This research program focuses on developing novel and efficient syntheses of two structurally distinct classes of diterpenes employing related tactics and strategies. The structurally complex tumor-promoting diterpenes, ingenol and phorbol are known to be potent bioactive compounds when appropriately derivatized. Ingenol esters have been shown to display promising apoptosis induction activity as well as the better known tumor-promoting characteristics. The unifying feature of our research program is that both of these targets can be synthesized employing closely related starting materials and similar """"""""strategy level"""""""" transformations. Despite the apparent structural diversity of these natural products we plan to prepare each starting from a higher-order cycloaddition that assembles, in one operation, the bulk of each target's structural features. This """"""""unified"""""""" approach into ingenol and phorbol will employ a common advanced intermediate that is diverted toward the two targets at a relatively late stage in the synthetic sequence. These projected investigations should generate substantial new knowledge about complex synthesis as well as providing additional insight into some of the bioactivity exhibited by the subject natural products.
| Rigby, James H; Bazin, Berangere; Meyer, J Hoyt et al. (2002) Synthetic studies on the ingenane diterpenes. An improved entry into a trans-intrabridgehead system. Org Lett 4:799-801 |
