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

✍ Scribed by Suzanne M. Neighbors; William H. Soine; Sheela G. Paibir

• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 754 KB
• Volume: 269
• Category: Article
• ISSN: 0008-6215
• DOI: 10.1016/0008-6215(94)00358-m

✦ Synopsis

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-/3-D-glucopyranuronate in the presence of trimethylsilyl trifluoromethanesulfonate gave moderate yields of the Nl-(fl-D-glucopyranosyluronate) barbiturate derivatives. The diastereomers of the phenobarbital derivatives were resolved by use of C18 reversed-phase HPLC. The homologous N3-methyl barbiturate Nl-glucuronates were prepared by reaction of the barbital and phenobarbital Nl-glucuronate derivatives with diazomethane. The absolute configuration of the phenobarbital N 1-/3-D-glucopyranuronate epimers was determined by oxidative removal of the glycon from the mephobarbital N1-/3-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.