A New Procedure for the Preparation of Bilirubin IIIα from Bilirubin IXα

Abstract

A procedure for the preparation of bilirubin IIIα with an overall 15% yield from the natural, unsymmetric bilirubin IXα is described which does not require hplc separation at any stage. The process involves: 1) quantitative, acid-catalyzed addition of ethanethiol to the exo vinyl group of bilirubin IXα to give the bilirubin IXα thioether adduct 1; 2) acid-catalyzed constitutional isomerization (scrambling) of 1 to a statistical mixture containing ca. 25% of the bilirubin IIIα bis-thioether adduct 2; 3) 3-chloroperoxybenzoic acid (or, less efficiently, periodate) oxidation of 2 (in that statistical mixture) to the corresponding, more polar, bis-sulfoxide 4, followed by its simple chromatographic separation from the reaction mixture; and 4) thermal elimination in the bis-sulfoxide 4 to bilirubin IIIα.