Total Synthesis and Anti-inflammatory Activity of Asperjinone and Asperimide C,Journal of Natural Products

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Total Synthesis and Anti-inflammatory Activity of Asperjinone and Asperimide C
Journal of Natural Products ( IF 3.3 ) Pub Date : 2024-08-07 , DOI: 10.1021/acs.jnatprod.4c00557
Kittisak Thongpat ₁ , Natthawat Milehman ₁ , Worarat Rojanaverawong _{2,

3} , Pannita Holasut ₃ , Sunhapas Soodvilai ₄ , Chutima S Vaddhanaphuti ₃ , Kwanruthai Tadpetch ₁

Affiliation

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.

中文翻译：

Asperjinone 和 Asperimide C 的全合成及其抗炎活性

利用Basavaiah 的一锅Friedel–Crafts/马来酸酐形成方案作为关键策略，完成了两种γ-丁烯内酯天然产物——外消旋和手性形式的阿司哌酮 ( 1 ) 和阿司酰亚胺 C ( 2 ) 的全合成。我们的合成验证了 Williams 等人提出的1的修订结构。以及Li组报道的2的结构和绝对构型。这项工作还揭示了1前所未有的抗炎活性。 Synthetic 1在 LPS 诱导的肾脏炎症条件下通过抑制促炎细胞因子 TNF-α、IL-1β 和 IL-6 的基因表达，在肾近端肾小管上皮细胞 (RPTEC) 中表现出显着的抗炎活性，并且优于 ( S ) -1 、 rac - 2、2 ，以及阳性药物对照吲哚美辛。此外，化合物1通过显着降低 iNOS 和 COX-2 基因表达以及总 NO 产生来抑制炎症的下游信号传导。阿司哌酮 ( 1 ) 的抗炎活性使其成为开发新型抗炎剂以对抗炎症恶化的急性肾损伤的潜在候选药物。

更新日期：2024-08-07

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