Abstract

Solution conformations of 5-ethyl-5-(1'-methylbutyl)-, 5-ethyl-5-(1',3'-dimethylbutyl)-, and 5-ethyl-5-(1',3',3'-trimethylbutyl)barbituric acids in a variety of solvents have been studied by nuclear magnetic resonance techniques. Implications of the results obtained in this study for discrimination between the enantiomers of 5-ethyl-5-(1',3'-dimethylbutyl)barbituric acid [R-(+), excitatory, and S-(-), depressant] at the excitatory receptor site are discussed. It is suggested that discrimination between the enantiomers is based primarily on a required binding orientation of the pyrimidinetrione ring and differing aliphatic side chain geometries resulting from a strong conformational preference of the isopropyl termini.