Rapid Activation of Amino Acids with Cyanide and Hypochlorite.

Abstract

Cyanogen chloride (NCCl) produced from the reaction of -CN with HOCl has previously been shown to afford activation of ribonucleotides. We now report that NCCl reacts with primary aliphatic amino acids to rapidly produce N-carbamoyl dipeptides in excellent yields (89-98%). Studies with l-alanine suggest that racemization of the amino acids does not occur significantly during the reaction. Quantum chemical (DFT) calculations predict that the mechanism proceeds via activated 2-amino-5(4H)-oxazolone intermediates, which undergo amino acid nucleophilic attack. NCCl can also be generated in situ from glycine and HOCl, enabling the "sacrificial activation" of glycine to form N-carbamoyl diglycine. At 70 °C, selective peptide bond hydrolysis yields N-carbamoyl glycine, which is a known peptide precursor. The findings herein build upon prior work involving NCCl in prebiotic ribonucleotide synthesis and activation, highlighting its potential as a general chemical activator for the prebiotic condensation of life's molecular building blocks.