Regiospecific phosphohydrolases from Dictyostelium as tools for the chemoenzymatic synthesis of the enantiomers -myo-inositol 1,2,4-trisphosphate and -myo-inositol 2,3,6-trisphosphate: non-physiological, potential analogues of biologically active -myo-

A new de novo synthesis of the enantiomeric pair -myo-inositol 1,2,4-trisphosphate and -myo-inositol 2,3,6-trisphosphate is described. Starting from enantiopure dibromocyclohexenediol, several C2 symmetrical building blocks were synthesized which gave access to -myo-inositol 1,2,4,5-tetrakisphosphate and -myo-inositol 1,2,3,6-tetrakisphosphate. Exploiting the high regiospecificity of two partially purified phosphohydrolases from Dictyostelium, a 5-phosphatase and a phytase, the inositol tetrakisphosphates were converted enzymatically to the target compounds. Their potential to modulate the activity of Ins(3,4,5,6)P4 1-kinase was investigated and compared with the effects of -myo-inositol 1,3,4-trisphosphate.