Fluoro artemisinins: difluoromethylene ketones

J Org Chem. 2001 Nov 16;66(23):7858-63. doi: 10.1021/jo0158579.

Abstract

The reactions of the ring-contracted aldehydes, derived from anhydrodihydroartemisinin, with gem-difluoroenoxysilanes in the presence of BF(3).Et(2)O afforded the corresponding difluoromethylene ketol adducts in good yields. Similar Lewis acid catalyzed reactions of dihydroartemisinin acetate with the difluoroenoxysilanes provided the 10-substituted difluoromethylene ketones in good to moderate yields. Interestingly enough, the course and the stereochemistry of these reactions are highly dependent on the nature of the Lewis acids used; the addition reaction was accompanied by epimerization at C-9, and the stereochemistry at C-10 depends on the difluoroenoxysilane used. The best results were obtained using SnCl(4) to give the 9alpha,10beta-stereoisomer in high stereoselectivity. When 0.4 equiv of SnCl(4) was used for the reaction with the alpha-(4-methoxyphenylenoxysilane)-beta,beta-difluoroenoxysilane, however, a rearrangement of the endoperoxide was observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry
  • Artemisinins*
  • Drugs, Chinese Herbal / chemical synthesis
  • Drugs, Chinese Herbal / chemistry*
  • Fluorenes / chemistry*
  • Hydrocarbons
  • Ketones / chemistry*
  • Methane / analogs & derivatives*
  • Methane / chemistry*
  • Plasmodium falciparum / drug effects
  • Sesquiterpenes / chemical synthesis
  • Sesquiterpenes / chemistry*

Substances

  • Antimalarials
  • Artemisinins
  • Drugs, Chinese Herbal
  • Fluorenes
  • Hydrocarbons
  • Ketones
  • Sesquiterpenes
  • carbene
  • fluorene
  • artemisinin
  • Methane