Absolute configuration of the major metabolite of 5,5-diphenylhydantoin, 5-(4'-hydroxyphenyl)-5-phenylhydantoin.
Chemical conversions, optical comparisons, and chiroptical measurements (CD) were employed to determine the absolute configuration of the enantiomers of 5-(4'-hydroxyphenyl)-5-phenylhydantoin (HPPH) (1b and 1c). Studies on a key intermediate, (-)-2-cyclohexyl-2-phenylglycine (5b), led to the reexamination of the well-known rule of Clough-Lutz-Jirgensons. Optical comparisons by means of derivatization into hydantoins and 3-phenyl-2-thiohydantoins (application of Freudenberg's rule of shift) gave conclusions which were consistent with chiroptical measurements on the above compounds. Thus, (-)-HPPH (1c), the major metabolite of 5,5-diphenylhydantoin in man, has the S configuration. This assignment was confirmed by X-ray single-crystal structure analysis of (+)-HPPH 10-(+)-camphorsulfonate (18b).
D002942:Circular Dichroism; D008968:Molecular Conformation; D009904:Optical Rotation; D009905:Optical Rotatory Dispersion; D010672:Phenytoin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism; D013237:Stereoisomerism; D014961:X-Ray Diffraction
D010672:Phenytoin