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 electrophilic reagents as the source of selective fluorination. These include but are not limited to F-TEDA, NFSi and XeF2. Key classes of compounds to be studied include alkenes, aromatics, carbohydrates, N- heterocycles, nucleosides and steroids.
Specific aims i nclude the generation of new materials and/or the development of better routes to compounds of known activity. To facilitate these directed syntheses, efforts will be made to define the bounds of applicability of these reagents and to learn the effects of catalysts on the regioselectivity of the processes. In addition to simple fluorination of pi bonds, the co-addition of nucleophilic species such as alcohols, amines, water, nitriles, thiols and C-acids will be investigated leading to fluoroalkoxylation, etc. and thus to the generation of fluoroethers, fluoroalcohols, fluoroamines, etc. Routes to the fluorination of aromatics, including heterocycles, both direct and via organometallics, will be investigate. Ring fluorination often greatly enhances bioactivity. The methods used are those standard to synthetic and mechanistic organic chemistry. Chromatographic techniques (GC, HPLC, and TLC) will be used for the analysis, separation and isolation of compounds. Structural characterization will be achieved by spectroscopic techniques (FT-NMR, GC-MS, FT-IR, UV-VIS). New compounds will be offered for biological activity screening to be carried out by arrangement with specialist in the area of bioactivity assessment.
