抗肿瘤天然活性产物松香烷内酯型大戟二萜的集群式不对称高效合成新策略研究

松香烷内酯型大戟二萜是从大戟属植物中提取的二萜类化合物，并且对多种肿瘤表现出很强的抑制活性，其中天然产物1-4是松香烷内酯型大戟二萜在结构上最具代表性的四类天然产物。本课题针对松香烷内酯型天然产物1-4设计了一条高效、通用的集群式不对称合成策略，从手性底物出发，通过关键的分子内oxa-Pauson−Khand反应快速构建四环骨架，然后利用共轭还原等策略对相关手性中心进行立体专一性地构筑，进而实现天然产物1-4的集群式不对称全合成，我们希望将该策略发展为合成松香烷内酯型二萜骨架的通用方法，为这类天然产物展开广泛的生物活性研究以及相关生物学构效关系研究奠定基础。

ent-Abietane diterpene lactones are isolated from the plants of Euphorbia and they exhibit potent anticancer activities for various tumor cells. From the structural viewpoint, natural products 1-4 are the most representative natural products of this family. Hence, we select the natural products 1-4 as the synthetic targets, and wish to develop an efficient and general route for collective asymmetric syntheses of natural products 1-4. Starting from the chiral compound, the crucial intramolecular oxa-Pauson-Khand reaction was employed to expeditiously construct the tetracyclic framework, and then serious methods, such as L-selectride conjugated reduction, were utilized to install the desired stereocenters. We wish to make this strategy become a general and practical synthetic process for ent-Abietane diterpene lactones and lay the good foundation of further biological evaluation of these natural products and structure-activity relationship (SAR) studies of their analogues.