Synthesis and Anti-inflammatory Evaluation of ( R)-, ( S)-, and (±)-Sanjuanolide Isolated from Dalea frutescens.

Abstract

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-α) 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.