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

Abstract

The D-3-phosphorylated myo-inositol phospholipids PtdIns(3)P, PtdIns(3,4)P2, PtdIns(3,4,5)P3 and PtdIns(3,5)P2 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 protein kinases (PKB and PDK-1) in which they played an important activation role.