Synthesis and Analysis of Glucuronic Acid-Conjugated Metabolites of 4-Bromo-2,5-Dimethoxyphenethylamine.

Two glucuronic acid-conjugated metabolites of the psychoactive phenethylamine 2C-B were chemically synthesized for the first time, and a method to analyze them in urine was developed. The β-D-glucuronide of 4-bromo-2,5-dimethoxyphenylethylalcohol was synthesized using a glucuronyl donor and a Lewis acid catalyst; the β-D-glucuronide of 4-bromo-2,5-dimethoxyphenylacetic acid was produced by condensation followed by catalytic hydrogenation. Direct liquid chromatography/mass spectrometry of diluted urine allowed qualitative and semiquantitative evaluation of these metabolites. The simple method is expected to aid studies of 2C-B's metabolic fate.

Study at a glance

Abstract

In the study reported here, two glucuronic acid-conjugated metabolites of 4-bromo-2,5-dimethoxyphenethylamine (2C-B)-a ring-substituted psychoactive phenethylamine-were chemically synthesized for the first time and a method for analyzing them in urine was developed. β-D-Glucuronide of 4-bromo-2,5-dimethoxyphenylethylalcohol was successfully synthesized using methyl 2,3,4-tri-Ο-acetyl-1-O-(trichloroacetimidoyl)-α-D-glucuronate as a glucuronyl donor and boron trifluoride diethylether complex as a Lewis acid catalyst. β-D-Glucuronide of 4-bromo-2,5-dimethoxyphenylacetic acid was synthesized by condensing 4-bromo-2,5-dimethoxyphenylacetic acid and benzyl D-glucuronate followed by benzyl group deprotection based on catalytic hydrogenation. Two glucuronic acid-conjugated metabolites of 2C-B in urine were qualitatively and semiquantitatively evaluated via direct liquid chromatography/mass spectrometry (LC/MS) analysis of a diluted urine sample. The simple method proposed is expected to be useful for studying the metabolic fate of 2C-B.