A Unifying Concept for the Prebiotic Formation of RNA Pyrimidine Nucleosides

Abstract

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 NÀ 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.

Equilibrium and Non‐equilibrium Reaction Schemes for Prebiotic Polymerization of Ribonucleotides

“…[7] There has been success in the laboratory in synthesizing nucleotides by these alternative routes, [8] and in putting nucleoside synthesis into a chemical context in which other biomolecules can also be synthesized. [9][10][11] Indeed, chemical scenarios appear to link well with geological/astrophysical scenarios in which synthesis of organic molecules is possible on the early Earth following a major meteorite impact which creates the required reducing conditions in the atmosphere. [12] Thus, we consider it likely that a supply of abiotically synthesized nucleosides was available on the early Earth.…”

“…Breaking of a bond occurs at rate b 1 and leads to the reformation of the cyclic phosphate on the first oligomer, i. e. the reaction is reversible [Eq. (11)].…”

“…However, there are other potential routes to synthesis of nucleosides that do not require the connection of a pre‐formed ribose with a pre‐formed nucleobase [7] . There has been success in the laboratory in synthesizing nucleotides by these alternative routes, [8] and in putting nucleoside synthesis into a chemical context in which other biomolecules can also be synthesized [9–11] . Indeed, chemical scenarios appear to link well with geological/astrophysical scenarios in which synthesis of organic molecules is possible on the early Earth following a major meteorite impact which creates the required reducing conditions in the atmosphere [12] .…”