SYNTHESIS OF A NEW KAINIC ACID-BASED SELECTIVE LIGAND AS A POTENTIAL PHOTOAFFINITY LABEL OF NON-NMDA EXCITATORY AMINO-ACID RECEPTORS IN CHICKEN BRAIN

The synthesis of two analogues of kainic acid (KA) incorporating photo -activatible moieties attached either on the gamma-carboxy function (g amma-amide 1) or the isopropenyl side-chain (amide 2) is described. Th e synthesis of the former amide involves coupling of N-(tert-butoxycar bonyl)-protected alpha-diphenylmethyl kainate with 2-(4-azidobenzamido )ethylamine (5) followed by trifluoroacetic acid mediated complete dep rotection. Amide 2 was synthesized by palladium-mediated allylic amina tion, with 4,4'-dimethoxybenzhydrylamine (DMBA), of N-(9-fluorenylmeth oxycarbonyl)-protected dimethyl kainate, followed by splitting the DMB -group with formic acid, coupling with N-hydroxysuccinimidoyl 4-azidob enzoate and finally complete deprotection by saponification. Prelimina ry pharmacological studies in chicken brain membranes showed that amid e 2 is a stronger inhibitor of [H-3]KA binding on chicken cerebellar m embranes than is amide I and that amide 2 has specificity only for the cerebellar, as opposed to the telencephalon, type of non-NMDA binding sites.