Our research centers on the total synthesis of complex natural products and rationally designed molecular probes and their application to biological problems, especially in neuroscience. A large part of our research program is dedicated to the synthesis and biological evaluation of natural products - that is biologically active metabolites with relatively low molecular weights. We are convinced that the majority of natural products have not yet been found and that a wealth of interesting chemistry and biology awaits discovery. As synthetic organic chemists, we are intrigued by the structural beauty and functional sophistication of natural products. Through the power of total synthesis, we gain insight into their structure/activity relationships and biosynthetic origin. In addition, the total synthesis of complex natural products provides an ideal platform for the invention or discovery of new synthetic methodology or the validation of modern reactions in a complex environment.
Along with our studies on natural products, we are concerned with the chemical biology of neural systems. Neuroscience is indeed one of the most exciting scientific frontiers of our time. As its molecular foundation becomes established, this field is currently undergoing the same transformation that has propelled genetics to the forefront of science and has ultimately led to the elucidation of the human genome. Until recently, progress in the neurosciences has been hampered by a lack of structural understanding of the basic components that underlie the function of excitable cells: the ionotropic receptors, i.e. ion channels, and the metabotropic receptors, i.e. G-protein coupled receptors. With the emergence of the first X-ray crystal structures of these proteins, this situation has changed dramatically and neurobiology is bound to mature into a truly molecular science. We believe that the time has come for organic chemists, who have a keen understanding of structure and mechanism and the ability to synthesize complex molecules, to make an impact on this field. Our current focus lies on the functional reengineering of ion channels by attaching synthetic switches that respond to a diverse array of input signals. These manipulated ion channels can be inserted into excitable cells, e.g. neurons, and can render them sensitive to new stimuli, e.g. light.
For more information see our publication list, and check out our list of completed synthetic targets.