Semisynthesis of ent-norstrobane diterpenoids as potential inhibitor for factor Xa

Bioorg Med Chem Lett. 2018 Dec 15;28(23-24):3813-3815. doi: 10.1016/j.bmcl.2018.05.036. Epub 2018 May 17.

Abstract

A semisynthesis of two ent-strobane diterpenoids strobols C (7) and D (14) was accomplished via a Wagnar-Meerwein rearrangement. Compounds 7, 14, and the intermediate products were evaluated for their inhibition on factor Xa (FXa). Among all the compounds screened for FXa inhibitory activity, three compounds 6, 7, and 9 showed significant inhibitory activities with IC50 values of 1067 ± 164, 81 ± 11, 1023 ± 89 nM, respectively. The inhibitory activity on FXa described in this study highlight the importance of structural modification based on natural products in the development of FXa inhibitors.

Keywords: Ent-strobane diterpenoids; Factor Xa; Semisynthesis; Wagnar-Meerwein rearrangement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products / chemical synthesis
  • Biological Products / chemistry
  • Biological Products / pharmacology
  • Blood Coagulation / drug effects
  • Chemistry Techniques, Synthetic
  • Diterpenes / chemical synthesis
  • Diterpenes / chemistry*
  • Diterpenes / pharmacology*
  • Drug Discovery
  • Factor Xa / metabolism
  • Factor Xa Inhibitors / chemical synthesis
  • Factor Xa Inhibitors / chemistry*
  • Factor Xa Inhibitors / pharmacology*
  • Humans
  • Structure-Activity Relationship

Substances

  • Biological Products
  • Diterpenes
  • Factor Xa Inhibitors
  • Factor Xa