Inositol polyphosphates, diphosphoinositol polyphosphates and phosphatidylinositol polyphosphate lipids: Structure, synthesis, and development of probes for studying biological activity

Synthesis of Highly Water-Soluble Adamantyl Phosphoinositide Derivatives

“…Ceric ammonium nitrate (CAN) oxidation successfully removed the PMB group to afford the 1,2-di-Oadamantanecarbonyl-sn-glycerol 4 in 79 % yield. Phosphitylation of the resulting alcohol with the bisphosphoramidite (BnO) P(N i Pr) 2 , [8] in the presence of 1H-tetrazole, provided the diadamantyl glycerol-side chain phosphoramidite 5 in 90 % yield.…”

“…The final step employed global hydrogenolytic cleavage under pressure in the presence of a palladium catalyst. [8] In the case of the PI(4,5)P 2 derivative, conditions using Pd black (20 equiv.) in a 6 : 1 tert-butanol/water mixture containing sodium bicarbonate gave the adamantane-PI(4,5)P 2 derivative 10 as the sodium salt in 62 % yield.…”

“…[4] The development of new probes for investigating phosphoinositide function is therefore of high importance from a biological and a pharmaceutical view point. [5][6][7] There are eight known naturally occurring PIPs, varying only in the phosphorylation status of the 3-, 4-, and 5-positions of the myo-inositol head group of the phospholipid (summarised in Fig. 1).…”

“…However, in plants, a range of carboxylic acids from palmitic acid (16 : 0) and stearic acid to linoleic acid (18 : 2) can be found at the sn-1 position with linoleic acid at the sn-2 position. [8,9] We have previously described the synthesis of all eight derivatives of the PIP family of compounds and analogues carrying an v-N-terminal substituent on the sn-1 chain for each compound. [10] This modification was used to immobilised these lipids onto affinity beads for proteomic studies and onto a Biacore TM chip for detailed evaluation of the affinity of different PIP-binding proteins for their cognate ligands.…”

“…[12] Enantiomerically pure compounds were obtained through diastereomeric resolution, using camphanic derivatives, in order to achieve separation of the diastereomers. [8] The synthetic derivatives of these molecules were used to form liposomes for characterisation purposes. [13,14] However, it is not always desirable to form liposomes or higher-order aggregates when studying such compounds.…”