缩硫脲类荧光探针分子的合成  

Synthesis of the fluorescent probe molecule of thiosemicarbazones

作　　者：黄亚飞[1,2] 钟武[2] 李松[2] 

机构地区：[1]中南大学湘雅医学院药学院,长沙410013 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《军事医学》2013年第7期539-542,共4页Military Medical Sciences

基　　金：国家科技支撑计划资助项目(2011BAI18B01)

摘　　要：目的合成带有Halo-tag专属性配基小分子的缩硫脲(缩氨基硫脲)化合物,作为研究抗肿瘤金属螯合剂作用机制的探针分子。方法以相应的酮为原料与肼基甲硫酸甲硫酯缩合,缩合物用2-(2-氨基乙氧基)乙醇取代其中甲硫基,得到重要中间体3酮缩4-[2-(2-羟基乙氧基)乙基]氨基硫脲,最后再与6-氯-1-溴己烷发生亲核取代反应生成目标化合物酮缩4-(2-[2-(6-氯己氧基)乙氧基]乙基)-3-氨基硫脲。目标化合物结构经1H-NMR、13C-NMR和LC-MS确认。结果与结论建立了抗肿瘤金属螯合剂与Halo-tag的专属性配基分子结合的制备路线,合成了3个连接Halo-tag专属性配基和高活性抗肿瘤金属螯合剂的探针分子,为研究该类抗肿瘤金属螯合剂的作用机制提供了工具分子。Objective To synthesize the Halo-tag specific ligand of thiosemicarbazones that can be used as probe mole- cules to study the mechanism of action of anti-tumor metal chelators. Methods The target compounds, synthesized from ketone and methyl hydrazinecarbodithioate,reacted with 2-（2-aminoethoxy）ethanol to obtain intermediate 3 ketone- 4 [ 2 - （2 -hydroxyethoxy） ethyl ]-3- thiosemicarbazide before reacting with intermediate 3 and 1-bromo-6-chlorohexane via nucleo- philic substitution to obtain the target compounds ketone-4- （2 - （2 - （6- chlorohexyloxy）-ethoxy） ethyl）-3 thiosemicarbaz- ide. The structure of the compounds was confirmed by 1H-NMR, 13 C-NMR and LC-MS. Results and Conclusion A method of connecting Halo-tag specific ligand with anti-tumor metal chelators was established. Three fluorescent probe molecules of thiosemicarbazones were synthesized that can be used to study the mechanism of action of anti-tumor metal chelators.

关 键 词：HALOTAG 连接子 金属螯合剂 抗肿瘤 

分 类 号：R914[医药卫生—药物化学]