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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
Author(s) -
Han Fushe,
Hayashi Minoru,
Watanabe Yutaka
Publication year - 2004
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200300517
Subject(s) - chemistry , pyridine , inositol , regioselectivity , triol , solvent , nuclear magnetic resonance spectroscopy , reactivity (psychology) , stereochemistry , chemical synthesis , organic chemistry , medicinal chemistry , diol , in vitro , biochemistry , catalysis , medicine , receptor , alternative medicine , pathology
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/CH 2 Cl 2 mixture did not proceed at all, whereas in an optimized solvent system, pyridine/CH 2 Cl 2 (1.1:1, v/v), the reaction afforded 68% of the desired 1‐ O ‐phosphate as a single product. Further investigation by 1 H 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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)