Synthesis of phosphatidylinositols

These groups were designed for use in the synthesis of phosphatidylinositol phosphates, where it was desirable to be able to cleave a benzoate without cleaving a glyceryl ester. 

Figure 11.21 Outline of synthesis of phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine and phosphatidylcholine. Note in the synthesis of phosphatidylinositol, the free base, inositol, is used directly. Inositol is produced in the phosphatase reactions that hydrolyse and inactivate the messenger molecule, inositol trisphosphate (IP3). This pathway recycles inositol, so that it is unlikely to be limiting for the formation of phosphatidylinositol bisphosphate (PIP )- This is important since inhibition of recycling is used to treat bipolar disease (mania) (Chapter 12, Figure 12.9). Full details of the pathway are presented in Appendix 11.5. Inositol, along with choline, is classified as a possible vitamin (Table 15.3).

Ikeda M. (1993). Reduction of phosphoinositide hydrolysis by L-amino-3-phosphonopropionate may be caused by the inhibition of synthesis of phosphatidylinositols. Neurosci. Lett. 157 87-90. 

Synthesis of phosphatidylinositol follows a slightly different pathway from the other phosphoglycerides. Phosphatidate is activated by CTP-phos-phatidate cytidyl transferase to form CDP-diacylglycerol. Free inositol is then incorporated by CDP-diacylglycerol inositol transferase, with the release of CMP. Phosphatidylinositol usually constitutes less than 5% of total milk phospholipids (Bitman and Wood, 1990). 

Mesaeli N., Tappia P.S., Suzuki S., Dhalla N.S., Panagia V. Oxidants depress the synthesis of phosphatidylinositol 4,5-bisphosphate in heart sarcolemma. Arch. Biochem. Biophys. 382... 

E) decreases synthesis of phosphatidylinositol 3,4,5-trisphosphate in response to parathyroid hormone. 

The design and synthesis of phosphatidylinositol polyphosphates lipids (PIPn) headgroup scaffolds (69) from (68) that could be conveniently functionalized to obtain a number of derivatized analogues of use for different studies, have been presented by Best and co-workers (Scheme 13). ... 

Xu Y, Sculimbrene BR, Miller SJ (2006) Streamlined synthesis of phosphatidylinositol (PI), PI3P, PI3,5P2, and deoxygenated analogues as potential biological probes. J Org Chem 71 4919 928... 

The total synthesis of phosphatidylinositol PI, phosphatidylinositol-3-phosphate (PI3P), 3,5-phosphate(PI3,5P2) and a range of deoxygenated versions as potential biological probes have been reported. A key step is catalytic asymmetric... 

Rameh, LE, Tolias, KE, Duckworth, BC and Cantley, LC (1997) Anew pathway for synthesis of phosphatidylinositol-4,5-bisphosphate. Nature, 390, 192-196. 

The preparation of phosphatidyl inositol derivatives with a thiophospho linkage has been reported,together with a synthesis of phosphatidylinositol 3-phosphate by diisopropyl carbodiimide-promoted migration of the 4-phosphate. ... 

Larsen and co-workers have developed two approaches for the synthesis of phosphatidylinositol dimannoside (PIM2) analogue (418) that mimicked the suppressive activity of natural PIMs. This analogue, where the inositol core was replaced by glycerol, was tested for its ability to suppress cellular inflammation in a mouse model of allergic asthma and showed to be elfective in suppressing airway eosinophilia. These data indicated that the inositol core was not essential for this suppressive activity. 

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