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)

The selective total synthesis of the pure Z-isomer of BOX A (8a), 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 (1). Z-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.