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. Target molecules currently under investigation, and proposed target molecules for future research include quadrone, laurenene, the pentalenolactones, carbacyclins, and hydrazulenes. These molecules display a wide range of biological activity and include antibiotics, cytotoxics and anti-cancer agents, and therapeutic agents for circulatory disorders. The methodology to be used is derived from the organometallic cycloaddition processes which have been highly successful in the past at permitting synthetic schemes to bypass much conventional synthetic methodology. The current state of the art permits prediction of success with considerable confidence. This proven methodology is proposed to be supplemented with several new concepts that, taken together, are aimed at addressing those situations in which the methodology does not succeed satisfactorily, and at modifying the existing procedures to permit ready access in a practical way to the desired target molecules in optically active form. The overriding goal of the proposed research will be to generate methodology derived from unique new combinations of several technologies, to permit access to molecules of biomedical importance in their most biologically active forms, as efficiently as possible from readily available materials.