Communications Chemistry (Jan 2024)

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

  • Jin-Yan Xie,
  • Pengfei Li,
  • Xi-Tao Yan,
  • Jin-Ming Gao

DOI
https://doi.org/10.1038/s42004-023-01091-1
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 9

Abstract

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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.