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

Carbohydr Res. 1995 Apr 19;269(2):259-72. doi: 10.1016/0008-6215(94)00358-m.

Abstract

The synthesis and characterization of barbital, phenobarbital, metharbital, and mephobarbital glucuronides is reported. The condensation of per(trimethylsilyl)-barbital and -phenobarbital with methyl 1,2,3,4-tetra-O-acetyl-beta-D-glucopyranuronate in the presence of trimethylsilyl trifluoromethanesulfonate gave moderate yields of the N1-(beta-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-beta-D-glucopyranuronate epimers was determined by oxidative removal of the glycon from the mephobarbital N1-beta-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.

MeSH terms

  • Barbital / analogs & derivatives
  • Barbital / chemistry
  • Barbiturates / chemical synthesis*
  • Barbiturates / chemistry
  • Chromatography, High Pressure Liquid
  • Diazomethane / chemistry
  • Glucuronates / chemical synthesis*
  • Glucuronates / chemistry
  • Magnetic Resonance Spectroscopy
  • Mephobarbital / analogs & derivatives
  • Mephobarbital / chemistry
  • Phenobarbital / analogs & derivatives
  • Phenobarbital / chemistry
  • Stereoisomerism

Substances

  • Barbiturates
  • Glucuronates
  • metharbital
  • Mephobarbital
  • Barbital
  • Diazomethane
  • Phenobarbital