Synthesis and in vitro antimalarial activity of sulfone endoperoxides

Bioorg Med Chem Lett. 1998 Apr 21;8(8):903-8. doi: 10.1016/s0960-894x(98)00141-3.

Abstract

A series of 4,8-dimethyl-4-phenylsulfonylmethyl-2,3-dioxabicyclo[3.3.1]+ ++nonanes, carrying a variety of substituents at position-8 (4) were prepared by a short and efficient method from R-(+)-limonene. Key reactions include thiol oxygen cooxidation, and alkylation and acylation of a sterically hindered tertiary alcohol compatible with the endoperoxy functionality. Some of compounds 4, which are structurally related to yingzhaosu A (2), were found to exhibit in vitro antimalarial activity comparable to that of artemisinin (1) and superior to that of arteflene (3).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Chloroquine / pharmacology
  • Drugs, Chinese Herbal
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Peroxides
  • Plasmodium falciparum / drug effects*
  • Sesquiterpenes / chemistry
  • Structure-Activity Relationship
  • Sulfones / chemical synthesis*
  • Sulfones / chemistry
  • Sulfones / pharmacology

Substances

  • Antimalarials
  • Drugs, Chinese Herbal
  • Peroxides
  • Sesquiterpenes
  • Sulfones
  • Chloroquine