Uracil reacts specifically with bis(perfluoroalkanoyl)peroxides under radical conditions to give perfluoroalkyl derivatives at C-5. The latter compounds lose two fluorine atoms readily at pH 8-9 to form perfluoroalkyl ketones, which exist in equilibrium with tetrahedral adducts. Since the half-time for loss of fluorine is ca. 20 min at pH 8, these compounds are potential irreversible labels for pyrimidine recognition sites in vivo. Under these conditions, the perfluoroalkylpyrimidines are 3-5 times as reactive as trifluoromethylpyrimidines, whose strong antiviral effects have been thoroughly demonstrated. The same radical perfluoroalkylation can be achieved with uridines. Although the carbon-fluorine bond is significantly more stable in the nucleoside series, conversion to ketones can also be achieved with sulfhydryl or cyanide catalysis. These ketones are reducible to secondary alcohols with sodium borohydride. The inductive effects of multiple fluorine atoms renders the alcohols highly acidic and readily capable of forming strong internal hydrogen bonds to functions at C-4. We anticipate that such hydrogen bonding will interfere with the intermolecular hydrogen bonding needed for effective base pairing in polynucleotide strands. Thus, such compounds may block cell division and act as antiviral and anticancer agents. Furthermore, hydrogen bonding to this position has been found essential for the action of PRPP synthetase. Analogous perfluoroalkyl groups have been introduced into purines, primarily at C-8; these compounds provide an additional series of """"""""preaffinity"""""""" labels. Our earlier studies on the chemistry of perfluoroalkylimidazoles indicated that such a group at C-8 of a purine should undergo loss of fluorine at physiological pH and provide, in vivo, a very reactive functional group capable of bonding to a protein or nucleic acid nucleophile. Current efforts involve the attachment of dideoxyribose moieties to these purine analogues. All of these compounds also have the potential of acting as inhibitors of cytidine deaminase; biological evaluations are in progress.
