Synthesis of a small library of (-)-dysiherbaine analogs as ionotropic glutamate receptor ligands

AEI 91

Stephen A. Habay, sahabay@gmail.com and A. Richard Chamberlin. Department of Chemistry, University of California-Irvine, Irvine, CA 92697
In our continuing efforts to develop small molecule probes for the ionotropic glutamate receptors (iGluRs) we have synthesized a small library of restricted glutamate analogues based upon the structure of the natural product (-)-Dysiherbaine. This potent glutamate receptor agonist provides a biologically validated starting point for library design. Elucidating the complex interactions of iGluR subtypes with small molecules is a high priority not only because of their ubiquitous functions in normal CNS processes such as fast synaptic transmission, learning and memory, but also their role in pain, cognitive impairment and neurodegenerative disorders such as Alzheimer's disease. There is currently a large interest in designing sub-type selective agonists and antagonists of iGluRs as leads for therapeutic agents. The synthesis of our small library of compounds and their biological evaluation is presented.