Homochiral ligations of amino acids by N-phosphorylation in water

<h2>Summary</h2> Biological homochirality is the intrinsic signature of life on our planet, yet the origin of homochirality from a racemic world remains a long-standing mystery. Previously, <i>N</i>-phosphoryl amino acids (<i>N</i>-P-aa) have been studied as a chemical model for the co-evolutional formation of oligopeptides and nucleic acids under prebiotically plausible conditions. In this work, we discovered that the proteinogenic amino acids could be self-activated by <i>N</i>-phosphorylation to form homochiral peptides with diastereoisomeric excess (<i>de</i>; %) up to 97.5% through enantioselective ligations in racemic aqueous systems. Meanwhile, <i>N</i>-P-aa were determined as the phosphoryl group donors for the activation of other amino acids through the formation of cyclic penta-coordinated phosphorus intermediates. Furthermore, <i>N</i>-P-aa are very stable under the basic conditions, and the homochiral ligations are initiated under acidic conditions. Our results uncover the potential role of prebiotic phosphorylation in the origins of biological homochirality.