Synthesis of Photoactivatable 1,2-O-Diacyl-sn-glycerol Derivatives of 1-l-Phosphatidyl-d-myo-inositol 4,5-Bisphosphate (PtdInsP2) and 3,4,5-Trisphosphate (PtdInsP3)

Abstract

Photoactivatable analogues of 1-l-phosphatidyl-d-myo-inositol 4,5-bisphosphate (PtdIns(4,5)P₂ or PtdInsP₂) and the corresponding 3,4,5-trisphosphate (PtdIns(3,4,5)P₃ or PtdInsP₃) were prepared from the two chiral precursors, methyl α-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) PtdInsP₂ and PtdInsP₃ derivatives were further modified to contain benzophenone photophores in unlabeled and high specific activity tritium-labeled forms.