菜单
  
    摘要:姜黄素是对称分子结构的多酚类化合物,由具有β-二酮的庚二烯和两个邻甲基化的酚相连接组成的。天然的姜黄素主要来源于姜黄、郁金等姜黄属植物中,这些植物常作为活血化瘀中药使用。近年来,姜黄素因为有许多的药理作用引起了人们的广泛关注,其中它抗肿瘤活性的研究是最多的,也因此成为了研究热点。同时,虽然姜黄素耐热性好且毒性低,但水溶性差,结构不稳定,易降解,使其生物利用率极低。然而,剂型改造、同源类似物改造和前药修饰解决了姜黄素应用中存在的缺陷问题。其中,对姜黄素母体结构进行前药设计是有效的一种方法。28271
    本实验通过改造酚羟基来增加姜黄素衍生物的稳定性,通过小分子的修饰改善姜黄素应用上的缺点。由于对磷有机化合物的研究是最发展的,而且含磷有机化合物具有很强的生物活性,因此,我们考虑用磷酯类改造姜黄素的酚羟基,从而改善姜黄素的水溶性、稳定性,提高姜黄素的生物利用率。文献表明,姜黄素前药设计使其抗肿瘤活性及其它药理活性在医学上得到广泛的研究及应用。
    毕业论文关键词:姜黄素;磷酸酯类前药设计;抗肿瘤
    The design and synthesis of phosphoric curcumin derivatives
    Abstract: Curcumin is the symmetry of the molecular structure of polyphenol compounds which connected by a beta diketone of diene and two adjacent methylation of phenol. Natural curcumin mainly comes from curcuma plants such as turmeric, radix curcumae. These plants are often used as a traditional Chinese medicine for activating blood circulation. In recent years, because curcumin has a lot of pharmacological activity, it attracted widespread attention and its antitumor activity has become a hot research topic. At the same time, the curcumin has good heat resistance and low toxicity, but it is insoluble in water, and the structure is not stable, and it is easy to degradate, these makes its biological utilization rate extremely low. However, reconstruction of dosage forms, homologous analogues and prodrug 
    modification solve the problems that existing in the application of curcumin defects. Among these methods, prodrug modification is one of the effective methods.
        In this experiment, we modified the phenolic hydroxyl group in order to increase the stability of curcumin derivatives, through small molecule modification to improve the defects in application of curcumin. Due to the study of organic phosphorus compounds is the development, and organic phosphorus compounds have a strong biological activity, therefore, we consider using phosphorus esters transformation of curcumin phenolic hydroxyl, thereby improving the water-soluble, the stability and the bioavailability of curcumin. Literature suggests that curcumin prodrug design makes its antitumor activity and other pharmacological activities has been widely research and application in medicine.
    Key words:Curcumin;the design of phosphate ester prodrug;antieoplastic
    目 录
    1 前言
      1.1 抗肿瘤药物的研究1
      1.2 姜黄素药理作用概况 1
      1.3 姜黄素的剂型改造及前药修饰 2
      1.4含磷有机化合物的生物活性  3
      1.5 磷酸酯前药应用 4
    2 文献综述和方案论证
      2.1二烷基亚磷酸酯的合成方式5
        2.1.1 以PCl3、醇(ROH)和水为原料的制取法5
        2.1.2 二烷基亚磷酸酯的酯交换法 6
        2.1.3以PCl3和醇(ROH)为原料的合成方法6
      2.2 方案论证及实验路线的确定 7
    3 实验部分
      3.1 实验仪器及试剂8
      3.2二烷基亚磷酸酯的合成8
    3.3两种含磷反应物的合成8
    3.3.1 Ⅰ的合成  8
    3.3.2 Ⅱ的合成 10
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