Syntheses of trans-3′-substituted-CCG-IV analogs and their characterization to ionotropic glutamate receptors

Trans-3′-substituted-CCG-IV analogs (2 and 3) were efficiently synthesized via an intramolecular cycloaddition of diazoacetamide 4a using a chiral rhodium catalyst. These analogs evoked marked depolarization through ionotropic glutamate receptors on the spinal motoneurons or the kainate-sensitive dorsal root C-fiber of new born rats even though their binding affinities for the receptors on rat brain synaptic membranes were relatively low. These results suggest that the depolarizing action on C-fiber is not caused by the activation of kainate high affinity sites.