Synthesis of biliverdin and bilirubin 1-O-acyl-beta-D-glucopyranuronic acids.
Biliverdin and bilirubin mono- and di-beta-glucuronides were prepared by nucleophilic substitution of the 1-O-mesyl derivative of alpha-ethoxyethyl-protected glucuronic acid (compound II) with the tetrabutylammonium salts of biliverdin and bilirubin. Removal of the acetal-protecting groups by mild acid treatment yielded biliverdin glucuronides, which were reduced to bilirubin glucuronides. Depending on reaction conditions the pure beta-anomers or mixtures highly enriched in the beta-anomers were obtained. The biliverdin and bilirubin glucuronides were identical with pigments derived from bile. They were characterized as the IX alpha isomers and the beta-anomers by alkaline hydrolysis, n.m.r. spectroscopy, hydrolysis with beta-glucuronidase and conversion into dipyrrolic azopigments. Model reactions of the 1-O-mesylate (II) with other nucleophiles also were performed, i.e. the acetate anion and various alcohols.
D001663:Bilirubin / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D001664:Biliverdine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D002855:Chromatography, Thin Layer; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010084:Oxidation-Reduction
D007202:Indicators and Reagents; C041840:biliverdin diglucuronide; C016266:bilirubin glucuronate; D001664:Biliverdine; D001663:Bilirubin