Anhydrodihydroartemisinin and its 10-trifluoromethyl analogue: access to novel d-ring-contracted artemisinin trifluoromethyl ketones

J Org Chem. 2002 Feb 22;67(4):1253-60. doi: 10.1021/jo016091f.

Abstract

The preparation of the 10-trifluoromethyl hydroartemisinin, followed by dehydration, afforded the trifluoromethyl analogue 2 of anhydrodihydroartemisinin 1. The reactivity of these two glycals of artemisinin were compared in epoxidation and halogenation reactions. Iodination of glycal 1 in water and the further rearrangement of the produced iodo hemiacetal provided the new D-ring-contracted aldehyde 8alpha, where the methyl at C-9 is beta. Epoxidation of 10-trifluoromethyl anhydrodihydroartemisinin 2 stereoselectively provided the beta-epoxy ether 11 in high yield. When treated with hexafluoro-2-propanol or trifluoroethanol, 11 readily underwent a rearrangement yielding to the D-ring-contracted trifluoromethyl ketone 9alpha with retention of configuration at C-9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry
  • Artemisinins*
  • Catalysis
  • Hydrolysis
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Molecular Structure
  • Sesquiterpenes / chemical synthesis*
  • Sesquiterpenes / chemistry*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 10-trifluoromethylanhydrodihydroartemisinin
  • Antimalarials
  • Artemisinins
  • Sesquiterpenes
  • anhydrodihydroartemisinin
  • artemisinin