Synthesis of myo-Inositol-1,4,5-trisphosphate and myo-Inositol-1,4-bisphosphate

Abstract

Racemic myo-inositol-1,4,5-trisphosphate and myo-inositol-1,4-bisphosphate, which are respectively a second messenger mobilizing Ca2+ and its physiological metabolite in the intracellular signal transduction pathway, were synthesized from myo-inositol. Because of the conformational rigidity, isopropylidene ketals were used in the synthesis as suitable blocking groups of inositol. myo-Inositol-1,4-bisphosphate was synthesized through phosphorylation of the 1,4-diol(3) with diphenylphosphorochloridate and a subsequent deprotection. Regioselective deprotection of the trans-isopropylidene ketal over the cis-ketal was accomplished by a controlled acid hydrolysis. Partial hydrolysis of an orthoacetate was carried out in order to obtain the precursor which was regioselectively acetylated at the axially disposed 2-OH group over the equatorial 1-OH. Tetrabenzylpyrophosphate and N,N-diisopropyldibenzylphosphoramidite were used for effective phosphorylations of suitably functionalized precursors of myo-inositol 1,4,5-trisphosphate. Sequential deprotection afforded myo-inositol-1,4,5-trisphosphate without migration of phosphate groups.