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
收稿日期: 2015-02-03
修回日期: 2015-03-09
网络出版日期: 2015-03-17
基金资助
国家“十二五”科技支撑计划(No. 2012BAD31B02)和湖南省自然科学基金(No. 14JJ2048)资助项目.
Synthesis and Biological Activity of BenzodihydrofuranNeolignans and Their Mannich Base Derivatives
Received date: 2015-02-03
Revised date: 2015-03-09
Online published: 2015-03-17
Supported by
Project supported by the National“Twelfth Five-Year”Plan for Science & Technology Support (No. 2012BAD31B02) and the Hunan Provincial Natural Science Foundation of China (No. 14JJ2048).
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licarin A (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-(3'-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1HNMR、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 (IC50 0.438 μmol/L)和化合物9 (IC50 8.358 μmol/L)具有最强的Hela细胞增殖抑制活性.
关键词： 苯并二氢呋喃新木脂素; licarin A; Mannich 碱衍生物; 合成; 生物活性
史玲 , 王彩芳 , 徐雨 , 汪秋安 . 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[J]. 有机化学, 2015 , 35(7) : 1537 -1543 . DOI: 10.6023/cjoc201502003
The natural benzodihydrofuran neolignans licarin A (1) was synthesized from isoeugenol through biomimetic oxidative 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-1,4-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.
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