SYNTHESIS OF L-SCYLLO-INOSITOL 1,2,4-TRISPHOSPHATE, SCYLLO-INOSITOL 1,2,4,5-TETRAKISPHOSPHATE AND PHOSPHOROTHIOATE AND DL-2-DEOXY-2-FLUORO-MYO-INOSITOL 1,4,5-TRISPHOSPHATE - OPTICAL RESOLUTION OF 6-DI-O-BENZYL-4,5-O-ISOPROPYLIDENE-SCYLLO-INOSITOL

Routes for the synthesis of scyllo-inositol tris- and tetrakis-phospha tes and 2-deoxy-2-fluoro-myo-inositol 1,4,5-trisphosphate from myo-ino sitol have been devised, For DL-scyllo-inositol 1,2,4-trisphosphate, 6 -di-O-benzyl-4,5-O-isopropylidene-scyllo-inositol was prepared from th e triflate of -3,6-di-O-benzyl-4,5-O-isopropylidene-myo-inositol by in version at C-2. Removal of the isopropylidene group and phosphorylatio n gave the protected trisphosphate, Deblocking with sodium in liquid a mmonia afforded racemic scyllo-inositol 1,2,4-trisphosphate, 6-di-O-be nzyl-4,5-O-isopropylidene-scyllo-inositol was resolved into its enanti omers by means of the crystalline 2-O-camphanate ester. The structure of one diastereoisomer, -)camphanoyl]-4,5-O-isopropylidene-scyllo-inos itol was determined by single-crystal X-ray crystallography. 6-di-O-be nzyl-4,5-O-isopropylidene-scyllo-inositol was used to prepare 1L-(-)-s cyllo-inositol 1,2,4-trisphosphate in a fashion analogous to the racem ic modification. DL-1-O-Allyl-3,6-di-O-benzyl-scyllo-inositol was isom erised to the (Z)-prop-1-enyl derivative, The propenyl group was then removed to give the meso-1,4-di-O-benzyl-scyllo-inositol. Phosphitylat ion followed by oxidation or sulfoxidation gave the fully protected te trakis-phosphate or -phosphorothioate, respectively, After deblocking and purification, scyllo-inositol 1,2,4,5-tetrakisphosphate and scyllo -inositol 1,2,4,5-tetrakisphosphorothioate were obtained. 6-di-O-benzy l-4,5-O-isopropylidene-scyllo-inositol was isomerised to the 1-O-[(Z)- propl-enyl] derivative which was converted into the 2-O-triflate. Disp lacement of the triflate using tetrabutylammonium fluoride proceeded w ith inversion of configuration to give sopropylidene-1-O-([(Z)-prop-1- enyl]-myo-inositol. Removal of propenyl and isopropylidene groups affo rded DL-3,6-di-O-benzyl-2-deoxy-2-fluoro-myo-inositol, which was phosp hitylated and the product oxidised to give the fully protected 2-fluor o trisphosphate, Deprotection furnished DL-2-deoxy-2-fluoro-myo-inosit ol 1,4,5-trisphosphate, These compounds will be useful probes for inve stigation of the polyphosphoinositide pathway of cellular signalling.