以Heck型反应构建碳苷二糖以及C-KRN7000的全合成研究

发布时间：2018-03-07 15:34

本文选题：Heck反应　切入点：碳苷　出处：《复旦大学》2014年硕士论文　论文类型：学位论文

【摘要】：糖类化合物尽管具有良好的生理活性,但是它们自身的一‘些缺陷限制了其成药的可能性,其中最典型的便是氧糖苷键的不稳定性,因此,碳苷的研究便显得尤为熏要。其中,碳苷二糖不仅本身具有生理活性,而且可以作为复杂分子合成的砌块。但是,现有的碳苷二糖的合成方法相当有限,因此,发展简洁高效的碳苷二糖的合成方法是非常有意义的。本文中,我们发展了一种通过碘代外糖烯(exo-glycal)和内糖烯(endo-glycal)进行Heck类型偶联反应生成碳苷一糖的有效方法。经过条件优化发现,使用Pd(OAc)2作为催化剂、dppp作为配体、K2C03作为碱时,反应以高产率给出了碳苷二糖产物,并且具有完全的立体选择性。进一步,我们尝试了将碳苷二糖作为手性合成子应用到复杂天然产物的合成中。KRN7000碳苷(C-KRN7000)是一种引起广泛兴趣的免疫促进剂,结构中包括一个半乳糖部分和一个神经酰胺部分,两者通过·碳苷键连接；神经酰胺部分含有三个手性中心。其合成具有一定的挑战性。本课题计划使用Suzuki-Miyaura反应首先构建碳苷二糖,然后打开其中一个糖环,以手性池策略构建侧链三个手性中心。该方法与已报道方法相比,路线简洁,并可以减少不对称操作。目前的工作主要集中在运用Suzuki-Miyaura反应首先构建碳苷二糖一步。
[Abstract]:Although carbohydrates have good physiological activity, their own defects limit the possibility of their proprietary medicines, the most typical of which is the instability of oxyglycoside bonds, so the study of carbohydrates is particularly important. Glycoside disaccharide not only has physiological activity, but also can be used as a building block for complex molecular synthesis. However, the existing methods of synthesis of carbon glycoside disaccharide are quite limited, so, It is of great significance to develop a simple and efficient method for the synthesis of carbon glycoside disaccharides. We have developed an effective method for the Heck type coupling reaction of iodide exo-glycaland endo-glycal. by optimizing the conditions, it was found that when Pd(OAc)2 was used as the catalyst, the ligand K2C03 was used as the base. The reaction gives the product of carbon glycoside disaccharide in high yield, and has complete stereoselectivity. We have tried to use carbon glycoside disaccharide as a chiral synthesizer in the synthesis of complex natural products. KRN7000 C KRN7000) is a widely interesting immune promoter with a galactose component and a ceramide part in the structure. The ceramide part contains three chiral centers. Its synthesis is challenging. We plan to use the Suzuki-Miyaura reaction to construct carbon glycoside disaccharide first, and then to open one of the sugar rings. Three chiral centers of side chain were constructed by chiral pool strategy. Compared with the reported method, this method is simple and can reduce asymmetric operation. The current work is mainly focused on the construction of one-step carbon glycoside disaccharide by using Suzuki-Miyaura reaction.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5

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