杜鹃花科木藜芦烷二萜的全合成研究

The grayananoids are important members of the tetracyclic diterpenoids, which were found widely distributed in the plants of Ericaceae family as the characteristic secondary metabolites. Owing to their significant biological activities and unprecedented complex molecular architectures, the grayanane diterpenoids have attracted considerable interests from synthetic community for decades. In this proposal, we aim to develop a Ti(III)-catalyzed reductive cyclization/cyclopropane ring-cleavage cascade and an oxidative dearomatization-induced [5+2] cycloaddition/pinacol 1,2-acyl migration cascade, respectively, for the rapid construction of the unique bicyclo[3.2.1]octane carbon frameworks embedded in the grayanane diterpenoids. With the above reactions as key steps, two general strategies toward the asymmetric total syntheses of grayanotoxins I, III, V and XI will be explored accordingly with short steps and considerable efficiency. In the meantime, by incorporation of a Wagner-Meerwein rearrangement, a retro-Dieckmann fragmentation/vinylogous-Dieckmann cyclization cascade and a photosantonin rearrangement/intramolecular cycloetherification cascade, the asymmetric total syntheses of kalmanol and rhodomollanol A will also be investigated, which should shed some light on the biogenetic pathway of these two molecules.

作为四环二萜家族的重要成员，木藜芦烷二萜广泛分布于杜鹃花科植物中。由于显著的生物活性和新颖复杂的化学结构，其全合成研究具有重要学术价值和潜在应用前景。本项目拟分别发展Ti(III)催化的还原环化/环丙烷裂解串联反应和氧化去芳香化促进的[5+2]环加成/pinacol 1,2-酰基重排串联反应用于木藜芦烷二萜结构中独特双环[3.2.1]辛烷骨架的快速构建。在此基础上，拟以木藜芦毒素grayanotoxins I、III、V和XI为例，发展基于前述两类串联反应的普适性策略实现木藜芦烷二萜家族分子的简洁高效不对称合成。同时，拟结合Wagner-Meerwein重排反应、逆-Dieckmann裂解/插烯-Dieckmann环化串联反应和光促环己二烯酮重排/分子内环醚化串联反应分别完成kalmanol和rhodomollanol A的不对称全合成，为探究这两种分子骨架的生源合成途径奠定基础。

木藜芦烷二萜广泛分布于杜鹃花科植物中。由于显著的生物活性和新颖复杂的化学结构，其全合成研究具有重要学术价值和潜在应用前景。本项目围绕该类天然产物开展了系统性的全合成研究。针对其骨架特点，分别发展了氧化去芳香化促进的[5+2]环加成/pinacol 1,2-酰基重排串联反应以及Ti(III)介导的还原环化/环丙烷裂解串联反应，实现了木藜芦烷二萜结构中双环[3.2.1]辛烷核心骨架的快速构建。在此基础上，结合光促-山道年重排和Grob裂解/carbonyl-ene环化串联反应等关键转化，完成了包含Rhodomollanol A和Rhodomolleins XX/XXII等在内的木藜芦烷家族共计12个成员的集群式不对称全合成，其中9个为首次全合成。该研究工作不仅丰富了该类天然产物的合成化学，探明了其家族成员不同骨架之间的生源转化关系，也为深入研究其生物学功能奠定了坚实的基础。