The principal scientific goal for the proposed research is to develop efficient methodology for the synthesis of polycyclic cyclooctane-containing ring systems many of which have considerable therapeutic potential. The proposal aims to investigate the scope and limitations of a sequential 6-exo dig cyclization/Claisen rearrangement process as the key strategy in cyclooctanoid ring synthesis. Potentially, this strategy provides access to a large number of different cyclooctanoid structures found in several biologically active natural products. Among the class of natural products targeted are the fusicoccins, a large family of diterpenoid compounds that possess a wide range of significant biological activity, including anti-cancer, antibacterial and antifungal activity. The fusicoccanes and several other cycloctanoid natural products, such as the ophiobolins, are characterized by a fused 5-8-5 tricyclic core, which should be readily accessible by the strategies outlined in this proposal. Thus, the molecular targets pursued in the proposed work hold considerable potential as valuable lead compounds for the development of novel agents to treat human diseases, including cancer as well as bacterial and fungal infections.
The molecular targets pursued in the proposed work hold considerable potential as valuable lead compounds for the development of novel agents to treat human diseases, including cancer as well as bacterial and fungal infections.
