【摘要】：糖類及其綴合物具有許多生物活性,在生物體內(nèi)許多生理和病理過程中扮演著重要角色。其中,已有500多種被開發(fā)為糖類藥物,用于糖尿病、病毒感染、細菌感染及腫瘤的治療。然而,由于糖自身結(jié)構(gòu)復雜,含有多個手性中心,且通常含有多個極性基團如羥基、氨基等,很難通過從自然界中提取分離的方式獲得高純度、足夠量的生物活性寡糖及其綴合物,大大制約了對糖結(jié)構(gòu)和功能的研究進程。因此,發(fā)展糖的化學合成方法,制備出不同種類的糖類化合物,對糖化學、糖生物學及糖藥物學的發(fā)展都具有重要意義。本論文對一種新的糖苷化方法開展了研究。該方法選取2-(2-丙基硫基)芐基(PTB)和2-(2-丙基亞磺�；�)芐基(PSB)作為離去基。帶有PTB基團的隱蔽型糖基供體,通過簡單的氧化就可轉(zhuǎn)變?yōu)閹SB基團的活化型糖基供體。該活化型糖基供體在三氟甲磺酸酐(Tf2O)的作用下,經(jīng)過Interrupted Pummerer反應,就能與各種各樣的受體發(fā)生糖苷化反應。PTB官能團和PSB官能團實現(xiàn)了隱蔽型糖基供體向活化型糖基供體的高效轉(zhuǎn)化,為該方法在隱蔽/活化寡糖合成策略中的應用打下了基礎(chǔ)。該方法所用糖基供體不僅具有穩(wěn)定性好、糖苷化效率高等優(yōu)點,而且離去基PSB能夠回收(PSB-OH)或再生(PTB-OH)。在此基礎(chǔ)上,我們采用匯聚式[3+1]糖苷化反應完成了具有保肝活性的天然三糖-Leonoside F的全合成,糾正了文獻報道的Leonoside F的結(jié)構(gòu)。本研究為寡糖合成提供了一種新思路,為后續(xù)糖生物學及糖類藥物的研究奠定了基礎(chǔ)。
[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.
【學位授予單位】：華中科技大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R914
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本文編號：2495559