Chemical Synthesis of all Naturally Occurring Phosphorylated Inositol Phospholipids

Studies of signal transduction pathways involving phosphoinositides constitute an important field of research in current cell physiology [1,2]. These compounds are now known to be involved in the transduction of the vast range of extracellular signals ranging from neurotransmission to vesicular trafficking [3]. Overall, of the eight major inositol phospholipids (PIPn) 1–8 (Figure 1) so far identified in cellular signaling pathways, only three, including phosphatidylinositol (1), phosphatidylinositol 4-phosphate (3) and 4,5- bisphosphate (7), are available in sufficient quantities by isolation from natural sources. Other phosphoinositides, while playing important roles in cell physiology, are formed either transiently, or are present in only very low concentrations, making their preparative isolation from natural sources impractical. Because of the above, the progress in unraveling the complex metabolic pathways involving inositol phospholipids has been reached largely after synthetic analogs of PIPn had become available [4–13].