Current investigations in our laboratory focus on the development of new synthetic methods and strategies, and their application in the total synthesis of natural products and biologically important compounds. A major thrust of our current research is the design and invention of new cycloaddition and annulation strategies for the synthesis of carbocyclic and heterocyclic compounds. Many of the methods under study involve the application of unusual molecules and highly reactive species as building blocks for the construction of important classes of organic compounds. We are particularly interested in the chemistry of highly unsaturated conjugated molecules (such as vinylketenes, iminoacetonitriles, conjugated enynes, and vinylallenes), and unusually strained molecules such as arynes, cycloalkynes, and cyclic allenes.
The utility of the methods under development is being tested and refined through their application in the total synthesis of biologically active natural products. Past accomplishments include the total synthesis of the antitumor antibiotic ascochlorin, the azulene antiulcer drug egualen sodium, and neurotoxic alkaloids isolated from poison dart frogs. Other studies focus on the synthesis of unusual polycyclic aromatic systems with novel electronic and spectroscopic properties. Finally, our laboratory has a longstanding interest in the development of environmentally benign methods for organic synthesis. In this connection, for example, we have studied the application of supercritical water and carbon dioxide as reaction media for organic synthesis and the development of metal-free synthetic reactions that minimize the formation of waste and byproducts.