【作者】 赵军峰；

【导师】 廖新成；

【作者基本信息】 郑州大学 ， 有机化学， 2007， 硕士

【摘要】 羟基(9，10-)蒽醌具有抗癌、抗肿瘤、抑制生物体中由于过氧化反应导致的多种疾病的作用；而许多药物分子在磷酰化后具备了更多独特的生物活性和药理特性。因此磷酰化羟基蒽醌的合成和从分子水平上研究其与生物大分子之间的相互作用，对药物开发与研制具有重要意义。本文利用经改造并较简化的Atheron-Todd合成法，分别以亚磷酸二乙酯和亚磷酸二异丙酯为磷酰化试剂，成功对1，2-二羟基蒽醌、2，6-二羟基蒽醌、1，8-二羟基蒽醌和1，4-二羟基蒽醌进行了磷酰化改造；合成了九个未见文献报道的羟基蒽醌类的磷酰酯类衍生物。其合成路线如下图：所得化合物结构均经核磁共振、红外和电喷雾质谱确证。对四个二羟基蒽醌中不同取代位置的羟基的反应活性进行对比，发现β-羟基的反应活性高于α-羟基的反应活性，量子化学计算其电荷分布也得到了同样的结论。本文通过荧光分析法研究了磷酰化羟基蒽醌与牛血清白蛋白(BSA：Bovine serum albumin)之间的弱相互作用，并用荧光猝灭原理计算了它们之间的结合常数，作用力类型。结果证明，磷酰化羟基蒽醌与牛血清白蛋白发生了弱相互作用，它们之间的结合常数均为10~5，有1个结合位点，作用力类型属于氢键或范德华力。更多还原

【Abstract】 9,10- anthraquinones multi hydroxy derivatives have anticancer function and can inhibit multifarious diseases in organism caused by oxidation reactions. Many medical molecules have many unique activities and characteristics after being phosphorylated. It is very important to synthesis new phosphoryl dihydroxy-anthraquinones and research interaction detween them and biological macromoleculer for exploration of new drug.In this thesis,by Atheron-Todd reaction ,using diethyl phosphate and diisopropyl phosphate as phosphorylate reagents,we successfully synthesized a series of new dihydroxy-anthraquinones phosphate derivatives. The synthesis route was shown as following scheme. Their structures were confirmed by NMR, IR and ESI-MS. It was found that the reaction activities ofβ-hydroxyl multi- anthraquinones is much higher than those ofα-hydroxyl, which have been further confirmed by charge distributing analysis.The interactions of phosphoryly dihydroxy anthraquinone and BSA was confirmed by Fluorescence Analysis, which coubld be further used as a a powerful tool for screening numerous small molecule-protein complexes, due to its rapidity of data acquisition and the relative simplicity of interpretation. The results show that the binding constants between them are all about 10~5, and the number of bind site is 1 respectively, and the type of applied force between them is Van-der Waals Force and hydrogen bond.更多还原