Abstract
Kaitocephalin was isolated from a filamentous fungus Eupenicillium shearii PF1191 by Seto and Shin-ya et al. by the screening for novel AMPA/KA antagonist employing chick telencephatic neurons. Kaitocephalin suppressed kainate excitotoxicity in this assay (EC50 = 0.68 M) and exhibited lower cytotoxicity against these neurons (>500 M). Therefore, kaitocephalin has been promising to be a potent lead compound for development of therapeutic agents toward various ischemia-reperfusion injuries such as stroke and epilepsy. Three groups including our group have succeeded in the total synthesis. However, it still required a practical synthetic approach that enables to supply sufficient amounts of natural product and its structurally related analogs for the neurobiological assays. We describe the highly efficient total synthesis of kaitocephalin and its analogs based on the diastereoselective coupling of A, B, and C, and their structure-activity relationship study.
