General synthesis of 3-phosphorylated myo-inositol phospholipids and derivatives

摘要

The D-3-phosphorylated myo-inositol phospholipids PtdIns(3)P, PtdIns(3, 4)P_2, PtdIns(3, 4, 5)P_3 and PtdIns(3, 5)P_2 were synthesised from myo-inositol orthoformate 8. Key transformations included the regioselective DIBAL- and trimethylaluminium-mediated cleavages of myo-inositol orthoformate intermediates and a resolution-protection protocol using the camphor acetals 17. The final reductive debenzylation was effected with Pearlman's catalyst [Pd(OH)_2] in the presence of sodium hydrogen carbonate. The biological properties of the phospholipids were evaluated against various proteins kinases (PKB and PDK-1) in which they played an important activation role.