This proposal describes the continuation of a project that involves the synthesis of biologically active molecules containing, or derived from molecules containing the cyclopentenone ring system. During the current grant period we have greatly expanded both the scope and our mechanistic knowledge of the organometallic reaction utilizing dicobalt octacarbonyl to promote cocyclization of alkenes, alkynes, and carbon monoxide. A number of synthesis that are either completed or in progress illustrate the enormous power of this method in bypassing conventional routes to molecules containing this ring system. Proposed target molecules for future research include triquinane- derived systems, guaianolides and pseudoguaianolides, and heterocycles, including terpene alkaloid. These materials display a wide range of biological activity and include antibiotics, antiviral, cytotoxics, and anti-cancer agents. The proposed work is designed to further critically test the limits of this methodology, as well as to make available new synthetic routes to these important classes of compounds, routes that involve a minimal number of reaction steps from inexpensive and readily available starting materials.