102(P-40) Diol, Triol, and Tetrol Derivatives of myo-Inositol, their Selective Reactions and the Application to Efficient Total Synthesis
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Inositol phosphates and phosphoinositides are now well known physiologically important molecules mainly as second messengers for intracellular signal transduction. As part of our efforts to establish convenient and practical syntheses of them, here we report selective phosphorylation of 3,4-diol, 2,3,6-triol and 3,4,5,6-tetrol derivatives of myo-inositol, using the phosphite-pyridinium tribromide method developed by us, and discuss also practical resolution of 1,2-cyclohexylidene-myo-inositol. Distannylene derivative transformed in situ from ketal 1 smoothly reacted with chiral acetylmandeloyl chloride to give L-3,6-dimandelate (42%) and D-products consisting of 3-mono ester (20%) as well as 3,6-ester (10%), that could be easily separated to optically pure products. In a similar manner, phosphorylation of 1 with pyrophosphate in place of the acid chloride afforded 2 in excellent yield. Diol 3 was treated with glycerol phosphite in the presence of pyridinium tribromide and 2,6-lutidine, resulting in the smooth and selective formation of 3-phosphate 4 in 88%. The product was unexpectedly deprotected at once under hydrogenolysis conditions using commercial AcOEt without purification as a solvent, giving PI(4,5)P2 with palmitoyls. Both enantiomers resolved were converted to triols 5 and 7, respectively. These triols were subjected to the same phosphorylation procedure as above, to afford exclusively 3-O-phosphorylation products 6 and 8, which were then deprotected in two-step procedure to give the same product, PI(3,5)P2. It should be noted that a pyridine-CH_2Cl_<2> (1:1) mixed solvent system was needed for the phosphorylation to take place. The role of pyridine is presumably to dissociate the aggregation state of the triols because they extraordinarily associate each other, as indicated by nmr analysis.
