SYNTHESIS OF 3,4,5,6-TETRAKISPHOSPHATES OF DL-1,2-DIDEOXY-1,2-DIFLUORO-MYO-INOSITOL AND DL-1,2-DIDEOXY-1,2-DIFLUORO-SCYLLO-INOSITOL AS ANALOGS OF DL-MYO-INOSITOL 3,4,5,6-TETRAKISPHOSPHATE

DL-1,2-Dideoxy-1,2-difluoro-myo-inositol was prepared from DL-3,4,5,6- tetra-O-benzyl-myo-inositol in five steps in an overall yield of 36%. The fluoro substituents were introduced with DAST in separate steps by displacement of hydroxy substituents with inversion of stereochemistr y. Difluorination could not be achieved in one step because of competi ng formation of a 1,4-anhydro derivative. DL-1,2-Dideoxy-1,2-difluoro- scyllo-inositol was prepared in 42% overall yield using similar chemis try, with the required inversion of one stereocentre being accomplishe d by displacement of a tosyl group with caesium propionate, Both diflu oroinositol analogues increased the levels of phytic acid (InsP(6)) in a skeletal muscle cell line. Each compound was tetraphosphorylated wi th dibenzyl N,N-diisopropylphosphoramidite in the presence of 1H-tetra zole, with subsequent oxidation of the phosphite with MCPBA. The P-OBn groups were removed by H-2/Pd-C, and the sodium salts of the tetrakis phosphates of the difluoroinositol analogues were obtained by cation e xchange.