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

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 o rthoformate 8. Key transformations included the regioselective DIBAL- and t rimethylaluminium-mediated cleavages of myo-inositol orthoformate intermedi ates 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 properti es of the phospholipids were evaluated against various protein kinases (PKB and PDK-1) in which they played an important activation role.