Total Synthesis of (+)-Coriamyrtin via a Desymmetric Strategy of a 1,3-Cyclopentanedione Moiety

This paper describes the total synthesis of (+)-coriamyrtin, a picrotoxane-type sesquiterpene. The natural product is widely known as a neurotoxin of the Coriariaceae family and bears a highly functionalized cis-hydrindane skeleton. Despite being biologically and synthetically attractive molecule, only two examples of the total synthesis are reported to date. Our synthetic strategy involves the highly stereoselective construction of the cis-hydrindane skeleton via the desymmetric strategy of a 1,3-cyclopentanedione moiety using an intramolecular aldol reaction and elaborate functionalization of the cyclopentane ring in the bicyclic structure for the formation of the 1,3-diepoxide moiety of coriamyrtin. Our method could be applied to synthesize various natural products with similar bicyclic skeletons and to expand neurobiological studies using synthesized products.