Cyanthiwigin diterpenoids are known to display antituberculosis and anticancer activity. Recently, cyanthiwigin AC was isolated, but not in sufficient quantities for pharmaceutical evaluation. This proposal outlines the asymmmmetric total synthesis of Cyanthiwigin AC. Cyanthiwigin AC serves as an excellent scaffold to explore new catalytic asymmetric methodology and to expand upon existing enantioselective reactions. New reactivity will be explored through the use of an asymmetric Diels-Alder reaction with a hydrazine- or diazene-substituted diene. The resulting Diels-Alder adduct can then be used to transfer chirality and enables rapid access to new substitution patterns. The key step of the synthesis is a palladium mediated Heck cascade to diastereoselectively set a spiro-ring quaternary center and to set a 5,6 cis fused skeleton. The stereo selective and convergent route will provide an efficient synthesis of cyanthiwigin AC as well as access to potentially bioactive synthetic analogs.
| Xie, Hao; Sammis, Glenn M; Flamme, Eric M et al. (2011) The catalytic asymmetric Diels-Alder reactions and post-cycloaddition reductive transpositions of 1-hydrazinodienes. Chemistry 17:11131-4 |
| Sammis, Glenn M; Flamme, Eric M; Xie, Hao et al. (2005) Design, synthesis, and reactivity of 1-hydrazinodienes for use in organic synthesis. J Am Chem Soc 127:8612-3 |
