Hemirubin: An intramolecularly hydrogen-bonded analogue for one-half bilirubin

A model for one-half bilirubin, the neurotoxic yellow-orange pigment of jaundice, 9-[2-(2-carboxyethyl)benzyl]-2,3,7,8-tetramethyl 1,10-dihydrodipyrrin (1, hemirubin) was synthesized following SnCl4-catalyzed Friedel-Crafts acylation at C(9) of 2,3,7,8-1-oxo-1,10-dihydrodipyrrin (7) with methyl o-(chlorocarbonyl)hydrocinnamate. Unlike earlier bilirubin model compounds, hemirubin is predicted and found to engage in intramolecular hydrogen bonding. Like bilirubin, the propionic acid carboxyl group of hemirubin is linked to the opposing dipyrrinone by intramolecular hydrogen bonds, and thus, 1 shares in some of the solution properties of its parent bilirubin, e.g., an acid that is less polar than its methyl ester.