Synthesis of 1D-3-deoxy-, 1D-2,3-dideoxy-, and 1D-2,3,6-trideoxy-myo-inositol 1,4,5-trisphosphate from quebrachitol, their binding affinities, and calcium release activity

Syntheses of three optically pure, deoxygenated myo-inositol 1,4,5-trisphosphate analogues from quebrachitol are reported together with their binding affinities and ⁴⁵Ca²⁺ release activity. The ligand-binding affinities of the analogues were determined using membrane preparations from bovine adrenal cortex. The ⁴⁵Ca²⁺ release activities were compared to that of Ins(1,4,5)P₃, using the calcium mobilizing receptor of saponin permeabilized SH-SY5Y human neuroblastoma cells. 1d-3-deoxy-Ins(1,4,5)P₃ (26) and 1d-2,3-dideoxy-Ins(1,4,5)P₃ (22) exhibited very potent ligand and agonist properties, while 1d-2,3,6-trideoxy-Ins(1,4,5)P₃ (19) was much less potent. These data provide solid evidence of the critical role which HO-6 of Ins(1,4,5)P₃ plays in its binding affinity and its Ca²⁺ mobilizing activity.