钯催化烯丙位碳氢不对称氧化反应在天然产物Gonytolide C合成中的应用

发布时间：2018-08-23 11:22

【摘要】：色酮类化合物是具有重要生理活性的一大类天然产物,它们主要含有苯并吡喃结构,这类化合物一般具有抗细菌、抗真菌等生物活性。而含有苯并二氢吡喃酮丁内酯结构的Gonytolide系列天然产物则是其中具有代表性的一类化合物,它们是从真菌中分离得到的,既具有显著的促进先天免疫应答活性,又具有抗菌性和细胞毒性。由于这类化合物重要的潜在生理活性,迄今为止已有多篇文献报道了针对此类天然产物的不对称催化合成方法。钯直接活化烯丙位碳氢实现的烯丙位碳氢氧化反应是一类以简单烯烃作为原料的烯丙基化反应。通常传统的烯丙基化反应使用的烯丙基试剂含有各种离去基团,而直接活化烯丙位碳氢的方法则可以免去烯丙基试剂预先官能团化的步骤,不仅提高了合成效率,而且可以直接使用烯烃作为反应底物,扩展了底物的适用范围。最近我们课题组报道了用钯作为金属催化剂,手性亚磷酰胺作为配体,通过添加邻氟苯甲酸,使用苯醌类化合物作为氧化剂,以很好的对映选择性和收率高效地构建了含有季碳手性中心的苯并二氢吡喃骨架。在此基础上,我们采用了这种钯催化的烯丙位碳氢不对称氧化的策略构建了天然产物Gonytolide C的骨架结构。通过逆合成分析法,我们尝试了环氧化、光反应、硒溴促进的内酯环化和双羟化等多种不同的合成路线,但是发现只有双羟化反应可以比较有效地构建苯并二氢吡喃酮的丁内酯结构,最终我们以92%ee的对映选择性完成了天然产物Gonytolide C的形式不对称合成。
[Abstract]:Chromatic ketones are a kind of natural products with important physiological activities. They mainly contain benzopyran structure. These compounds generally have anti-bacterial and anti-fungal biological activities. The series of natural products of Gonytolide containing benzodihydropyranone butyrolactone are representative compounds. They are isolated from fungi and have significant innate immune response activity. It also has antibacterial and cytotoxic properties. Because of the important potential physiological activity of this kind of compounds, many literatures have reported the asymmetric catalytic synthesis methods for this kind of natural products. The direct activation of allyl hydrocarbon by palladium is a kind of allylation reaction using simple olefin as raw material. The conventional allyl reagents used in allylation reactions usually contain a variety of departure groups, while the direct activation of allyl hydrocarbons can avoid the step of prefunctionalization of allyl reagents, which not only improves the synthesis efficiency, but also improves the synthesis efficiency of allyl reagents. Moreover, olefin can be used as the reaction substrate directly, which extends the application range of the substrate. Recently, we reported that palladium was used as metal catalyst, chiral phosphorous amide as ligand, benzoquinone as oxidant by adding o-fluorobenzoic acid. The benzodihydropyran skeleton containing the chiral center of quaternary carbon was constructed with good enantioselectivity and yield. On this basis, the framework structure of natural product Gonytolide C was constructed by using this palladium catalyzed asymmetric oxidation strategy of allyl hydrocarbon. By inverse synthetic analysis, we have tried many different synthetic routes, such as epoxidation, photoreaction, seleno-bromine promoted lactone cyclization and dihydroxylation, etc. However, it was found that only the dihydroxylation reaction could effectively construct the butyrolactone of benzodihydropyranone. Finally, we completed the asymmetric synthesis of natural product Gonytolide C with enantioselectivity of 92.
【学位授予单位】：中国科学技术大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.251

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