Total Synthesis of Nineteen-Carbon Picrotoxane Terpenoid Picrodendrin L

Nineteen-carbon picrotoxane terpenoids are a class of structurally more complicated and biologically more potent natural products than 15-carbon picrotoxane terpenoids. Nevertheless, no total synthesis of this subfamily of picrotoxane terpenoids has been reported. Here, we describe the first total synthesis of a 19-carbon picrotoxane terpenoid─picrodendrin L. The central cis-bicyclo[4.3.0]nonane core structure of picrodendrin L was efficiently constructed through a Danheiser cyclopentene synthesis reaction employing highly functionalized carvone and allene derivatives. The bridged lactone moiety was forged via Ma's oxidation protocol, and the spirolactone ring was synthesized by a halolactonization. The last two carbons were efficiently introduced through an aldol reaction of an advanced lactone substrate with acetaldehyde. The appropriate oxidation states of picrodendrin L were carefully adjusted along the synthetic route. The first total synthesis of picrodendrin L paves the way for the total synthesis and in-depth biological evaluation of other members of 19-carbon picrotoxane terpenoids.