D-Glucose-Derived 1,2,4-Trioxepanes: Synthesis, Conformational Study, and Antimalarial Activity

Org Lett. 2015 Aug 21;17(16):4074-7. doi: 10.1021/acs.orglett.5b01996. Epub 2015 Aug 3.

Abstract

New enantiomerically pure 1,2,4-trioxepanes 10a,b/11a,b were synthesized from D-glucose. Their conformational behavior was studied by low-temperature NMR and substantiated by DFT calculations. On evaluation of in vitro antimalarial activity, the adamantyl derivative 11b showed IC50 values in the low micromolar range, particularly against the W2 chloroquine-resistant Plasmodium falciparum strain (IC50 = 0.15 ± 0.12 μM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / chemical synthesis*
  • Adamantane / chemistry
  • Adamantane / pharmacology*
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Chloroquine / pharmacology
  • Dose-Response Relationship, Drug
  • Glucose / chemistry*
  • Molecular Conformation
  • Molecular Structure
  • Oxepins / chemical synthesis*
  • Oxepins / chemistry
  • Oxepins / pharmacology
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / genetics
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Oxepins
  • Chloroquine
  • Glucose
  • Adamantane