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.