Membrane-permeant analogues of the putative second messenger myo-inositol 3,4,5,6-tetrakisphosphate

Stefan Roemer, Christoph Stadler, Marco T. Rudolf, Bernd Jastorff, Carsten Schultz

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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 languageEnglish (US)
Pages (from-to)1683-1694
Number of pages12
JournalJournal of the Chemical Society - Perkin Transactions 1
Issue number14
StatePublished - Jul 21 1996
Externally publishedYes

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Second Messenger Systems
Inositol
Derivatives
Membranes
Phosphates
Phosphites
Phosphorylation
Enantiomers
Butyrates
Cyclization
Alkylation
Chlorides
Hydrogen bonds
Esters
inositol-3,4,5,6-tetrakisphosphate
Proteins

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Membrane-permeant analogues of the putative second messenger myo-inositol 3,4,5,6-tetrakisphosphate. / Roemer, Stefan; Stadler, Christoph; Rudolf, Marco T.; Jastorff, Bernd; Schultz, Carsten.

In: Journal of the Chemical Society - Perkin Transactions 1, No. 14, 21.07.1996, p. 1683-1694.

Research output: Contribution to journalArticle

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