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. 2023 May 17;145(19):10533-10541.
doi: 10.1021/jacs.2c13306. Epub 2023 May 5.

Prebiotic Synthesis of N- Formylaminonitriles and Derivatives in Formamide

Nicholas J Green  1   2 , David A Russell  1 , Sasha H Tanner  2 , John D Sutherland  1
Affiliations

Prebiotic Synthesis of N- Formylaminonitriles and Derivatives in Formamide

Nicholas J Green et al. J Am Chem Soc. .

Abstract

Amino acids and their derivatives were probably instrumental in the transition of prebiotic chemistry to early biology. Accordingly, amino acid formation under prebiotic conditions has been intensively investigated. Unsurprisingly, most of these studies have taken place with water as the solvent. Herein, we describe an investigation into the formation and subsequent reactions of aminonitriles and their formylated derivatives in formamide. We find that N-formylaminonitriles form readily from aldehydes and cyanide in formamide, even in the absence of added ammonia, suggesting a potentially prebiotic source of amino acid derivatives. Alkaline processing of N-formylaminonitriles proceeds with hydration at the nitrile group faster than deformylation, protecting aminonitrile derivatives from reversion of the Strecker condensation equilibrium during hydration/hydrolysis and furnishing mixtures of N-formylated and unformylated amino acid derivatives. Furthermore, the facile synthesis of N-formyldehydroalanine nitrile is observed in formamide from glycolaldehyde and cyanide without intervention. Dehydroalanine derivatives have been proposed as important compounds for prebiotic peptide synthesis, and we demonstrate both a synthesis suggesting that they are potentially plausible components of a prebiotic inventory, and reactions showing their utility as abiotic precursors to a range of compounds of prebiological interest.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Comparison of Prebiotic Approaches to Dehydroalanine Nitrile Derivatives
NAI, N-acetylimidazole.
Figure 1
Figure 1
1H NMR spectrum showing the formation of major products FoSer-CN 2d, FoDHA-CN 3, and Fo(β-FoNH)Ala-CN 2e from the reaction between NaCN and glycolaldehyde 4d in formamide/formic acid after heating at 80 °C for 36 h. The two sets of alkenic peaks correspond to the two conformers of FoDHA-CN 2d, presumably due to restricted rotation about the amide C–N bond.
Scheme 2
Scheme 2. Preparative Route to FoDHA-CN
Scheme 3
Scheme 3. Reactions of FoDHA-CN 3 and Aqueous Cyanide
Scheme 4
Scheme 4. Reactions between FoDHA-CN 3 and Cyanide in Formamide
Scheme 5
Scheme 5. Reactions between Imidazole and FoDHA-CN 3 in Water and Formamide
See this image and copyright information in PMC

References

    1. Pascal R.; Boiteau L.; Commeyras A.. From the Prebiotic Synthesis of α-Amino Acids Towards a Primitive Translation Apparatus for the Synthesis of Peptides. Prebiotic Chemistry; Springer-Verlag: Berlin: pp 69–122.
    1. Strecker A. Ueber Die Künstliche Bildung Der Milchsäure Und Einen Neuen, Dem Glycocoll Homologen Körper. Ann. Chem. Pharm. 1850, 75, 27–45. 10.1002/jlac.18500750103. - DOI
    1. Bergs H.Hydantoin Derivatives. Patent DE566094, 1932.
    1. Pulletikurti S.; Yadav M.; Springsteen G.; Krishnamurthy R. Prebiotic Synthesis of α-Amino Acids and Orotate from α-Ketoacids Potentiates Transition to Extant Metabolic Pathways. Nat. Chem. 2021, 1142–1150. 10.1038/s41557-022-00999-w. - DOI - PubMed
    1. Hafenbradl D.; Keller M.; Wächtershäuser G.; Stetter K. O. Primordial Amino Acids by Reductive Amination of α-Oxo Acids in Conjunction with the Oxidative Formation of Pyrite. Tetrahedron Lett. 1995, 36, 5179–5182. 10.1016/0040-4039(95)01008-6. - DOI

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