新型7-O-（芳基氨基甲酸酯）-布雷菲德菌素A的合成及其抗肿瘤活性.pdfVIP

学兔兔 2015年第23卷 合成化学 Vo1．23，2015 第1期，7～12 Chinese Journa1．of Synthetic Chemistry No．I，7—12 · 研究论文· 新型7-0．(芳基氨基甲酸酯)． 布雷菲德菌素A的合成及其抗肿瘤活性 吴植献，王亚军，陈 玮，薛 锋，万南微，郑裕国 (浙江工业大学生物工程研究所，浙江杭州 310014) 摘要：芳胺与三光气反应制得芳基异氰酸酯(2a一2n)；2a~2n分别对布雷菲德菌素A(3)的7-羟基进行结构 修饰，合成了14个新型布雷菲德菌素A氨基甲酸酯类衍生物——．7-0·(芳基氨基甲酸酯)一布雷菲德菌素A (4a一4n)，其结构经‘H NMR，”C NMR和ESI—HR-MS表征。初步的抗肿瘤活性测定结果表明，4i一4k均丧失 抑制食管癌细胞株TE．1活性。分子对接研究揭示，引入3后，4的分子空间位阻增大，导致不能与靶位结合， 致使抗肿瘤活性丧失。 关 键 词：布雷菲德菌素A；异氰酸酯；氨基甲酸酯；衍生化；合成；抗肿瘤活性 中图分类号：O621．3；R914．5 文献标识码：A DOI：10．15952／j．cnki．cjsc．1005—1511．2015．叭．0007 Synthesis and Anti-tumor Activities of Novel 7-O·(arylcarbamic ester)·Brefeldin A WU Zhi—xian， WANG Ya-jun， CHEN Wei， XUE Feng， WAN Nan—wei， ZHENG Yu—guo (Institute of Bioengineefing，Zhejiang Univemi~of Technology，Hangzhou 310014，China) Abstract：Arylisoeyanates(2a一2n)were prepared by the reaction of aromatic amines with triphos- gene．A series of novel carbamate derivatives including 7一O一(arylearbamie ester)一Brefeldin A(4a一 4n)．were synthesized by stucture modification of 2a一2n on 7-hydroxyl of Brefeldin A．The struc． tures were characterized by H NMR，”C NMR and ESI—HR—MS．Antipmliferative activities of 4g， 4i~41 were evaluated against esophageal cancer cell line TE一1．It was demonstrated that 4i一4k had no antitumor activities．Further molecular docking indicated that introduction of bulky groups to brefeldin A impeded their entry into the active—sites，leading to the loss of eytotoxity． Keywords：Brefeldin A；isoeyanate；earbamate；derivatization；synthes