Synthesis and iron binding studies of myo-inositol 1,2,3-trisphosphate and (+/-)-myo-inositol 1,2-bisphosphate, and iron binding studies of all myo-inositol tetrakisphosphates

Carbohydr Res. 1996 Feb 28;282(1):81-99. doi: 10.1016/0008-6215(95)00361-4.

Abstract

The first syntheses of the natural products myo-inositol 1,2,3-trisphosphate and (+/-)-myo-inositol 1,2-bisphosphate are described. The protected key intermediates 4,5,6-tri-O-benzoyl-myo-inositol and (+/-)-3,4,5,6-tetra-O-benzyl-myo-inositol were phosphorylated with dibenzyl N,N-di-isopropylphosphoramidite in the presence of 1H-tetrazole and subsequent oxidation of the phosphite. The crystal structures of the synthetic intermediates (+/-)-1-O-(tert-butyldiphenylsilyl)-2,3,O-cyclohexylidene-myo-inos itol and (+/-)-4,5,6-tri-O-benzoyl-1-O-(tert-butyldiphenylsilyl)-2,3-O-cycl ohexylidene- myo-inositol are reported. myo-Inositol 1,2,3-trisphosphate, (+/-)-myo-inositol 1,2-bisphosphate, and all isomeric myo-inositol tetrakisphosphates were evaluated for their ability to alter HO. production in the iron-catalysed Haber-Weiss reaction. The results demonstrated that a 1,2,3-grouping of phosphates in myo-inositol was necessary for inhibition, also that (+/-)-myo-inositol 1,2-bisphosphate potentiated HO. production. myo-Inositol 1,2,3-trisphosphate resembled myo-inositol hexakisphosphate (phytic acid) in its ability to act as a siderophore by promoting iron-uptake into Pseudomonas aeruginosa.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Biological Transport
  • Crystallography, X-Ray
  • Hydroxyl Radical
  • Indicators and Reagents
  • Inositol Phosphates / chemical synthesis
  • Inositol Phosphates / chemistry*
  • Inositol Phosphates / metabolism
  • Inositol Phosphates / pharmacology
  • Iron* / metabolism
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Phytic Acid / metabolism
  • Pseudomonas aeruginosa / metabolism
  • Structure-Activity Relationship

Substances

  • Indicators and Reagents
  • Inositol Phosphates
  • inositol 3,4-bisphosphate
  • Hydroxyl Radical
  • inositol 1,2,3-trisphosphate
  • Phytic Acid
  • Iron