Total synthesis of fluorinated analogues of inositol and inositol 1,4,5-trisphosphate

Abstract

Syntheses of fluorinated analogues of inositol and inositol 1,4,5-trisphosphate are described. 1-Deoxy-1-fluoro-scyllo-inositol, 2-deoxy-2,2-difluoro-myo-inositol, DL-2-deoxy-2-fluoro-scyllo-inositol 1,4,5-trisphosphate and DL-2-deoxy-2,2-difluoro-myo-inositol, 1,4,5-trisphosphate have been prepared. Preparation of the (—)-camphanate ester of DL-3,6-di-O-benzyl-2-deoxy-2,2-difluoro-4,5-O-isopropylidene-myo-inositol facilitated the chromatographic separation of diastereoisomers. The absolute configuration of the diastereoisomeric camphanate of the protected D-myo-inositol derivative was determined by single-crystal X-ray crystallography. The separated diastereoisomers, after removal of camphanate and isopropylidene moieties, were used to synthesize both the D- and the L-enantiomer of 2-deoxy-2,2-difluoro-myo-inositol 1,4,5-trisphosphate.