Synthesis of d-1,2-dideoxy-1,2-difluoro-myo-inositol 3,4,5,6-tetrakisphosphate and its enantiomer as analogues of myo-inositol 3,4,5,6-tetrakisphosphate

Effects of Substituting a OH Group by a F Atom ind-Glucose. Ab Initio and DFT Analysis

“…Fluorine-substituted analogues of naturally occurring and biologically active organic compounds have become the focus of increasing interest. − ,− They are thought to provide insight into the interactions with enzymatic binding sites. , Thus, it has already become a common practice in bioorganic chemistry to replace a hydroxyl group for a fluorine to generate a fluorinated enzyme substrate or inhibitor in a given enzymatic process. − The rationale for such a strategy stems from similarities between a F atom and a OH group, with particular reference to polarity as well as the close isosteric relationship between fluorine and oxygen. ,, Consequently, a F atom is considered to be a good substitute of a OH group because it introduces a small steric disturbance . Once introduced, the high carbon−fluorine bond energy 10 renders the substituent relatively resistant to metabolic transformation .…”

“…Once introduced, the high carbon−fluorine bond energy 10 renders the substituent relatively resistant to metabolic transformation . Therefore, fluorinated analogues are potentially useful in studies of metabolism 1,11 and some of them in clinical diagnostics. − Although several groups of compounds were studied, ,− carbohydrates seem to attract most of the attention. Among carbohydrates, there are a number of successful examples where substitution of a OH group by a F atom resulted in a compound which possessed biochemical and biological activity.…”

Synthesis and Biological Activity of d- and l-chiro-Inositol 2,3,4,5-Tetrakisphosphate: Design of a Novel and Potent Inhibitor of Ins(3,4,5,6)P4 1-Kinase/Ins(1,3,4)P3 5/6-Kinase

“…The biological data from evaluation of D-and L-chiroinositol 2,3,4,5-tetrakisphosphate (3 and ent-3) can be used to further develop this structure-activity analysis and improve our understanding of the catalytic site of the multifunctional kinase, which normally binds the equatorial hydroxyl group at C-1 of Ins(3,4,5,6)P 4 or C-6 of Ins(1,3,4)P 3 for phosphorylation. When a phosphate group is introduced at this position by the kinase [to give Ins(1,3,4,5,6)P 5 (15) and Ins(1,3,4,6)P 4 (16), respectively], the data show that the inhibitory activity is reduced significantly. However, without an equatorial 1-hydroxyl, but with an axial one at this position, D-chiro-Ins(2,3,4,5)P 4 (3) was relatively well recognized, with an affinity only about 5-fold less than that of the endogenous inhibitor Ins(1,3,4)P 3 .…”

“…Ins (3,4,5,6)P 4 and its analogues have been synthesized by several groups. [12][13][14][15][16][17] Our aim in the present work was to design a synthesis of an analogue of this molecule and its enantiomer using the naturally occur-ring chiral inositol derivatives pinitol and quebrachitol, respectively, to avoid the tedious resolution of intermediates and to guarantee the optical purity of synthetic analogues. A focus upon designing new ligands based on the structure of Ins (3,4,5,6)P 4 is of 2-fold advantage.…”