Total Synthesis and Anti-inflammatory Activity of Asperjinone and Asperimide C.

Total syntheses of two γ-butenolide natural products, asperjinone ( 1 ) and asperimide C ( 2 ) in both racemic and chiral forms have been accomplished utilizing Basavaiah's one-pot Friedel-Crafts/maleic anhydride formation protocol as a key strategy. Our syntheses verified the revised structure of 1 proposed by Williams et al. and the structure and absolute configuration of 2 reported by the Li group. This work also discloses the unprecedented anti-inflammatory activity of 1 . Synthetic 1 exhibited significant anti-inflammatory activity in renal proximal tubular epithelial cells (RPTEC) by suppression of gene expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 under LPS-induced renal inflammation condition and was superior to ( S )- 1 , rac - 2 , 2 , and a positive drug control, indomethacin. Moreover, compound 1 inhibited downstream signaling of inflammation by significantly reducing iNOS and COX-2 gene expression and total NO production. The anti-inflammatory activity of asperjinone ( 1 ) renders it a potential and promising candidate for developing novel anti-inflammatory agents against inflammation worsening acute kidney injury.