Synthesis of N-beta-D-glucopyranosyluronate derivatives of barbital, phenobarbital, metharbital, and mephobarbital.
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.
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Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond 23298-0540, USA.
Soine
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Paibir
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D001462:Barbital / Q000031:analogs & derivatives / Q000737:chemistry; D001463:Barbiturates / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003978:Diazomethane / Q000737:chemistry; D005965:Glucuronates / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008618:Mephobarbital / Q000031:analogs & derivatives / Q000737:chemistry; D010634:Phenobarbital / Q000031:analogs & derivatives / Q000737:chemistry; D013237:Stereoisomerism
D001463:Barbiturates; D005965:Glucuronates; C084822:metharbital; D008618:Mephobarbital; D001462:Barbital; D003978:Diazomethane; D010634:Phenobarbital