不同聚合度聚组氨酸的合成及其表征-西安培华学院.doc

题目 不同聚合度聚组氨酸的合成及其表征 作者姓名 高 霞 指导教师 周 四 元 二级学院 医 学 院 专 业 药 学 学 号 9B083134 2012 年5月15日 不同聚合度组氨酸的合成及其表征 摘 要 靶向是通过载体使药物选择性的浓集于病变部位的给药系统pH约为7.4，而肿瘤组织pH在6.4-6.8之间，肿瘤内的这些酸性环境可以作为靶向信号，为癌症的靶向治疗提供新的途径。 本实验拟采用组氨酸为起始原料，先与氯甲酸苄酯反应，生成化合物L-1 (2-((苄氧基羰基)氨基)-3-(1H-咪唑-5- 基)丙酸)，然后再与2,4-二硝基氟苯反应，生成L-2 (2 –((苄氧基羰基)氨基)-3- (1 –(2,4-二硝基苯基)-1H-咪唑-5-基)丙酸)，通过液质联用(LC-MS),超导核磁共振仪等确证化合物L-1,L-2的结构。L-2与氯化亚砜反应，生成L-3 (4-((1-(4-硝基苯基)-1H-咪唑-5-基)甲基)恶唑烷-2,5-二酮)，最后通过聚合反应得到不同聚合度的肿瘤靶向聚组氨酸材料。 关键词：靶向制剂；pH酸敏；聚组氨酸 Synthesis and characterization of different degree of polymerization of polyhistidine Abstract Targeting agent is also known as targeted drug delivery system, which can selectively carry drug to the lesion. The lesion is often referred to the target site. Some studies confirmed that the tumor tissue was acidic, pH at 6.4-6.8, while human bodys normal tissue pH is about 7.4. These acidic environment within the tumor can be used as target signal, to provide a new way for targeted therapy of cancer. In this study, we used histidine as the starting material. First it reacted with benzyl chloroformate to generate compound L-1(2 - ((benzyloxy-carbonyl) amino) -3 -(1H-imidazole -5--) propionic acid), and then reacted with 2,4 - dinitrofluorobenzene to gain the compound L-2 (2 - ((benzyloxy carbonyl) amino) -3 - (1 - (2,4 - dinitrophenyl)-1H-imidazole - 5--) propionic acid), The structure of compounds L-1, L-2 was confirmed by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance(NMR) and finally, there is a reaction between L-2 and thionyl chloride to produce L-3 (4 - ((1 - (4 - nitrophenyl)-1H-imidazole -5-- yl) methyl) evil oxazolidine-2,5 - dione). At the end, we expect to obtain a different degree of polymerization of tumor targeting poly-histidine materials through polymerization reaction. Key words: targeted drug delivery; pH sensitivity; polyhistidine.目 录 绪 论 1 1. 研究的目的和意义 2 1.1 研究的目的 2 1.2 研究的意义 3 2 实验