Synthesis of fluorinated benzophenones for biological activity probing

The benzophenone (BP) structure, with its unique biaryl twist, has been shown to be an important bioactive functionality and prevalent motif in natural products. In this work, the synthesis and characterization of new fluorinated BP synthons are reported. These new BP fragments may provide additional specificity in protein-ligand binding, due to new interactions that could come from the fluorine substituents in protein pockets. One monofluorinated BP fragment was accessed in 13 steps with an overall yield of 11% employing key reactions such as lithium halogen exchange, intramolecular anionic Fries rearrangement, and chemoselective oxidations. The second, difluorinated BP fragment was brought to the pre-oxidation stage. Current results demonstrate that the intramolecular Fries rearrangement is feasible for accessing mono- and difluorinated scaffolds. These fluorinated BP fragments will in future be incorporated into the natural product (-)-balanol framework for probing the isozyme selective inhibition within the AGC superfamily of kinases.