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

A new de novo synthesis of the enantiomeric pair D-myo-inositol 1,2,4-trisp hosphate and D-myo-inositol 2,3,6-trisphosphate is described. Starting from enantiopure dibromocyclohexenediol, several C-2 Symmetrical building block s were synthesized which gave access to D-myo-inositol 1,2,4,5-tetrakisphos phate and D-Myo-inositol 1,2,3,6-tetrakisphosphate. Exploiting the high reg iospecificity of two partially purified phosphohydrolases from Dictyosteliu m, a 5-phosphatase and a phytase, the inositol tetrakisphosphates were conv erted enzymatically to the target compounds. Their potential to modulate th e activity of Ins(3,4,5,6)P-4 I-kinase was investigated and compared with t he effects Of D-myo-inositol 1,3,4-trisphosphate. (C) 2001 Elsevier Science Ltd. All rights reserved.