The preparation of racemic and enantiomerically pure myo-inositol derivatives as intermediates for the synthesis of phosphatidylinositol 3-, 3,4-bis-, and 3,4,5-tris-phosphates and for the synthesis of analogues of 1D-myo-inositol 1,3,4,5-tetrakisphosphate

Details of the products obtained by the tin-mediated allylation and benzylation of 1,2-O-isopropylidene-myo-inositol, which were previously described in a preliminary communication, are provided here. Some of the products from these reactions, particularly 3,4,6-tri-O-allyl- and 3,5,6-tri-O-allyl-1,2-O-isopropylidene-myo-inositol, have been used to prepare intermediates for the synthesis of the title compounds. The syntheses of the following are described: 1L-2,4,5,6-tetra-O-benzyl-1-O-p-methoxybenzyl-myo-inositol (an intermediate for phosphatidylinositol 3-phosphate), 1L-2,4,5-tri-O-benzyl-myo-inositol 1,6-bis(dibenzyl phosphate) and IL-2,4,5-tri-O-benzyl-1,6-di-O-p-methoxybenzyl-myo-inositol (intermediates for phosphatidylinositol 3,4-bisphosphate), 1L-2,4-di-O-benzyl-myo-inositol 1,5,6-tris(dibenzyl phosphate) and(+/-)-2,4-di-O-benzyl-1,5,6-tri-O-p-methoxybenzyl-myo-inositol (intermediates for phosphatidylinositol 3,4,5-trisphosphate). Some of the intermediates used in the above preparations were also used for the synthesis of myo-inositol derivatives suitable for the preparation of analogues of 1D-myo-inositol 1,3,4,5-tetra-kisphosphate. Thus 1L-2,4-di-O-benzyl-5-O-p-methoxybenzyl-myo-inositol (for a 5-phosphorothioate analogue), crystalline 1L-2,5-di-O-beazyl-1-O-p-methoxybenzyl-myo-inositol 3,5,6-tris(dibenzyl phosphate), and crystalline 1D-2,6-di-O-benzyl-myo-inositol 1,4,5-tris(dibenzyl phosphate) (for a 3-phosphorothioate analogue) were prepared. The possibilities of using the latter compound in syntheses of tritium-labelled 1D-myo-inositol 1,4,5-trisphosphate and 1,3,4,5-tetrakisphosphate are discussed. (C) 1996 Elsevier Science Ltd.