Total Synthesis and Detection of the Bilirubin Oxidation Product (<i>Z</i>)‑2-(3-Ethenyl-4-methyl-5-oxo-1,5-dihydro‑2<i>H</i>‑pyrrol-2-ylidene)ethanamide (<i>Z</i>‑BOX A)

Abstract

The selective total synthesis of the pure <i>Z</i>-isomer of BOX A (<b>8a</b>), a product of oxidative heme degradation with significant physiological impact, was achieved in four to six steps starting from 3-bromo-4-methylfuran-2,5-dione (<b>1</b>). <i>Z</i>-BOX A forms a strong hydrogen bridge framework in the crystalline state. LC-MS techniques allow identification and characterization of isomeric forms of BOX A