaction conditions,the total yield of compoundⅣcan reach 67.2%.The biological activity test shows that compoundⅣexhibits significant antitumor activity against MCF-7,PC-3,HeLa,and HepG2 cells,especially exhibits strong inhibitory activity against HeLa cells with IC_(50) value of(11.80±1.27)μmol·L^(-1).