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

Ian D. Spiers, Christopher J. Barker, Sung-Kee Chung, Young-Tae Chang, Sally Freeman, John M. Gardiner, Peter H. Hirst, Peter A. Lambert, Robert H. Michell, David R. Poyner, Carl H. Schwalbe, Anthony W. Smith, Kevin R. H. Solomons

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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.
Original languageEnglish
Pages (from-to)81-99
Number of pages19
JournalCarbohydrate Research
Volume282
Issue number1
DOIs
Publication statusPublished - 11 Oct 1996

Keywords

  • Binding
  • sites
  • biological transport crystallography
  • x-ray
  • hydroxyl
  • radical indicators
  • reagents
  • inositol
  • phosphates
  • iron models
  • molecular conformation
  • molecular structure
  • phytic acid
  • pseudomonas
  • aeruginosa
  • structure-activity relationship

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