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.
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.
Spiers
I D
ID
Department of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK.
Barker
C J
CJ
Chung
S K
SK
Chang
Y T
YT
Freeman
S
S
Gardiner
J M
JM
Hirst
P H
PH
Lambert
P A
PA
Michell
R H
RH
Poyner
D R
DR
Schwalbe
C H
CH
Smith
A W
AW
Solomons
K R
KR
D001665:Binding Sites; D001692:Biological Transport; D018360:Crystallography, X-Ray; D017665:Hydroxyl Radical; D007202:Indicators and Reagents; D007295:Inositol Phosphates / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010833:Phytic Acid / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D007295:Inositol Phosphates; C051854:inositol 3,4-bisphosphate; D017665:Hydroxyl Radical; C092449:inositol 1,2,3-trisphosphate; D010833:Phytic Acid; D007501:Iron