Efficient synthetic routes to fluorinated isosteres of inositol and their effects on cellular growth

Efficient synthetic routes to several fluorinated isosteres of inositol have been developed that are based upon the unexpected selectivity observed in the (diethylamido)sulfur trifluoride reaction of polyhydroxylated cyclohexane derivatives. The conversion of D-pinitol to 1D-1,5-dideoxy-1,5-difluoro-neo-inositol and to 1D-1-deoxy-1-fluoro-myo-inositol is reported along with a mechanistic rationale for their formation. Furthermore, the cell growth inhibitory properties of three fluorinated inositol analogues on NIH 3T3 (normal fibroblasts) and v-sis-transformed NIH 3T3 cells are described. These inositol isosteres hold promise as tools for furthering our understanding of the phosphatidylinositol cascade and may also offer a new strategy in the treatment of neoplastic diseases.