【作者】 王浩；

【导师】 万谦；

【作者基本信息】 华中科技大学 ， 药物化学， 2018， 博士

【摘要】 2-脱氧糖是很多具有生物活性的临床药物和天然产物的重要组成部分,也是它们发挥生物活性所必需的结构单元。然而,天然产物中2-脱氧糖类化合物的含量很低,并且存在形式较为复杂,很难通过天然提取的方式获得足量、高纯度的2-脱氧糖类化合物,大大限制了其在医药研究中的应用。因此,通过化学合成途径合成2-脱氧糖片段就变得非常必要。但是由于其C-2位缺少立体选择性导向基团,使得产物的立体选择性控制困难;并且2-脱氧糖糖苷键稳定性较差、易水解,这些因素使得2-脱氧糖苷的立体选择性合成非常具有挑战性。相较于直接合成法,间接合成法是高立体选择性合成2-脱氧-α-糖苷最有效的方法。但是现有间接合成法中,碘原子的引入反应效率较低、产物分离困难,碘原子脱除也大都使用有毒试剂或者反应效率较低,这些因素极大的限制了2-脱氧-α-糖苷类化合物,特别是具有医药价值2-脱氧-α-糖苷类化合物的合成。本论文基于可见光催化反应温和、高效的特点,发展了一种铱催化剂介导的可见光催化脱碘方法。通过细致的机理研究,发现反应中对甲基苯硫酚是反应的供氢体和供电子体。应用此方法,我们成功实现了多种糖类碘代物碘原子的高效脱除,为2-脱氧-α-糖苷的合成奠定了基础。本论文进一步利用间接合成法,通过对2-碘-2-脱氧-α-糖基乙酸酯供体合成方法的改进,以及对糖基化反应条件的优化,高效、单一选择性的制备出多种不同类型的2-碘-2-脱氧-α-糖苷。应用本论文发展的可见光催化脱碘方法,高效的完成了2-碘-2-脱氧-α-糖苷中碘原子的脱除,实现了多种类型2-脱氧-α-糖苷化合物的合成。该方法为具有生物活性的复杂2-脱氧糖类天然产物和药物分子的合成提供了一种新的选择,也为后续糖生物学、糖药物学的研究奠定了物质基础。更多还原

【Abstract】 2-Deoxy sugars are not only a component of natural products and clinical medicines,but also the necessary building blocks for their biological activities.However,the content of 2-deoxyglycosides in natural products is very low and the forms are complicated.It is difficult to obtain a sufficient amount of 2-deoxyglycosides with high-purity by natural extraction methods,which greatly limit its application in medicine.Hence,it becomes necessary to synthesize 2-deoxyglycosides by chemical approaches.Nevertheless,due to the lack of stereoselective directing group in the C-2 position and the unstability of glycosidic bond,the stereoselective synthesis of 2-deoxyglycosides are very challenging.Compared to direct strategy,indirect strategy is the most efficient method for highly stereoselective synthesizing 2-deoxy-α-glycosides.However,in indirect methods,the introduction reactions of iodine atom are inefficient and the separation of products is difficult.In addition,the removal reactions of iodine atom always use toxic reagents or the efficiency is low.These factors greatly limit the synthesis of 2-deoxy-α-glycosides,especially bioactive 2-deoxy-α-glycosides.Based on photocatalysis mild and efficient feature,we developed a novel visible-light mediated deiodination reaction.It was found that p-toluenethiol was the hydrogen donor and electron donor for the reaction.Finally,this method was successfully applied in deiodination of various iodides,which laid the foundation for the synthesis of 2-deoxy-α-glycosides.In this thesis,we used indirect synthetic method to accomplish the synthesis of diversified 2-deoxy-α-glycosides,which provided a new alternative for the synthesis of biologically active complex natural products and drug molecules.In addition,this method laid the foundation for future study on glycobiology and carbohydrate-based drugs.更多还原