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

dl-3,4,5,6-Tetra-O-benzyl-1-deoxy-1-fluoro-scyllo-inositol was resolved using (−)-(1S, 4R)-camphanyl chloride. The diastereoisomers formed were separated and the structure of d-3,4,5,6-tetra-O-benzyl-2-(1S,4R)-camphanyl-1-deoxy-1-fluoro-scyllo-inositol was solved by X-ray crystallography to an R-factor of 4.2%. A series of manipulations led to the preparation of d-1,2-dideoxy-1,2-difluoro-myo-inositol 3,4,5,6-tetrakisphosphate and its enantiomer. The d-1,2-difluoro enantiomer stereospecifically inhibited CaMK II-activated Cl− current, but with low potency; however, efficacy of this compound was greatly enhanced by myo-inositol 3,4,5,6-tetrakisphosphate itself.