Stereochemistry and Conformational Analysis of Hemirubin

Intramolecularly hydrogen-bonded analogs of the natural bile pigment, bilirubin, are very scarce. Nuclear Overhauser effect NMR studies of the newest analog, a hemirubin (1), confirms intramolecular hydrogen bonding and a ridge-tile-shaped conformation. 1H NMR studies of 1 at sufficiently low temperatures detect conformational enantiomerization, for which an activation barrier of ΔG‡∼16 kcal/mol at 25°C in CDCl3 has been estimated. Evidence for the presence of dimeric association at low temperatures or high concentrations of 1 is found by the appearance of new sets of resonances, data from which may be used to calculate: ΔG°298 K +3.4 kcal/mol, ΔH° −5.6 kcal/mol and ΔS° −30.3 cal/deg/mol.