Granatripodins A-B, limonoids featuring a Tricyclo[3.3.1.02,8]nonane motif: Absolute configuration and agonistic effects on human pregnane-X-receptor

Bioorg Chem. 2021 Jun:111:104888. doi: 10.1016/j.bioorg.2021.104888. Epub 2021 Apr 5.

Abstract

Two unprecedented limonoids incorporating a sterically encumbered cyclopropane ring, named granatripodins A (1) and B (2), featuring the presence of a tricyclo[3.3.1.02,8]nonane motif, were obtained from seeds of the Thai Xylocarpus granatum. The planar structures and absolute configurations of these limonoids were unambiguously established by NMR investigations, TDDFT-ECD and DFT-NMR calculations, and single-crystal X-ray diffraction analysis (Cu Kα). Most notably, granatripodin A (1) exhibited agonistic effects on human pregnane-X-receptor at the concentration of 100.0 nM. The biosynthetic origins of these limonoids via a radical cascade reaction are proposed. This study exemplifies a universal approach for the stereochemical assignment of polycyclic compounds with a cyclopropane-embedded cage scaffold.

Keywords: Absolute configuration; Cyclopropane ring; Human pregnane–X–receptor agonist; Limonoid; Mangrove; Single-crystal X-ray diffraction analysis; Structural elucidation; Xylocarpus granatum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Humans
  • Limonins / chemistry
  • Limonins / isolation & purification
  • Limonins / pharmacology*
  • Meliaceae / chemistry
  • Molecular Conformation
  • Pregnane X Receptor / agonists*
  • Seeds / chemistry
  • Structure-Activity Relationship

Substances

  • Limonins
  • Pregnane X Receptor