Novel 3',6'-anhydro and N12,N13-bridged glycosylated fluoroindolo[2,3-a]carbazoles as topoisomerase I inhibitors. Fluorine as a leaving group from sp3 carbon

Org Lett. 2005 Mar 31;7(7):1271-4. doi: 10.1021/ol050013n.

Abstract

[reaction: see text] Both 6'- and 4'-fluoro-glycosylated indolo[2,3-a]carbazoles are substrates for base-induced loss of fluorine as a leaving group from sp3 carbon. In the case of alpha-N-glycosylated substrate 3, loss of fluorine from the 6'-position leads to 3,6-anhydroglucose analogue 1. A novel N12,N13-bridged sugar analogue 2 results from loss of 4'-fluorine from beta-N-glycosylated analogue 4. Both analogues 1 and 2 display topo I inhibitory potencies similar to camptothecin.

MeSH terms

  • Animals
  • Carbazoles / chemical synthesis*
  • Carbazoles / pharmacology
  • Carbon / chemistry*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Fluorine / chemistry*
  • Glycosides / chemical synthesis*
  • Glycosides / pharmacology
  • Heterocyclic Compounds, Bridged-Ring / chemical synthesis*
  • Heterocyclic Compounds, Bridged-Ring / pharmacology
  • Hydrocarbons, Fluorinated / chemical synthesis*
  • Hydrocarbons, Fluorinated / chemistry
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Leukemia P388
  • Molecular Conformation
  • Molecular Structure
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors*

Substances

  • Carbazoles
  • Enzyme Inhibitors
  • Glycosides
  • Heterocyclic Compounds, Bridged-Ring
  • Hydrocarbons, Fluorinated
  • Indoles
  • Topoisomerase I Inhibitors
  • Fluorine
  • Carbon