Asymmetric Total Synthesis of Arcutinidine, Arcutinine, and Arcutine

We have accomplished the asymmetric
total synthesis of arcutinidine,
arcutinine, and arcutine, three arcutine-type C20-diterpenoid alkaloids.
A pentacyclic intermediate was rapidly assembled by using two Diels–Alder
reactions. We developed a cascade sequence of Prins cyclization and
Wagner–Meerwein rearrangement to construct the core of arcutinidine,
which was then elaborated into an oxygenated pentacycle through a
scalable route. Chemoselective reductive amination followed by spontaneous
imine formation furnished the pyrroline motif in the final stage.
We clarified the S configuration of the α-carbon
of the acyl group within arcutine through chemical synthesis and crystallographic
analysis.

我们成功完成了阿枯米定（arcutinidine）、阿枯米宁（arcutinine）与阿枯亭（arcutine）这三种阿枯亭型C20-二萜类生物碱的不对称全合成。本研究通过两步狄尔斯-阿尔德（Diels–Alder）反应快速构建了五环中间体；我们开发了普林斯环化（Prins cyclization）与瓦格纳尔-米尔魏因重排（Wagner–Meerwein rearrangement）的串联反应序列，用以构筑阿枯米定的核心骨架，随后通过可放大合成路线将其转化为含氧五环结构。经化学选择性还原胺化结合自发亚胺生成的步骤，我们在最终阶段得到了目标分子中的吡咯啉结构基元。此外，我们通过化学合成与晶体结构分析，明确了阿枯亭中酰基α-碳原子的S构型。