Synthesis of Photoactivatable 1,2-O-Diacyl-sn-glycerol Derivatives of 1-L-Phosphatidyl-D-myo-inositol 4,5-Bisphosphate (PtdInsP(2)) and 3,4,5-Trisphosphate (PtdInsP(3))

Photoactivatable analogues of 1-L-phosphatidyl-D-myo-inositol 4,5-bisphosphate (PtdIns(4,5)P(2) or PtdInsP(2)) and the corresponding 3,4,5-trisphosphate (PtdIns(3,4,5)P(3) or PtdInsP(3)) were prepared from the two chiral precursors, methyl alpha-D-glucopyranoside and 1,2-isopropylidene-sn-glycerol. Two key synthetic transformations included the Ferrier rearrangement reaction to construct the optically-pure inositol skeleton and the sequential acylation of the primary and secondary hydroxyl groups on the glycerol derivatives. The sn-1-O-(6-aminohexanoyl) PtdInsP(2) and PtdInsP(3) derivatives were further modified to contain benzophenone photophores in unlabeled and high specific activity tritium-labeled forms.