ORGANOFLUORINE COMPOUNDS OF BIOLOGICAL INTEREST VIA SELECTIVE FLUORINATIONS

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This project will explore synthetic routes to the generation of biologically active C-fluorinated compounds via selective fluorinations. The incorporation of fluorine into an organic system often has a pronounced effect on the biological activity of the substrate. Primary focus will be on the use of xenon difluoride as the selective fluorination reagent, although other electrophilic reagents may also be used. Key classes of compounds to be studied include carbohydrates, N- heterocycles, nucleosides, and lipids. Specific aims include the generation of new materials in quantities sufficient for biological testing and/or the development of better routes to compounds of known activity. These routes could be used with F-18 reactants to generate compounds of value involving radioisotopes for applications such as positron emission tomography. To facilitate these directed syntheses, efforts will be made to better understand the mechanism of the selective fluorinations and in particular to learn the effects of catalysts on the regioselectivity of the process. In addition to simple fluorination of pi bonds, the co-addition of other species such as alcohols, amines, water and thiols will be investigated leading to fluoroalkoxylation, etc. Routes to aromatic fluorinations via organometallics will be investigated since fluorination of the aromatic ring often greatly enhances bioactivity and direct routes to accomplish this are limited. The methods used are those standard to synthetic and mechanistic organic chemistry. A variety of chromatographic techniques (GC, HPLC, and TLC) will be used for the analysis, separation and isolation of compounds. Structural characterization will be accomplished through several spectroscopic techniques (NMR, MS, FT-lR, UV). The biological testing of the resulting compounds will be carried out by arrangement with specialists in the area of medicinal chemistry.