Total Synthesis of Jatrophane Diterpene Euphosalicin

Euphosalicin was isolated from Euphorbia salicifolia, a plant which is native to Central Europe, eastern Central Europe. The complex trans-bicyclo[11.3.0] ring system of euphosalicin together with highly functionalized five-and thirteen membered ring and eight stereogenic centers present considerable challenge for total synthesis. Additionally, this compound was found to have extremely high levels of MDR-reversal activity and can serve as potential lead structure for drug development. Since natural sources afford very small quantities of euphosalicin and no total synthesis is available so far, a synthetic access for further biological studies is inevitable. The goal of this project is enantioselective total synthesis of euphosalicin which should allow the preparation of enough material for detailed investigation of its biological activity and the synthesis of simplified substrates for structure-activity relationship (SAR) studies.