Potentially Prebiotic Synthesis of Aminoacyl-RNA via a Bridging Phosphoramidate-Ester Intermediate

[Image: see text] Translation according to the genetic code is made possible by selectivity both in aminoacylation of tRNA and in anticodon/codon recognition. In extant biology, tRNAs are selectively aminoacylated by enzymes using high-energy intermediates, but how this might have been achieved prior to the advent of protein synthesis has been a largely unanswered question in prebiotic chemistry. We have now elucidated a novel, prebiotically plausible stereoselective aminoacyl-RNA synthesis, which starts from RNA-amino acid phosphoramidates and proceeds via phosphoramidate-ester intermediates that subsequently undergo conversion to aminoacyl-esters by mild acid hydrolysis. The chemistry avoids the intermediacy of high-energy mixed carboxy-phosphate anhydrides and is greatly favored under eutectic conditions, which also potentially allow for the requisite pH fluctuation through the variable solubility of CO(2) in solid/liquid water.