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Thermodynamic control of asymmetric amplification in amino acid catalysis

Naturevolume 441pages621623 (2006) | Download Citation

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Abstract

Ever since Pasteur noticed that tartrate crystals exist in two non-superimposable forms that are mirror images of one another—as are left and right hands—the phenomenon of chirality has intrigued scientists. On the molecular level, chirality often has a profound impact on recognition and interaction events and is thus important to biochemistry and pharmacology. In chemical synthesis, much effort has been directed towards developing asymmetric synthesis strategies that yield product molecules with a significant excess of either the left-handed or right-handed enantiomer. This is usually achieved by making use of chiral auxiliaries or catalysts that influence the course of a reaction, with the enantiomeric excess (ee) of the product linearly related to the ee of the auxiliary or catalyst used. In recent years, however, an increasing number of asymmetric reactions have been documented where this relationship is nonlinear1, an effect that can lead to asymmetric amplification. Theoretical models2,3 have long suggested that autocatalytic processes can result in kinetically controlled asymmetric amplification, a prediction that has now been verified experimentally4,5,6 and rationalized mechanistically7,8,9,10,11,12,13,14 for an autocatalytic alkylation reaction. Here we show an alternative mechanism that gives rise to asymmetric amplification based on the equilibrium solid-liquid phase behaviour of amino acids in solution. This amplification mechanism is robust and can operate in aqueous systems, making it an appealing proposition for explaining one of the most tantalizing examples of asymmetric amplification—the development of high enantiomeric excess in biomolecules from a presumably racemic prebiotic world.

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Acknowledgements

Funding from the EPSRC and AstraZeneca is gratefully acknowledged.

Author information

Author notes

    • Hiroshi Iwamura

    Present address: Mitsubishi Pharma, 14, Sunayama, Kamisu, Ibaraki, 314-0255, Japan

    • David H. Wells Jr

    Present address: University of Calgary, 2500 University Drive NW, Calgary AB, T2N 1N4, Canada

Affiliations

  1. Department of Chemistry

    • Martin Klussmann
    • , Hiroshi Iwamura
    • , Suju P. Mathew
    • , David H. Wells Jr
    • , Urvish Pandya
    • , Alan Armstrong
    •  & Donna G. Blackmond
  2. Department of Chemical Engineering and Chemical Technology, Imperial College, London, SW7 2AZ, UK

    • Donna G. Blackmond

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Competing interests

Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Corresponding author

Correspondence to Donna G. Blackmond.

Supplementary information

  1. Supplementary Notes

    This file contains Supplementary Methods, Supplementary Tables 1–5, Supplementary Figures 1 and 2 and Supplementary Equations 1 and 2. (PDF 101 kb)

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https://doi.org/10.1038/nature04780

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