聚乙二醇及其衍生物的合成研究

发布时间：2018-03-22 06:00

本文选题：聚乙二醇　切入点：十二甘醇　出处：《华东师范大学》2017年硕士论文　论文类型：学位论文

【摘要】：聚乙二醇是一类由乙二醇聚合而成的化合物。聚乙二醇具有无毒、无免疫原性、无抗原性、生物相容性良好、价廉易得等优点,能够与各种药物通过共价键或者非共价键的方式偶联,PEG修饰的药物能大大增加药物水溶性并增加在体内的稳定性,并延长药物半衰期。目前聚乙二醇合成方法报道较少,本文旨在探究新型的单分散聚乙二醇及聚乙二醇衍生物的合成方法,并设计以聚乙二醇为亲水端的新型材料。论文第一部分工作研究了单分散聚乙二醇的合成方法,对传统的单分散聚乙二醇合成工艺进行了改进,且该改进路线具有一定的普适性。此外还对单分散聚乙二醇氨基化衍生物的合成做了探究,发展了一条路线短、操作简单合成工艺,降低了单分散聚乙二醇氨基化衍生物的生产成本。最后我们还对mPEG-NH2的合成方法进行了优化,设计出了一种基于Mitsunobu反应的新型mPEG-NH2合成方法,该方法相较于传统方法操作大大简便,且产品质量得到了显著提升。论文的第二部分中,我们设计出两个聚乙二醇修饰的自裂解材料,均以mPEG-NH2为亲水端,以多个碳酸酯与氨基甲酸酯为骨架,并分别以硼酸酯与硝基为触发点。首先我们研究了化合物亲脂端的具体合成方法,在完成化合物的合成之后探究了两个化合物在水中自组装的情况,此外我们希望探究其在过氧化氢环境下与还原环境下的稳定性。
[Abstract]:Polyethylene glycol (PEG) is a class of compounds polymerized from ethylene glycol. Polyethylene glycol has the advantages of non-toxic, non-immunogenicity, no antigenicity, good biocompatibility, cheap and easy to obtain, etc. Drugs that can be coupled with various drugs by covalent or non-covalent bonds can greatly increase their water solubility, increase their stability in vivo and prolong their half-life. The purpose of this paper is to study the synthesis method of monodisperse polyethylene glycol and its derivatives, and to design a new kind of material with polyethylene glycol as hydrophilic end. The first part of this paper studies the synthesis method of monodisperse polyethylene glycol. The traditional synthesis process of monodisperse polyethylene glycol is improved, and the improved route has certain universality. In addition, the synthesis of monodisperse polyethylene glycol amino derivatives has been explored, and a short route has been developed. The production cost of monodisperse poly (ethylene glycol) amino derivatives was reduced. Finally, the synthesis method of mPEG-NH2 was optimized, and a new mPEG-NH2 synthesis method based on Mitsunobu reaction was designed. Compared with the traditional method, the method is much easier to operate, and the quality of the product has been greatly improved. In the second part of the thesis, we designed two polyethylene glycol modified self-pyrolysis materials with mPEG-NH2 as hydrophilic terminal. Several carbonates and carbamate were used as the skeleton, and borate and nitro were used as trigger points respectively. Firstly, we studied the specific synthesis method of lipophilic end of compounds. After the synthesis of the compounds, the self-assembly of the two compounds in water was investigated. In addition, we hope to investigate the stability of the compounds in hydrogen peroxide and reduction environment.
【学位授予单位】：华东师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O632.3

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