166320-97-4Relevant academic research and scientific papers
A Conformationally Restricted Cyclic Phosphate Analogue of Inositol Trisphosphate: Synthesis and Physicochemical Properties
Riley, Andrew M.,Guedat, Philippe,Schlewer, Gilbert,Spiess, Bernard,Potter, Barry V. L.
, p. 295 - 305 (1998)
The design and total synthesis of DL-6-deoxy-6-(hydroxymethyl)-scyllo-inositol 1:7-cyclic 2,4-trisphosphate (4), a conformationally restricted cyclic phosphate analogue of the second messenger inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], is described. The protected inosose 2,4,6/3,5-pentahydroxy-3,5-bis-O-(p-methoxybenzyl)-2,4,6-O- methylidynecyclohexanone (7) was obtained from myoinositol orthoformate in two steps, and Wittig methylenation and then hydroboration-oxidation using 9-BBN-H/OH-/H2O2 gave the axial hydroxymethyl derivative 9. A series of protection/ deprotection steps provided the diol 13, which was converted into two cyclic phosphate esters 14a and 14b, epimeric at phosphorus, by reaction with (benzyloxy)bis(N,N-diisopropylamino)phosphine/ 1H-tetrazole followed by m-CPBA. Two other hydroxyl groups were then exposed and phosphorylated, and total deprotection gave racemic 4. NMR studies confirmed that in 4 the phosphate group equivalent to the 4-phosphate of Ins(1,4,5)P3 is held in the positive gauche orientation and that the inositol ring maintains a chair conformation from pH 2 to 12. Investigation of the acid-base properties of 4 using potentiometric and 31P NMR techniques showed that, over the physiological pH range, 4 behaves as a diprotic acid and that the ionization of the phosphate group equivalent to the 5-phosphate of Ins(1,4,5)P3 is enhanced. In biological assays, 4 appears to behave as a weak full agonist at the platelet Ins(1,4,5)P3 receptor, and the possible interpretation of this result is discussed.
6-Deoxy-6-hydroxymethyl scyllo-inositol 1,2,4-trisphosphate: A potent agonist at the inositol 1,4,5-trisphosphate receptor
Riley, Andrew M.,Murphy, Christine T.,Lindley, Catherine J.,Westwick, John,Potter, Barry V. L.
, p. 2197 - 2200 (1996)
The synthesis of racemic 6-deoxy-6-hydroxymethyl scyllo-inositol 1,2,4-trisphosphate is described. This compound is a highly potent agonist at the platelet D-myo-inositol 1,4,5-trisphosphate receptor, and it binds to the rat cerebellar receptor with an affinity equal to that of the natural ligand. These results suggest that the 5''-hydroxymethyl group of adenophostin A may contribute to its unusual potency.
