Semisynthesis of epoxy-pimarane diterpenoids from kirenol and their FXa inhibition activities

Bioorg Med Chem. 2019 Apr 1;27(7):1320-1326. doi: 10.1016/j.bmc.2019.02.032. Epub 2019 Feb 16.

Abstract

Kirenol is one of the biologically active diterpenoids from Siegesbeckia pubescens. In terms of the high content and typical structure, many ent-diterpenoids separated from S. pubescens were presumed to be biologically related to kirenol. Among them, epoxy-pimarane diterpenoids are belonging to a special family of naturally occurring compounds that attracted our attentions on their putative biosynthesis pathway and biological activities. Here, we designed and synthesized two known 14,16-epoxy-pimarane diterpenoids (2 and 3) and five 8,15-epoxy-pimarane diterpenoids (4-8) from kirenol. Their absolute structures were determined by 1D and 2D NMR data and the absolute configurations of 4 were confirmed by X-ray crystallographic data. Their inhibition effects on factor Xa (FXa) were evaluated to assess the potentiality of epoxy-pimarane diterpenoids as FXa inhibitor agents.

Keywords: Epoxy-pimarane diterpenoids; Factor Xa; Kirenol; Siegesbeckia; Siegesbeckia pubescens; X-ray crystallographic data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / chemical synthesis
  • Abietanes / chemistry
  • Abietanes / pharmacology*
  • Crystallography, X-Ray
  • Diterpenes / chemistry*
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Epoxy Compounds / chemical synthesis
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / pharmacology*
  • Factor Xa / metabolism*
  • Factor Xa Inhibitors / chemical synthesis*
  • Factor Xa Inhibitors / chemistry
  • Factor Xa Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Abietanes
  • Diterpenes
  • Epoxy Compounds
  • Factor Xa Inhibitors
  • kirenol
  • pimarane
  • Factor Xa