Euphorbiaceae Diterpenes - Total Synthesis of Euphosalicin

Several terpenes isolated from plants of the Euphorbiaceae family display highly interesting biological properties, including antiviral, antibacterial and antitumor activities. Although Euphorbiaceae constituents can be considered as potential drug candidates, synthetic efforts toward those highly interesting natural products are scarce. A concise total synthesis of euphosalicin, a diterpene isolated from Euphorbia salicifolia is described. Euphosalicine displays a high level of multi-drug resistance reverse effect and can therefore be considered as a possible drug for cancer chemotherapy. The synthesis described in this proposal should also allow easy access to other biological active Euphorbiaceae constituents and might therfore be employed in structure activity relationship studies. Key steps in the synthesis are a Hetero-Diels-Alder reaction with singlet oxygen for the introduction of the oxygenation pattern of the functionalized cyclopentane segment of the natural product as well as an asymmetric ester-enolate Clasien rearrangement, Nozaki-Hiyama-Kishi coupling and pinacol coupling for the final ring closure reaction.

Several terpenes isolated from plants of the Euphorbiaceae family display highly interesting biological properties, including antiviral, antibacterial and antitumor activities. Although Euphorbiaceae constituents can be considered as potential drug candidates, synthetic efforts toward those highly interesting natural products are scarce. A concise total synthesis of euphosalicin, a diterpene isolated from Euphorbia salicifolia is described. Euphosalicine displays a high level of multi-drug resistance reverse effect and can therefore be considered as a possible drug for cancer chemotherapy. The synthesis described in this proposal should also allow easy access to other biological active Euphorbiaceae constituents and might therfore be employed in structure activity relationship studies. Key steps in the synthesis are a Hetero-Diels-Alder reaction with singlet oxygen for the introduction of the oxygenation pattern of the functionalized cyclopentane segment of the natural product as well as an asymmetric ester-enolate Clasien rearrangement, Nozaki-Hiyama-Kishi coupling and pinacol coupling for the final ring closure reaction.