Electro-oxidation of hispanolone and anti-inflammatory properties of the obtained derivatives

The electrochemical oxidation ((+)Pt-Ni(-)/NH4Br/MeOH) of the natural product hispanolone (1a) produced, in high yield (> 95%), spiro-tetracyclic compounds 7a-7d as a result of the intramolecular addition of the C-9 hydroxyl group into the C-16 position with the simultaneous addition of a CH3O group at the C-15 position of the hispanolone furan moiety. After the electrochemical oxidation, an acid-catalyzed slow secondary reaction occurred producing the previously undescribed alpha-butenolide derivative, iso-Leopersin G (9). An anti-inflammatory study with the electro-synthesized compounds showed that la has higher anti-inflammatory properties with very low cytotoxicity (e.g., the inhibition of TPA-induced ear edema assay IC50 = 1.05 mu M/ear, positive control indomethacin IC50 = 0.27 mu M/ear).