For future investigations of the binding properties of D-myo-inositol 3,4,5,6- and 1,4,5,6-tetrakis-phosphate [D-Ins(3,4,5,6)P4 and D-Ins(1,4,5,6)P4, respectively] to their putative target proteins, a set of analogues with modifications of the 1(3)- and/or 2-hydroxy group has been prepared. The reaction sequences started from D-3,4,5,6-tetra-O-benzyl-myo-inositol or its D-1,4,5,6-enantiomer, respectively and allowed the introduction of groups with degenerative hydrogen-bonding potential like methoxy or chloride, replacing the hydroxy groups. Additionally, the corresponding DL-scylto-inositol precursor 24 was prepared by a stereochemically optimized reduction of the 2-inosose derivative 23. Classical protection/deprotection chemistry and subsequent phosphorylation employing a common phosphite approach yielded the tetrakisphosphate analogues la-e, 3. These derivatives were converted to the uncharged, bioactivalable acetoxymethyl esters 2a-e, 4. To avoid cyclization of phosphates during acetoxymethyl alkylation and to increase lipophilicity of the potentially membrane-permeant InsP4 derivatives hydroxy groups of the monosubstituted tetrakisphosphates were covered by intracellularly hydrolysable butyrates.
|Original language||English (US)|
|Number of pages||12|
|Journal||Journal of the Chemical Society - Perkin Transactions 1|
|State||Published - Jul 21 1996|
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