Palladium (II)-catalyzed olefin-coupling reactions of kainic acid: effects of substitution on the isopropenyl group on receptor binding.
Two palladium-catalyzed carbon-carbon bond forming reactions were found to be useful for the modification of a protected amino acid derivative containing a sterically hindered isopropenyl group. Arylation of the terminal methylene group of the dimethyl ester of N-(ethoxycarbonyl)kainic acid (3) was accomplished by treatment with an aromatic amine, palladium(II) acetate, and tert-butyl nitrite. Substitution of the allylic methyl group of 3 was accomplished by conversion to the pi-(allyl)palladium complex (5) which, on subsequent treatment with the carbanions of tert-butyl acetoacetate or phenylthioacetone, gave the alkylated products. Both the (Z)- and (E)-3-nitrophenyl derivatives (8a,b) of kainic acid were active in the standard binding assay. Unexpectedly, the cis compound in the nitrophenyl series (8a), which more closely resembles the extended conjugation found in domoic acid, was found to be 20 times less potent than the trans derivative 8b. The latter had one-fifth the receptor-binding affinity of kainic acid.
D000818:Animals; D001681:Biological Assay; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D010165:Palladium; D011759:Pyrrolidines / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013329:Structure-Activity Relationship
D007608:Kainic Acid; D010165:Palladium; D011759:Pyrrolidines; D011956:Receptors, Cell Surface; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter