Our research is centered on the development of new synthetic methods and the utilization of synthetic chemistry for the study of important biological and medical problems. The projects in our laboratory range from the development of new methods in organic synthesis and the total synthesis of biologically important natural products to medicinal chemistry around leads compounds. We do a significant amount of work in collaboration with biomedical researchers in the Houston/Galveston area. Many of our projects provide us with a unique opportunity to test the biological activity of our compounds and make modifications to improve activity or test important biological principles. Some of the projects we are currently working on are:
Development of Chemistry for Small Molecule Library Synthesis
Combinatorial chemistry is a valuable tool for the discovery of new drug candidates. The ability to synthesize hundreds of compounds for screening is a useful complement to rational drug design. We are developing general approaches for the synthesis of a variety of organic structures. These molecules will then be screened for biological activity often in collaboration with colleagues. Some of the biological areas we are developing libraries for are the investigation of anti-viral, anti-cancer, anti-malaria compounds and inhibitors of anthrax edema factor. Total Synthesis and Medicinal Chemistry of
Biologically Important Natural Products
We have begun the total synthesis of a number of natural products that possess important biological activity. Our approaches are designed to not only provide the natural product but also to allow for significant modification around a target's basic scaffold. Two systems we are currently working on are Salvinorin A and Dysiherbaine.
Rhodium Catalyzed Synthesis of Medium Sized Rings
In the area of synthetic methods development, we are working on new reagents to form multiple carbon-carbon bonds in one reaction. One example of such a reaction is a rhodium catalyzed [4+2+2] reaction we have invented. In this case a dieneyne and an alkyne are combined, under rhodium catalysis, to form a new cyclooctatriene. This chemistry is currently being developed for other unsaturated systems and the synthesis of natural products including asteriscanolide.
Peptide Based Catalysts
Much is known about the three-dimensional structure of peptides. In one project we are using the structural features of these molecules in the de novo design of unnatural enzymes. By designing and building peptides that possess the ability to bind catalytically active transition metals we are developing new types of catalysts. We are taking two approaches to this problem. One method is to synthesize unnatural amino acids, and then by solution phase, solid phase or combinatorial synthesis techniques, build peptides of moderate length. The other route is via the modification of naturally occurring proteins. Proteins that contain unnatural metals have a number of potential uses. In addition to being entirely new types of catalysts, they should be of use as radio-imaging agents, as site-specific DNA cleavage agents and as catalytic enzyme inhibitors.