Total Syntheses and Anti-Inflammatory Evaluation of Pd-Ib and Its Natural Stereoisomers

We reported the first enantioselective total synthesis of four naturally occurring angular dihydropyranocoumarins (<b>1</b>-<b>4</b>), each obtained in high enantiomeric excess (94-98% ee). The synthetic route featured Jacobsen epoxidation followed by anhydride-mediated angeloylation as key transformations. The anti-inflammatory properties of compounds <b>1</b>-<b>4</b> were evaluated using a panel of in vitro assays. Notably, compound <b>4</b> exhibited significant anti-inflammatory activity by reducing the secretion of proinflammatory cytokines. Results from Western blotting, in conjunction with molecular dynamics analysis, indicated that inhibition of the NF-κB signaling pathway may partially explain the anti-inflammatory activity of compound <b>4</b>.