A facile synthesis of fluorophores based on 5-phenylethynyluracils

Compact, fluorescent uracil aglycones and derivatives suitable for incorporation into the oligonucleotide mimic peptide nucleic acid (PNA) have been prepared by Sonogashira/CastroStephens coupling to monosubstituted pherylacetylenes. Cyclic 6(phenyl)furo[2,3-d]pyrimidin-2(3H)-ones were accessed by the Ag+-catalyzed cyclization of the 5-alkynyluracil precursors. Although this reaction was sluggish, it gave quantitative chemical yields. Electron-rich alkynes, such as p-methoxyphenylethyne, cyclize much more rapidly than electron-deficient alkynes. Adjustment of the reaction conditions permitted the synthesis of p-nitrophenylfuranouracil in excellent yield.