苯并二氢呋喃新木脂素Mannich碱衍生物的合成及生物活性研究

Synthesis and Biological Activity of Benzodihydrofuran Neolignans and Their Mannich Base Derivatives

以异丁香酚为原料，经氧化银催化的自由基仿生氧化偶联反应，一步合成了天然苯并二氢呋喃新木脂素licarinA（1），然后经2，3-二氯-5，6-二氰基对苯醌（DDQ）氧化脱氢反应得到另一苯并二氢呋喃新木脂素化合物2-（31-甲氧基-4＇-羟基）苯基-3-甲基-5-甲酰乙烯基-7-甲氧基-2，3-苯并二氢呋喃（2）．以苯并二氢呋喃新木脂素1和2为底物，以甲醇为溶剂，分别与甲醛、二级胺在酸性介质中发生微波协助的Mannich反应，合成了11个新的苯并二氢呋喃新木脂素Mannich碱衍生物3～13．所合成的化合物通过’HNMR、13CNMR和MS等进行了结构确证，并采用CCK-8法测试了所合成化合物对人宫颈癌Hela细胞株的体外抑制活性．结果表明大部分化合物对Hela细胞增殖具有良好的抑制作用．其中化合物2（IC500．438μmol／L）和化合物90c508．358μmol／L）具有最强的Hela细胞增殖抑制活性．

The natural benzodihydrofuran neolignans licarin A （1） was synthesized from isoeugenol through biomimetic oxi- dative coupling. Then licarin A （1） was transformed into another benzodihydrofuran compound 2-（3＇-methoxy-4＇-hydroxy）- phenyl-3-methyl-5-formylvinyl-7-methoxy-2,3-benzodihydrofuran （2） through 2,3-dichloro-5,6-dicyano-l,4-benzoquinone （DDQ） oxidative reaction. Based on Mannich reaction of 1 or 2 with viarious secondary amines and formaldehyde in acidic alcohol system under microwave-assistanced, eleven new benzodihydrofuran neolignan Mannich base derivatives 3-13 were synthesized. All the synthetic compounds were tested for antiproliferation activity against human cervical carcinoma Hela cells by the standard CCK-8 method. The results showed that most of the target compounds exhibited moderate to potent antiproliferation activity against Heala cells. Among them, compound 2 （IC50 0.438 μmol/L） and compound 9 （IC50 8.358 μmol/L） displayed the strongest antiproliferation activity against Hela cells.