石松生物碱Lycopalhine A关键中间体烯酮衍生物合成及手性炔烃分离方法研究

发布时间：2018-05-01 16:20

本文选题：石松生物碱 + Lycopalhine　；参考：《山西师范大学》2017年硕士论文

【摘要】：Palhinine类生物碱是近年来我国不同科研小组从不同产地的石松中分离出的具有笼状立体结构的一类石松生物碱。因为其结构复杂性,国内外已有多个课题组参与其合成竞争。Lycopalhine A作为Palhinine类石松生物碱中结构最为复杂的一个,含有9个手性碳原子,其中有8个连续相邻;另外,分子中的8个单环结构形成了复杂的笼状结构。Lycopalhine A在天然石松中含量极低,分离提纯的样品不足满足其生物活性筛选。因此简洁高效的全合成方法就显得尤为重要。本论文的主要工作集中在Lycopalhine A关键中间体烯酮衍生物合成及其结构鉴定方面。分别在非手性和手性条件下完成了关键中间体烯酮衍生物外消旋体和左、右旋体的合成,还对其中涉及的Pauson-Khand反应进行了系统的方法学研究。新颖手性炔烃化合物也是合成Lycopalhine A的关键中间体。对其进行手性分离及光学纯度测定具有非常重要的意义。由于结构中的炔基、烯基及烷基不是很好的固定相,且炔基和烯基并不是一个很好的紫外生色团,所以无法直接通过手性柱HPLC进行分离、分析。而利用制备HPLC衍生化反应需要繁琐的检测过程。本论文发展了一种使用手性HPLC法通过分离、分析手性炔烃钴配合物方法测定炔烃化合物的光学纯度新方法。设计利用手性炔烃化合物炔基原位与Co2(CO)8配位生成稳定的手性Co2(CO)6-aIkyne配合物,通过对该配合物进行液相分离、分析,间接测定了原手性炔烃化合物的光学纯度。该方法适用范围,广泛适用于没有经典生色团的炔烃类化合物。
[Abstract]:Palhinine alkaloids are a kind of Chinese pine alkaloids with cage solid structure which were isolated from different producing areas by different research groups in China in recent years. Because of its complex structure, many domestic and foreign research groups have participated in the synthesis competition. Lycopalhine A is the most complicated one of the alkaloids of Palhinine pine, which contains 9 chiral carbon atoms, 8 of which are adjacent to each other. The complex cage structure, Lycopalhine A, was formed in 8 monocyclic structures of the molecule, and the content of Lycopalhine A in natural pine was very low. The samples isolated and purified could not satisfy the screening of biological activity. Therefore, a simple and efficient total synthesis method is particularly important. The main work of this thesis is focused on the synthesis and structure identification of Lycopalhine A key intermediate ketene derivatives. The synthesis of racemes, left and right racemes of key intermediate ketene derivatives was carried out under the condition of non-chiral and chiral respectively, and the Pauson-Khand reactions involved in them were systematically studied. Novel chiral alkynes are also the key intermediates in the synthesis of Lycopalhine A. Chiral separation and optical purity determination are of great significance. Because the alkynyl, alkyl and alkyl in the structure are not very good stationary phase, and the alkyl and alkyl are not a good UV chromophore, they can not be separated and analyzed directly by chiral column HPLC. However, the preparation of HPLC derivative reaction requires a tedious detection process. In this paper, a new method for the determination of optical purity of alkynes by chiral HPLC method is developed. The chiral alkynes were designed to coordinate with Co2(CO)8 in situ to form a stable chiral Co2(CO)6-aIkyne complex. The optical purity of the chiral alkynes was determined indirectly by liquid phase separation and analysis. The method is widely applied to alkynes without classical chromophore.
【学位授予单位】：山西师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.3

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