Robust Synthesis of Prebiotic Precursors in Drying Reactions of Amino Acids and Keto Acids

Abstract One of the many intriguing mysteries surrounding origins‐of‐life research is understanding how biopolymers and metabolism co‐evolved from the very beginning through a process of chemical evolution. In biology, metabolism and polymerization of keto acids and amino acids are highly intertwined, yet the interplay between these two processes, utilizing these two simple building blocks under mild prebiotic conditions and in the absence of catalysts, has not been explored. Previously, dried reactions have been shown to promote the formation of protopolymers via condensation‐dehydration reactions. However, drying reactions of biological metabolites have not been explored, despite the fact that dehydration reactions are also crucial in current metabolism. Here, we uncover a robust reaction between keto acids and amino acids under mild drying conditions, yielding a diverse array of products. These reactions occur under a broad range of conditions and in some cases result in the formation of macromolecular assemblies. These findings expand the known inventory of prebiotically plausible compounds that can be considered in the context of prebiotic chemistry and exemplify how metabolism‐first and polymer‐first models can be reconciled.