Inositols active, derivatives

Ins(l,4,5)P3 is subject to rapid degradation to compounds without any regulatory activity, due to the effects of phosphatases. In addition, there are many other inositol phosphate derivatives (see Berridge Irvine, 1989). Thus, further phosphorylation of Ins(l,4,5)P3 may take place. Of the more highly phosphorylated inositol compounds, Ins(l,4,5,6)P4 in particular is attributed a regulatory function. 

No optically active derivatives of epi-inositol have been prepared. All asymmetrically substituted compounds listed in this Table are racemic. 6 p-aminoben-zoyl-.c p-nitrobenzoyl-. d Derived from the corresponding 5,6-di-O-acylated 1,2 3,4-di-O-isopropylidene-epi-inositols. Change of numbering (but not shift of groups) takes place on removal of the isopropylidene groups. 

All optically active derivatives are called d or l, based on the configuration of carbon 6. The configuration of carbon 6 is found by viewing the Fischer-type projection (p. 9) with carbons 5 and 1 away from the viewer and C-5 at the top. When an optically inactive cyclitol has been made asymmetric by substitution, the d or l is put at the beginning of the name, e.g., D-l-O-methyl-mwco-inositol, but 3-0-methyl-D-inositol. When an inositol derivative contains less than six asymmetric carbon atoms, it is named as a derivative of the related inositol that has the maximum number of CIS OH groups. If this leads to more than one possibility, the parent inositol is chosen that has the lowest possible number for its substituents CIS to the OH on carbon 1. 

It is noteworthy that diglyceride residues can also be linked with CDP. The product is an active derivative capable of reacting with inositol to give an inositol phosphatide. Cardiolipin, a bisphosphatidylglycerol, also might arise by a transfer of phosphatide groups. 

More recently, the importance of a group of highly polar inositol lipids, present in neutrophils and many other cell types, has been recognised. Activation of neutrophils by fMet-Leu-Phe results in the transient accumulation of phosphatidylinositol 3-phosphate (Ptdlns 3-P), phosphatidylinositol 3,4-bisphosphate (Ptdlns 3,4-P2) and phosphatidylinositol 3,4,5-trisphosphate (Ptdlns 3,4,5-P3). Apparently, the enzyme phosphatidylinositol 3-hydroxy (3-OH) kinase plays a key role in the formation of these novel lipids. This enzyme can catalyse the formation of these lipids from phosphatidylinositol, phosphatidylinositol 4-phosphate (Ptdlns 4-P) and phosphatidylinositol 4,5 bisphosphate (Ptdlns 4,5-P2) in vitro (Fig. 6.10). Alternatively, it is possible that Ptdlns 3,4-P2 and Ptdlns 3-P are derived from the sequential dephosphorylation of Ptdlns 3,4,5-P3. 

Messenger substances with hydrophobic character such as diacyl glycerol or the phosphatidyl inositol derivatives are membrane localized. The hydrophobic messengers reach membrane-associated effector proteins by diffusing through the plasma membrane and there regulate their activity. 

Y. Watanabe, M. Milani, and S. Ozaki, Synthesis of optically active inositol derivatives starting from D-glucurono-6,3-lactone, Chem. Lett. 123 (1987). 

---