Divergent Syntheses and Biological Evaluations of New ArtificialGlutamate Analogs

摘要

(2R)-IKM-159,a hybrid of two neuroactivenatural products (dysiherbaine and kainic acid),wasdesigned and synthesized in our laboratory.1Reasonably,IKM-159 was later identified as anantagonist selective to subtypes of AMPA-typeionotropic glutamate receptor.To study the structure-activity relationships,and to develop probes for thereceptor,we synthesized new analogs (TKM-50,TKM-86,TKM-99) bearing dioxane ring forthe C-ring by the novel three-component oxa-Michael reaction.