Synthetic Study on Picrotoxane-type Sesquiterpenoids: Background of the Project Idea and Process of Completion in the Total Synthesis of Coriamyrtin

Picrotoxane-type sesquiterpenoids are a family of more than one hundred natural products, which bear a picrotoxane skeleton as the common structure. Among them, strong neurotoxic compounds, picrotoxinin, coriamyrtin, and tutin, have paid much attention from organic researchers as well as neuroscience researchers since the 1900’s. However, because almost all of the picrotoxane skeletons in the natural products are highly functionalized, the total synthesis of such natural products is challenging. This paper describes a method to stereoselectively synthesize the cis-fused 5,6-ring framework contained in the picrotoxane skeleton. A desymmetric strategy of the 2-methyl-1,3-cyclopentanedione moiety via the proline-mediated intramolecular aldol reaction provided the desired cis-fused skeleton. In addition, the total synthesis of coriamyrtin was achieved through the elaborate functionalization of the cyclopentane ring in the 5,6-ring framework obtained under our established intramolecular aldol reaction conditions.