Synthesis of the proposed structure of damaurone D and evaluation of its anti-inflammatory activity

Abstract

Concise and efficient synthesis of the proposed structure of damaurone D is accomplished in five steps without protection-deprotection operations. The key feature of our synthesis includes a versatile aldol reaction of the benzofuranone, provided by selective α-halogenation and intramolecular O-alkylation. However, the H- and C-NMR spectral data of the synthesized damaurone D did not agree with previous reports. The structure of the synthesized damaurone D was confirmed using combined two dimensional (2D)-NMR analysis, including heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond connectivity (HMBC), and nuclear Overhauser effect spectroscopy (NOESY). The synthesized damaurone D was found to exhibit potent anti-inflammatory activity in murine macrophage RAW264.7 cells, which was demonstrated by the findings that damaurone D treatment in cells resulted in the inhibition of lipopolysaccharide (LPS)- stimulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and nitrite production.