Towards the Total Synthesis of Pl-3: Preparation of the Eastern Fragment through a Diastereoselective SmI(2)-Mediated Reformatsky Reaction

The jatrophane diterpene Pl-3, isolated in 2003 from Euphorbia platyphyllos, is a structurally complex natural product with highly promising biological properties that include pronounced antiproliferative activity and the inhibition of the efflux-pump activity of multidrug resistance p-glycoprotein. Herein, the synthesis of the eastern fragment of Pl-3 is outlined. The target compound is synthesized in nine synthetic operations in good overall yield, starting from readily available d-ribose. The key step in the preparation of the eastern part of Pl-3 is a diastereoselective SmI(2)-mediated Reformatsky reaction. The proposed route is highly flexible and could also be applied to the synthesis of structurally related jatrophane diterpenes.