Amphiphilic dipyrrinones: methoxylated [6]-semirubins

Replacing the typical β-alkyl substituents of [6]-semirubin and [6]-oxosemirubin, two intramolecularly hydrogen-bonded bilirubin analogs, with methoxy groups produces amphiphilic dipyrrinones. Synthesized from the respective 9H-dipyrrinones prepared by base-catalyzed condensation of 3,4-dimethoxypyrrolin-2-one with the appropriate pyrrole α-aldehyde, the 2,3-dimethoxy and 2,3,7,8-tetramethoxy analogs of [6]-semirubin are yellow-colored dipyrrinones that form intramolecularly hydrogen-bonded monomers in CDCl3, as deduced from 1H NMR NH chemical shifts. They are monomeric in CHCl3, as determined by vapor pressure osmometry. In contrast, in the solid, X-ray crystallography reveals supramolecular ribbons of intermolecularly hydrogen-bonded (dipyrrinone to dipyrrinone and acid to acid) 2,3,7,8-tetramethoxy-[6]-semirubin. The latter is approximately 20 times more soluble in water than the parent [6]-semirubin with four β-methyl groups.

Graphical abstractSynthesized from the corresponding 9H-dipyrrinones, [6]-semirubins 1 and 2 were shown to be intramolecularly hydrogen-bonded in CDCl3 by 1H NMR and monomeric in CHCl3 by vapor pressure osmometry. Yet X-ray crystallography of 1 indicates intermolecular hydrogen-bonded dimers.Figure optionsDownload full-size imageDownload as PowerPoint slide