Synthesis And Anti-Inflammatory Evaluation Of (R)-, (S)-, And (+/-)-Sanjuanolide Isolated From Dalea Frutescens

The known chalcone (+/-)-sanjuanolide (1) can be isolated from Dalea frutescens. This study presents a convergent strategy for the first total synthesis of (R)-, (S)-, and (+/-)-sanjuanolide (1). The key step for synthesizing (R)- and (S)-1 was a Corey Bakshi Shibata enantioselective carbonyl reduction to construct the C-2 '' configuration. (R)-1 efficiently inhibited the lipopolysaccharides (LPS)-induced expression of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), while (S)-1 produced no significant anti-inflammatory effect. (R)-1 also effectively inhibited the mRNA expression of several inflammatory cytokines after the LPS challenge in vitro. The synthesis and biological properties of these compounds have confirmed (R)-sanjuanolide and (+/-)-sanjuanolide as promising new leads for developing anti-inflammatory agents.