Conformationally defined aromatic amino acids. Synthesis and stereochemistry of 2-endo- and 2-exo-amino-1,2,3,4-tetrahydro-1,4-ethanonaphthalene-2-carboxylic acids (2-endo- and 2-exo-aminobenzobicycle[2.2.2]octene-2-carboxylic acids).
The synthesis of the title compounds 1a and 1b has been accomplished in good yield by conversion of ketone 3 to the corresponding hydantoins 4a and 4b via a Bucherer-Bergs reaction, followed by barium hydroxide hydrolysis. The stereochemical assignments of the intermediate hydantoins 4a and 4b and the ethyl ester hydrochlorides 5a and 5b were determined by H NMR analysis. Attempts toward the synthesis of 2-amino-1,4-dihydro-1,4-ethanonaphthalene-2-carboxylic acid isomers 2a and 2b utilizing the pathway discussed for 1a and 1b led only to products arising from a retro-Diels-Alder reaction. Preliminary screening of 1a and 1b as inhibitors of phenylalanine hydroxylase (PH) and phenylalanine decarboxylase (PAD) is also discussed. The use of the benzobicyclo[2.2.2]octene nucleus for the construction of conformationally defined analogues of important medicinal agents is rationalized, and the title compounds are compared to several other conformationally defined systems. The title compounds represent conformationally defined models of the lower energy conformations of alpha-methylphenylalanine.
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis*; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors; D013293:Enterococcus faecalis / Q000201:enzymology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008968:Molecular Conformation; D010649:Phenylalanine / Q000037:antagonists & inhibitors; D010651:Phenylalanine Hydroxylase / Q000037:antagonists & inhibitors; D013237:Stereoisomerism
D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase; D002262:Carboxy-Lyases; C019517:phenylalanine decarboxylase