天然产物Chlorahololides和Chlorajapolides 的全合成研究

Both Chlorahololides and chlorajapolides are isolated from South China Chloranthus holostegius with highly complex sesquiterpenoid dimer.Chlorahololide A, a lindenane-type sesquiterpenoids dimer, has shown to exhibit potent and selective inhibition of the potassium channels.The unique structural features and interesting biological activity render chlorahololides very attractive and challenging target for total synthesis.However, to the best of our knowledge, there have no total synthesis been described to date. This project will focus on fine-tuning the stero- and chemical slectivities, and developing an efficient and concise total synthesis approach. A biomimetic strategy was taken for its total synthesis of chlorahololide A, which may be assembled by two segments . Sequential biomimetic elaborations, featured by using biomimetic synthesis strategy and convergent route via a key D-A reaction, selective oxidation and rearrangement reacton etc., ensured the concise total synthesis of chlorahololide A.

Chlorahololides和chlorajapolides 是从陆生金粟兰属(科)植物中分离得到倍半萜类化合物。其中Chlorahololide A (1)是一种结构新颖、高度复杂的倍半萜的二聚体。Chlorahololide A (1)具有高选择性的钾离子通道抑制作用。到目前为止，Chlorahololide A (1)的全合成还未见报道。本课题在此类复杂分子合成中探索立体和化学选择性的调控、发展高效、简洁的化学全合成方法，从而为这类药用资源天然产物的获取及其药理的构效关系研究提供化学合成途径和物质基础。具体合成方面而言采取仿生合成的策略，将Chlorahololide A (1)断开为两个二倍半萜的片段，使用汇聚式的合成路线、关键的D-A环加成反应以及选择性氧化以及重排反应完成这类天然产物目标分子全合成。

Chlorahololides 和chlorajapolides 是从陆生金粟兰属(科)植物中分离得到倍半萜类化合物。其中Chlorahololide A (1)是一种结构新颖、高度复杂的倍半萜的二聚体。Chlorahololide A (1)具有高选择性的钾离子通道抑制作用。到目前为止，Chlorahololide A (1)的全合成还未见报道。本课题在此类复杂分子合成中探索了立体和化学选择性的调控、发展高效、简洁的化学全合成方法，从而为这类药用资源天然产物的获取及其药理的构效关系研究提供化学合成途径和物质基础。具体合成方面而言采取仿生合成的策略，使用汇聚式的合成路线、关键的D-A 环加成反应以及选择性氧化以及重排反应等关键反应，完成了这类金粟兰属内酯天然产物若干目标分子全合成。