Daphnicyclidin F is a structurally unprecedented hexacyclic alkaloid isolated from the stems of the Japanese trees Daphniphyllum humile and teijsmanni. The natural product shows strong cytotoxic activity against both routine lymphorna L1210 cells and human epidermoid carcinoma KB cells. The planned synthetic route will not only efficiently provide additional quantities of the natural product for more extensive pharmacological evaluation but also will give ready synthetic access to other members of this unique family of alkaloids. The synthetic route is also amenable to analog synthesis and will allow the active pharmacophore of the natural product to be explored, A novel method for alkoxy-fulvene synthesis will be developed which may be applied to other natural products containing this functionality. Existing reactions wilt be applied to complex systems, and the knowledge gathered in this process will expand the limits of the current methodology available to organic chemists. ? ?
| Williams, David R; Reeves, Jonathan T; Nag, Partha P et al. (2006) Studies of the generation and pericyclic behavior of cyclic pentadienyl carbanions. Alkylation reactions as an efficient route to functionalized cis-bicyclo[3.3.0]octenes. J Am Chem Soc 128:12339-48 |
| Williams, David R; Reeves, Jonathan T (2004) Carbolithiation for the generation of cyclooctadienyl anions and tandem electrocyclization/alkylation to functionalized cis-bicyclo[3.3.0]octenes. J Am Chem Soc 126:3434-5 |
