Total Synthesis of (±)- and (+)-Euphohyrisnoid A

The first total synthesis of (±)- and (+)-euphohyrisnoid A, a highly rearranged lathyrane Euphorbia diterpenoid with a new [5-7-6-6] tetracyclic core, was accomplished. The synthesis was strategically guided by a mild intramolecular Diels-Alder (IMDA) reaction, which efficiently constructed the pivotal bicyclo[2.2.2] ring system with high diastereoselectivity. This outcome experimentally validated prior quantum mechanical calculations. The IMDA precursor was assembled efficiently via a Tsuji-Trost reaction. The desired seven stereocenters, including two quaternary stereocenters in the final product, were constructed diastereoselectively.