A NEW PROCEDURE FOR THE PREPARATION OF BILIRUBIN-III-ALPHA FROM BILIRUBIN-IX-ALPHA

A procedure for the preparation of bilirubin IIIalpha with an overall 15% yield from the natural, unsymmetric bilirubin IXalpha is described which does not require hplc separation at any stage. The process invo lves: 1) quantitative, acid-catalyzed addition of ethanethiol to the e xo vinyl group of bilirubin IXalpha to give the bilirubin IXalpha thio ether adduct 1; 2) acid-catalyzed constitutional isomerization (scramb ling) of 1 to a statistical mixture containing ca. 25% of the bilirubi n IIIalpha bis-thioether adduct 2; 3) 3-chloroperoxybenzoic acid (or, less efficiently, periodate) oxidation of 2 (in that statistical mixtu re) to the corresponding, more polar, bis-sulfoxide 4, followed by its simple chromatographic separation from the reaction mixture; and 4) t hermal elimination in the bis-sulfoxide 4 to bilirubin IIIalpha.