Abstract
The central and conserved role of peptides in extant biology suggests that they played an important role during the origins of life. Strecker amino acid synthesis appears to be prebiotic, but the high pKaH of ammonia (pKaH = 9.2) necessitates high pH reaction conditions to realise efficient synthesis, which places difficult environmental constraints on prebiotic amino acid synthesis. Here we demonstrate that diamidophosphate reacts efficiently with simple aldehydes and hydrogen cyanide in water at neutral pH to afford N-phosphoro-aminonitriles. N-Phosphoro-aminonitrile synthesis is highly selective for aldehydes; ketones give poor conversion. N-Phosphoro-aminonitriles react with hydrogen sulfide at neutral pH to furnish aminothioamides. The high yield (73%–Quant.) of N-phosphoro-aminonitriles at neutral pH, and their selective transformations, may provide new insights into prebiotic amino acid synthesis and activation.
Highlights
The central and conserved role of peptides in extant biology suggests that they played an important role during the origins of life
Intrigued by the biological relationship between amino acids and nucleotides that is manifest in the genetic code, and the prebiotic reactions of HCN2, we hypothesised that an iminebased reaction might link sugar/nucleotide phosphorylation with amino acid phosphorylation to yield a robust, neutral pH Strecker reaction in water
The phosphoro–Strecker reaction provides a selective strategy for prebiotic amino acid synthesis: it is selective towards aldehydes, with poor conversion for ketone substrates, which thereby avoids the synthesis of non-biological α,α-disubstituted amino acids and leaves prebiotic ketones available to undergo other reaction pathways[24,25]
Summary
The central and conserved role of peptides in extant biology suggests that they played an important role during the origins of life. We demonstrate that diamidophosphate reacts efficiently with simple aldehydes and hydrogen cyanide in water at neutral pH to afford N-phosphoro-aminonitriles. The high yield (73%–Quant.) of N-phosphoro-aminonitriles at neutral pH, and their selective transformations, may provide new insights into prebiotic amino acid synthesis and activation. The efficiency and simplicity of Strecker amino acid synthesis from aldehydes (1, R2 = H), hydrogen cyanide (HCN) and ammonia[1] suggest that the Strecker reaction is a likely prebiotic amino acid synthesis[2]. The (prebiotic) electrophilic activation and oligomerisation of amino acids have been achieved with mixed success[4,5,6,7], but in extant biology, peptide synthesis begins with phosphorylation of amino acid 3. The proposed mechanism for cTMP activation involves initial nucleophilic attack of the amine moiety of amino acid 3 at the electrophilic phosphorus atom of cTMP, followed by formation of a five-membered phosphoramide intermediate[15]
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