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  2. Discovery from Hypericum elatoides and synthesis of hyperelanitriles as α-aminopropionitrile-containing polycyclic polyprenylated acylphloroglucinols

Discovery from Hypericum elatoides and synthesis of hyperelanitriles as α-aminopropionitrile-containing polycyclic polyprenylated acylphloroglucinols

  • Commun Chem. 2024 Jan 2;7(1):1. doi: 10.1038/s42004-023-01091-1.
Jin-Yan Xie 1 Pengfei Li 1 Xi-Tao Yan 2 Jin-Ming Gao 3
Affiliations

Affiliations

  • 1 Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, 712100, Yangling, People's Republic of China.
  • 2 Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, 712100, Yangling, People's Republic of China. xty@nwsuaf.edu.cn.
  • 3 Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, 712100, Yangling, People's Republic of China. jinminggao@nwsuaf.edu.cn.
Abstract

The search for lead compounds with anti-neuroinflammatory activity from structurally 'optimized' Natural Products is a crucial and promising strategy in the quest to discover safe and efficacious agents for treating neurodegenerative diseases. A phytochemical investigation on the aerial portions of Hypericum elatoides led to the isolation of five nitrogenous polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperelanitriles A-D (1-4) and hyperelamine A (5). Their structures were determined by spectroscopic analysis, ECD and NMR calculations, and X-ray crystallography. To the best of our knowledge, compounds 1-4 represent the first examples of acylphloroglucinols featuring an α-aminonitrile moiety, while 5 is a rare enamine-containing PPAP. Further, the synthesis of these naturally occurring PPAP-based nitriles or amines was accomplished. Compound 5 exhibited inhibitory activity against LPS-activated NO production in BV-2 cells, potentially through the suppression of TLR-4/NF-κB signaling. Here we show the isolation, structural elucidation, synthesis, and bioactive evaluation of compounds 1-5.

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