Stereochemical characterization of the diastereomers of the phenobarbital N-beta-D-glucose conjugate excreted in human urine.

The absolute configuration of the N-beta-D-glucoside metabolites of phenobarbital was determined by methylation of the diastereomers to make mephobarbital N-beta-D-glucosides, followed by oxidative removal of glucose to give the optical isomers of mephobarbital. Following a single oral dose of phenobarbital to two male subjects, both phenobarbital N-beta-D-glucosides were excreted in the urine. The absolute configuration (C-5 position) of the major phenobarbital N-beta-D-glucoside excreted in the urine was the S form. A pronounced stereoselective formation and/or urinary excretion occurs for the N-glucoside conjugates of phenobarbital in humans.