基于Interrupted Pummerer反应的糖苷化方法及其应用研究
发布时间：2019-06-09 12:31
【摘要】：糖类及其缀合物具有许多生物活性,在生物体内许多生理和病理过程中扮演着重要角色。其中,已有500多种被开发为糖类药物,用于糖尿病、病毒感染、细菌感染及肿瘤的治疗。然而,由于糖自身结构复杂,含有多个手性中心,且通常含有多个极性基团如羟基、氨基等,很难通过从自然界中提取分离的方式获得高纯度、足够量的生物活性寡糖及其缀合物,大大制约了对糖结构和功能的研究进程。因此,发展糖的化学合成方法,制备出不同种类的糖类化合物,对糖化学、糖生物学及糖药物学的发展都具有重要意义。本论文对一种新的糖苷化方法开展了研究。该方法选取2-(2-丙基硫基)苄基(PTB)和2-(2-丙基亚磺酰基)苄基(PSB)作为离去基。带有PTB基团的隐蔽型糖基供体,通过简单的氧化就可转变为带PSB基团的活化型糖基供体。该活化型糖基供体在三氟甲磺酸酐(Tf2O)的作用下,经过Interrupted Pummerer反应,就能与各种各样的受体发生糖苷化反应。PTB官能团和PSB官能团实现了隐蔽型糖基供体向活化型糖基供体的高效转化,为该方法在隐蔽/活化寡糖合成策略中的应用打下了基础。该方法所用糖基供体不仅具有稳定性好、糖苷化效率高等优点,而且离去基PSB能够回收(PSB-OH)或再生(PTB-OH)。在此基础上,我们采用汇聚式[3+1]糖苷化反应完成了具有保肝活性的天然三糖-Leonoside F的全合成,纠正了文献报道的Leonoside F的结构。本研究为寡糖合成提供了一种新思路,为后续糖生物学及糖类药物的研究奠定了基础。
[Abstract]:Carbohydrates and their conjugated compounds have many biological activities and play an important role in many physiological and pathological processes in organisms. Among them, more than 500 kinds of carbohydrates have been developed for diabetes, virus infection, bacterial infection and tumor treatment. However, because of the complex structure of sugar itself, containing multiple chiral centers, and usually containing multiple polar groups such as hydroxyl, amino and so on, it is difficult to obtain high purity by extraction and separation from nature. Enough bioactive oligosaccharide and its conjugated compounds greatly restrict the research process of sugar structure and function. Therefore, the development of chemical synthesis methods of sugar and the preparation of different kinds of carbohydrate compounds are of great significance to the development of sugar chemistry, sugar biology and sugar pharmacology. In this paper, a new glycoside method was studied. In this method, 2-(2-propylthio) benzyl( PTB) and 2-(2-propylsulfonyl) benzyl( PSB) were selected as departure groups. The hidden glycosyl donor with PTB group can be transformed into activated glycosyl donor with PSB group by simple oxidation. The activated glycosyl donor was reacted by Interrupted Pummerer under the action of trifluoromethylsulfonic anhydride (Tf2O). PTB functional group and PSB functional group can realize the efficient transformation from hidden glycosyl donor to activated glycosyl donor, which lays a foundation for the application of PTB functional group and PTB functional group in the synthesis strategy of hidden / activated oligosaccharide. The glycosyl donors used in this method not only have the advantages of good stability and high glycoside efficiency, but also can recover (PSB-OH) or regenerate (PTB-OH). On this basis, the total synthesis of natural triose-Leonoside F with hepatoprotective activity was completed by converging [31] glycoside reaction, and the structure of Leonoside F reported in the literature was corrected. This study provides a new idea for oligosaccharide synthesis and lays a foundation for the follow-up study of sugar biology and carbohydrates.
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R914
，
本文编号：2495559
[Abstract]:Carbohydrates and their conjugated compounds have many biological activities and play an important role in many physiological and pathological processes in organisms. Among them, more than 500 kinds of carbohydrates have been developed for diabetes, virus infection, bacterial infection and tumor treatment. However, because of the complex structure of sugar itself, containing multiple chiral centers, and usually containing multiple polar groups such as hydroxyl, amino and so on, it is difficult to obtain high purity by extraction and separation from nature. Enough bioactive oligosaccharide and its conjugated compounds greatly restrict the research process of sugar structure and function. Therefore, the development of chemical synthesis methods of sugar and the preparation of different kinds of carbohydrate compounds are of great significance to the development of sugar chemistry, sugar biology and sugar pharmacology. In this paper, a new glycoside method was studied. In this method, 2-(2-propylthio) benzyl( PTB) and 2-(2-propylsulfonyl) benzyl( PSB) were selected as departure groups. The hidden glycosyl donor with PTB group can be transformed into activated glycosyl donor with PSB group by simple oxidation. The activated glycosyl donor was reacted by Interrupted Pummerer under the action of trifluoromethylsulfonic anhydride (Tf2O). PTB functional group and PSB functional group can realize the efficient transformation from hidden glycosyl donor to activated glycosyl donor, which lays a foundation for the application of PTB functional group and PTB functional group in the synthesis strategy of hidden / activated oligosaccharide. The glycosyl donors used in this method not only have the advantages of good stability and high glycoside efficiency, but also can recover (PSB-OH) or regenerate (PTB-OH). On this basis, the total synthesis of natural triose-Leonoside F with hepatoprotective activity was completed by converging [31] glycoside reaction, and the structure of Leonoside F reported in the literature was corrected. This study provides a new idea for oligosaccharide synthesis and lays a foundation for the follow-up study of sugar biology and carbohydrates.
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R914
，
本文编号：2495559
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