酸催化α-细辛脑二聚反应及其产物抗癌活性研究

Acid-Catalyzed Dimerization of α-Asarone and Anticancer Evaluation of the Dimers

以E-1-(2,4,5-三甲氧基苯基)-2-丙烯(α-细辛脑)为原料,酸催化选择性合成脱碳木脂素类化合物a及二氢化茚类化合物b,其结构经核磁﹑质谱和元素分析表征确认.研究了催化剂种类、反应溶剂和温度等条件对两种化合物产率比的影响,45℃时,HCl为催化剂,乙醇为溶剂,化合物a/b的总收率为98%(a:41%,b:57%);30℃时,AlCl3为催化剂,乙醇为溶剂,化合物a的产率可达75%,没有b生成,对a的选择性为100%;45℃时,以BF3Et2O溶液为催化剂,CH2Cl2为溶剂,化合物a的产率为20%,化合物b的产率可达60%.采用MTT法,分别评价了化合物a/b对四种癌细胞(MCF-7,Bel-7402,A549及Hela)的抑制作用,结果表明:化合物a对MCF-7,Hela(IC50值分别为:120.2,117.3μmol L-1),化合物b则对MCF-7,A549(IC50值分别为:66.1,72.4μmol L-1)显示出比相同条件下5-Fu更好的抗癌抑制活性.同时,研究了a/b浓度﹑作用时间对癌细胞抑制率的影响.

The decarbonization of lignan a and dihydroindene b were synthesized through α-asarone by acid-catalyzed. Compounds a/b were identified by 1H NMR, 13C NMR, MS and elemental analysis. The effects of catalysts, solvents and temperature on yields of a/b have been evaluated. The total yield of a/b reached 98% （a： 41%, b： 57%） with HCl as catalyst and ethanol as solvent at 45 ℃. The yield of compound a was up to 75% with AlCl3 as catalyst and ethanol as solvent at 30 ℃, b was not formed in this condition, and the selectivity of a was 100%. When using BF3·Et2O as catalyst and methylene chloride as solvent at 45 ℃, the yield of compound a was 20% and b was formed in yield of 60%. The cytotoxic activities of two compounds against MCF-7, Bel-7402, A549 and Hela were evaluated in vitro by the MTT assay. The results indicated that compounds a/b exhibited better cytotoxic activities against four cancer cells than 5-Fu. Especially, the IC50 values of a to MCF-7 and Hela reached 120.2 and 117.3 μmol·L-1 as well as the IC50 of b to MCF-7 and A549 reached 66.1 and 72.4 μmol·L-1, respectively. At the same time, the concentration of a/b and time of operation to influence inhibitory activity were explored.