Inhibition of pig kidney L-aromatic amino acid decarboxylase by 2,3-methano-m-tyrosines.
Both racemic (E)- and (Z)-2,3-methano-m-tyrosines (9E and 9Z) have been synthesized from a common intermediate, monoester (Z)-1-(ethoxycarbonyl)-2-[3-[(2-methoxyethoxy)methoxy]phenyl] cyclopropanecarboxylic acid (5). Quinine and ephedrine, respectively, were used to resolve their N-tert-butoxycarbonyl (Boc) derivatives. Among the compounds prepared, the (+)-(E)-diastereomer of 9 is the most potent inhibitor of L-aromatic amino acid decarboxylase (Dopa decarboxylase), having a Ki of 22 microM, with the (-)-Z-diastereomer (9Z) second at Ki = 49 microM. (+)-9E is a 45-fold more potent inhibitor of DDC than its acyclic analogue, D-m-tyrosine.
Ahmad
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S
Department of Chemistry, School of Chemical Sciences, University of Georgia, Athens 30602.
Phillips
R S
RS
Stammer
C H
CH
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002851:Chromatography, High Pressure Liquid; D004296:Dopa Decarboxylase / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013552:Swine; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004791:Enzyme Inhibitors; C074204:2,3-methano-3-tyrosine; D014443:Tyrosine; D004296:Dopa Decarboxylase