pedrolide的全合成研究

复杂天然产物pedrolide分离于大戟科植物Euphorbia pedroi Molero and Rovira，是一种具有新颖骨架和抗多重耐药性活性的二萜。该分子具有六个紧凑的环系，包括高张力的[2.2.1]庚烷骨架和6/3并环结构，结构上高度氧化，且具有12个连续的手性中心（其中包括3个季碳）。该分子具有很大的合成挑战性，至今还没有合成报道。因此，开展pedrolide的合成研究具有重要的学术意义。.本项目致力于发展一种高效简洁的合成路线，用于快速构建pedrolide的六环核心骨架，拟通过新颖的环戊二烯参与的分子内Diels-Alder反应一步构建三环[2.2.1]庚烷骨架，随后采用独特的环丙烯酮参与的Robinson成环反应实现6/3并环的组装，接着通过氧杂的1,4-加成反应完成内酯环的构建。最后，以13步总步数实现pedrolide的高效不对称全合成，并进一步研究其生物活性。

Pedrolide, a complex diterpenoid isolated from Euphorbia pedroi Molero and Rovira, containing an unprecedented skeleton along with novel reversed multidrug resistance bioactivity. It is compacted with six rings bearing a bicyclo[2.2.1]heptane system and a 6/3-fused ring system. The skeleton is highly oxidized and in possession of 12 contiguous stereocenters including 3 quaternary centers. It stands as a significant synthetic challenge and no total synthesis has been reported yet. Therefore, it is meaningful to study its total synthesis..This project is dedicated to developing an efficient synthetic route to assemble the skeleton of pedrolide. A novel intramolecular Diels-Alder reaction was proposed to form the bicyclo[2.2.1]heptane system, the remaining 6/3-fused ring system is then assembled through a unique Robinson annulation using cyclopropene, subsequent oxa-1,4-addition furnished the lactone moiety. Finally, the asymmetric total synthesis of pedrolide is completed efficiently in 13 steps. Also, we will further investigate its bioactivity.