Synthesis of N-β-D-glucopyranosyluronate derivatives of barbital, phenobarbital, metharbital, and mephobarbital

Article abstract of DOI:10.1016/0008-6215(94)00358-M

The synthesis and characterization of barbital, phenobarbital, metharbital, and mephobarbital glucouonides, is reported.The condensation of per(trimethylsilyl)-barbital and -phenobarbital with methyl 1,2,3,4-tetra-O-acetyl-β-D-glucopyranuronate in the presence of trimethylsilyl trifluoromethanesulfonate gave moderate yields of the N¹-(β-D-glucopyranosyluronate) barbiturate derivatives.The diastereomers of the phenobarbital derivatives were resolved by use of C₁₈ reversed-phase HPLC.The homologous N³-methyl barbiturate N¹-glucuronates were prepared by reaction of the barbital and phenobarbital N¹-glucuronate derivatives with diazomethane.The absolute configuration of the phenobarbital N¹-β-D-glucopyranuronate epimers was determined by oxidative removal of the glycon from the mephobarbital N¹-β-D-glucopyranuronate epimers to give the optical isomers of mephobarbital.The spectroscopic data for this series of compounds will facilitate the characterization of N-glycosylated imide xenobiotics that may be detected as mammalian metabolites in biodisposition studies. Keywords: D-glucopyranosyluronate derivatives; Glucuronides; Barbiturates; Synthesis