Synthesis of racemic 5-phosphonate analogues of myo-inositol 1,4,5-tris- and 1,3,4,5-tetrakis-phosphate

✍ Scribed by Cornelis E. Dreef; Jan-Pieter Jansze; Cornelius J.J. Elie; Gijs A. van der Marel; Jacques H. van Boom

• Publisher: Elsevier Science
• Year: 1992
• Tongue: English
• Weight: 932 KB
• Volume: 234
• Category: Article
• ISSN: 0008-6215
• DOI: 10.1016/0008-6215(92)85037-z

✦ Synopsis

(+/-)-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.