Synthesis of racemic 5-phosphonate analogues of myo-inositol 1,4,5-tris- and 1,3,4,5-tetrakis-phosphate.
(+/-)-2,3,6-Tri-O-benzyl-5-O-p-methoxybenzyl-myo-inositol and (+/-)-2,6-di-O-benzyl-5-O-p-methoxy-benzyl-myo-inositol, accessible readily from (+/-)-3,6-di-O-allyl-1,2-O-cyclohexylidene-myo-inositol, were phosphitylated with dibenzyl N,N-di-isopropylphosphoramidite, and the resulting phosphite triesters were oxidised with tert-butyl hydroperoxide to give the corresponding fully protected myo-inositol 1,4-bis- (12) and 1,3,4-tris-phosphate (13) derivatives. Cleavage of the p-methoxybenzyl group from 12 and 13, phosphonylation with bis[6-(trifluoromethyl)benzotriazol-1-yl] methylphosphonate or (difluoromethyl)phosphonic di(1,2,4-triazolide), followed by treatment in situ with benzyl alcohol, and then hydrogenolysis of the benzyl groups gave the 5-methylphosphonate and 5-[(difluoromethyl)phosphonate] analogues of myo-inositol 1,4,5-tris- and 1,3,4,5-tetrakis-phosphate. The 5-methylphosphonate analogue of myo-inositol 1,4,5-trisphosphate acted as a calcium antagonist in permeabilized human platelets.
Dreef
C E
CE
Department of Chemistry, Leiden University, Netherlands.
Jansze
J P
JP
Elie
C J
CJ
van der Marel
G A
GA
van Boom
J H
JH
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives*; D007295:Inositol Phosphates; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis*; D013237:Stereoisomerism
D007295:Inositol Phosphates; D063065:Organophosphonates; C081655:inositol-1,3,4,5-tetrakisphosphate; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium