Chemical resolution of 1,2-O-cyclohexylidene-3,4-O-(tetraisopropyldisiloxane-1,3-diyl)-myo-inositol and synthesis of phosphatidyl-D-myo-inositol 3,5-bisphosphate from both L- and D-enantiomers

Chemical resolution of a versatile starting material, 1,2-O-cyclohexylidene-3,4-O-(tetraisopropyldisiloxane-1,3-diyl)- myo-inositol, which is used to access naturally occurring inositol phosphates and phosphatidylinositol phosphates, is described. Starting from both D- and L-enantiomers of the material, the synthesis of phosphatidyl-D-myo-inositol 3,5-bisphosphate [PtdIns(3,5)P2] has been conveniently accomplished via convergent routes. One of the key reactions in the synthetic procedure was the regioselective phosphorylation of suitably protected 1,2,4-triol derivatives of inositol. Phosphorylation of the triol attempted in a 1:12 (v/v) pyridine/CH2Cl2 mixture did not proceed at all, whereas in an optimized solvent system, pyridine/CH2Cl2 (1.1:1, v/v), the reaction afforded 68% of the desired 1-O-phosphate as a single product. Further investigation by H-1 NMR spectroscopy indicated that the reactivity of the three OHs on 1,2,4-triol derivatives is governed by intermolecular hydrogen bonding, which may be disrupted by an increase in the proportion of pyridine in the reaction solvent. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).