Antimalarial activity of novel 1,2,5,6-tetraoxacycloalkanes and 1,2,5-trioxacycloalkanes

J Med Chem. 2003 May 8;46(10):1957-61. doi: 10.1021/jm020387b.

Abstract

Photooxygenation of 2-phenylnorbornene 1 in the presence of 30% aqueous hydrogen peroxide afforded 1,2-bishydroperoxide 3, which could be cycloalkylated on treatment with silver oxide and a 1,omega-diiodoalkane to provide the tricyclic peroxides 12. Trimethylsilylation of 3 followed by TMSOTf-catalyzed cyclocondensation with carbonyl compounds led to the formation of the tricyclic peroxides 14 containing a 1,2,4,5-tetroxepane structure. Photooxygenation of 1 in the presence of either unsaturated hydroperoxides or unsaturated alcohols followed by bis(collidine)iodine hexafluorophosphate promoted cyclization gave the corresponding cyclic peroxides 15-17. Several of these cyclic peroxides showed substantial antimalarial activity particularly in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Crystallography, X-Ray
  • Mice
  • Peroxides / chemical synthesis*
  • Peroxides / chemistry
  • Peroxides / pharmacology
  • Plasmodium falciparum / drug effects
  • Tumor Cells, Cultured

Substances

  • Antimalarials
  • Bridged Bicyclo Compounds, Heterocyclic
  • Peroxides