Inositol 1,3,4,5-tetraphosphate

Fig. 9-214. Gradient elution of inositol phosphate isomers. — Separator column lonPac ASH (2-mm) eluant NaOH gradient linear, 5 mmol/L to 10 mmol/L in 2 min, then to 90 mmol/L in 10 min flow rate 0.5 mL/ min detection suppressed conductivity peaks (1) and (2) unknown, (3) chloride, (4) inositol-2-phosphate, (5) inositol-1-phosphate, (6) unknown, (7) carbonate, (8) sulfate, (9) unknown, (10) inositol-1,4-diphosphate, (11) orthophosphate, (12) inositol-4,5-diphosphate, (13) inositol-1,5,6-triphosphate, (14) inositol-1,2,5,6-tetraphosphate, (15) inositol-1,4,5-triphosphate, and (16) inositol-1,3,4,5-tetraphosphate.

The preparation of inositol and structurally related phosphates continues to be actively explored. Examples include the first total synthesis of the inositol tetraphosphate enantiomeric pair, Ins(l,2,3,4)P4 (27) and Ins(l,2,3,6)P4 (28). Compounds (27) and (28) were dephosphorylated by a number of different enzymes and thus provide routes to specific inositol triphosphates. A number of myo-inositol 1,4,5-triphosphates, e.g. (29)-(32), modified at the 6-position have been prepared. All such derivatives investigated showed poor affinity for Ins(l,4,5)P3 receptors. A new and comparatively convenient synthesis of I-d-6-0-(2-amino-2-deoxy-a-D-glycopyranosyl)-chiro-inositol 1-phosphate (33) and the corresponding 1,2-cyclic phosphate (34) has been reported. The first examples of poly(ethylene glycol)-linked dimers (35) of D-myo-inositol 1,4,5-triphosphate have been prepared as probes for multi-subunit binding proteins for... 

A number of tetraphosphate analogues, e.g. 24, have been prepared with a view to increasing cell membrane permeation properties. Routes to 3,4,5,6-tetrakis-phosphates, e.g. 25, of DL-l,2-dideoxy-l,2-difluoro-mjo-inositol and dl-1,2-dideoxy-1,2-difluoro-5cj//o-inositol have been reported.The fluoro substituents were introduced using DAST to displace hydroxy groups. However, the difluorina-tion could not be achieved in one step due to competing formation of a 1,4-anhydro derivative. The synthesis, from wjo-inositol monobenzoate derivatives, of all four... 

In the second synthesis, D and L-myo-inositol-2,4-dibenzyl ethers were both phosphicylated with (BnO)2PNPr 2 t6trazole subsequent oxidation with MCPBA and hydrogenolysis afforded the desired tetraphosphate (61). ... 

Inositol L-form 1,2,3,5-Tetra-O-angeloyl, 1-28 -Inositol L-form 1,2,4,5-Tetra-O-angeloyl, 1-28 -Inositol l,2 3,4-Di-0-cyclohexylidene, 5-benzoyl, 1-30 wyo-Inositol 1,4-Diphosphate, 1-32 wyo-Inositol 1-0-p-D-Glucopyranoside, nona-Me, 1-32 wyo-Inositol hexakis(phosphate), 1-32 wyo-Inositol monoorthoformate, 1-32 wyo-Inositol 1,2,3,4,5-Pentaphosphate, 1-32 wyo-Inositol 1,2,3,4,6-Pentaphosphate, 1-32 myo-Inositol 1,2,3,5,6-Pentaphosphate, 1-32 myo-Inositol 1,2,4,5,6-Pentaphosphate, 1-32 myo-Inositol 1,3,4,5,6-Pentaphosphate, 1-32 myo-Inositol 2,3,4,5,6-Pentaphosphate, 1-32 myo-Inositol 1-Phosphate, ( ), 1-32 myo-Inositol 4-Phosphate, ( ), 1-32 myo-Inositol 1-Phosphate, 1-32 myo-Inositol 2-Phosphate, 1-32 myo-Inositol 3-Phosphate, 1-32 myo-Inositol 4-Phosphate, 1-32 myo-Inositol 5-Phosphate, 1-32 myo-Inositol 6-Phosphate, 1-32 myo-Inositol 3,4,5,6-Tetra-Ac, 1-32 myo-Inositol 2,3,5,6-Tetrabenzyl, 1-32 myo-Inositol 1,3,4,5-Tetraphosphate, 1-32 myo-Inositol 1,3,5,6-Tetraphosphate, 1-32 myo-Inositol 1,4,5,6-Tetraphosphate, 1-32 myo-Inositol 3,4,5,6-Tetraphosphate, 1-32 myo-Inositol 2,4,6-TVibenzyl, 1,3,5-0-methylidyne, 1-32 myo-Inositol 2,3,5-Tribenzyl, 1-32 myo-Inositol 1,2,3-Triphosphate, 1-32 myo-Inositol 1,3,4-Triphosphate, 1-32 myo-Inositol 1,4,5-Triphosphate, 1-32 myo-Inositol 1,4,6-Triphosphate, 1-32 myo-Inositol 2,4,5-Triphosphate, 1-32 myo -Inositol-1,2,6-triphosphate, 1-32 fl//o-Inositol, 1-27 i -Inositol, 1-28 /-Inositol, 1-28 cw-Inositol, 1-29 ep/-Inositol, 1-30 mwco-Inositol, 1-31... 

Also reported is a full account of earlier work (Vol. 23, p. 186, ref. 66) on the chemo-en matic nthesis of D-myo-inositol 1,3,4-triphosphate and of D-myo-inositol 13.4,5-tetraphosphate. ... 

The preparation of 5-methylphosphonate and 5-(difluoromethyl)phosphonate analoguesof myoinositol 1,4,5-triphosphate and 1,3,4,5-tetraphosphate has been disclosed. Other phosphonate derivatives to have been synthesized include D,L-myo-inositol 1,4,5-trimethylphosphonate, 43-bis and 5-mono methyl phosphonates. ... 

Inositol Phosphates. - ID and IL-Myo-inositol 1,3,4,5-tetraphosphate have been prepared by a procedure similar to that used for the racemate reported last year (see Vol. 21, p. 183) the enantiomers of the starting 2,4-di-O-benzyl-myo-inositol were obtained following resolution of the diastereoisomeric carbamates (52) or enantio-... 

The synthesis of myo-inositol derivative (83) by esterification of racemic 2,3,4,5,6-pentabenzyl myo-inositol as a potential inhibitor of PLC has been reported." The synthesis of a phosphodiester derivative of D,L-myo-inositol 1,3,4,5-tetraphosphate has been described (Scheme 14)." The ester was subsequently linked via the amine to an affinity resin and a photoaffinity label in order to probe the IP4 receptor. 

Both inositol triphosphate and diacylglycerol can be metabolized by two separate pathways. Either diacylglycerol can be phosphorylated to yield phosphatidate, which then can go on to complete the cycle back to phosphatidylinositol or a lipase will cleave the fatty acid at the sn-2 position (often arachidonate). If arachidonic acid is released then it can initiate the arachidonate cascade (section 3.4.2 and 3.4.5). Likewise inositol 1,4,5-triphosphate can either be phosphorylated to give a tetraphosphate (which may itself produce cellular effects) or it can be hydrolysed via intermediates to yield inositol and again complete the cycle. 

---