Synthesis of DFGH-Ring Derivatives of Physalins via One-Pot Construction of GH-Ring and Evaluation of Their NF-κB-Inhibitory Activity

Org Lett. 2020 Nov 20;22(22):8877-8881. doi: 10.1021/acs.orglett.0c03255. Epub 2020 Oct 30.

Abstract

We designed and synthesized a series of derivatives containing the right-side DFGH-ring structure of physalin-type natural products, decorated with a hydrophobic substituent. The synthetic scheme utilizes a highly efficient, one-pot protocol for simultaneous construction of the GH-ring system, promoted by HF/pyridine. Among the compounds synthesized, 5d inhibited TNF-α-stimulated NF-κB activation with similar potency to physalin B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Molecular Structure
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / chemistry
  • Secosteroids / chemical synthesis*
  • Secosteroids / chemistry
  • Signal Transduction
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / chemistry*

Substances

  • NF-kappa B
  • Secosteroids
  • Tumor Necrosis Factor-alpha
  • physalin B