A Unifying Concept for the Prebiotic Formation of RNA Pyrimidine Nucleosides

The question of how nucleosides might have formed as essential precursor molecules on the early Earth is one of the many challenges associated with the origin of life. In this context, the prebiotic synthesis of pyrimidine nucleosides is controversially discussed. For the pyrimidines, two at first glance contradictory prebiotically plausible reaction pathways have been proposed, based on either oxazole or isoxazole chemistry. This study shows that these two reaction sequences can be merged under prebiotically reasonable conditions, suggesting that both pathways could have co-existed and possibly interacted. The key precursor 3-aminoisoxazole was found to react with the key intermediate of the oxazole route (ribo-2-(methylthio)oxazoline), to form a ribo-isoxazole-oxazoline hybrid structure, which collapses upon reductive N−O bond cleavage to give the nucleoside cytidine. The data suggest that different, interacting prebiotically plausible chemical pathways may have created the key molecules of life on the early Earth.