A novel one-pot TiO2-catalyzed synthesis of nucleobases and acyclonucleosides from formamide is reported. Since formamide can be formed under prebiotic conditions, these reactions have implications for the origin of life. While a number of purine derivatives have been found as products of non-TiO2-catalyzed reactions, important compounds that would not otherwise occur (namely, thymine, 5-hydroxymethyluracil, and acyclonucleosides) are formed in acceptable yields by TiO2-catalyzed reactions. Moreover, TiO2 selectively affects the rates of degradation of nucleobases, as single units and when embedded in polynucleotides.