Thermodynamic control of asymmetric amplification in amino acid catalysis
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 nonlinear, an effect that can lead to asymmetric amplification. Theoretical models have long suggested that autocatalytic processes can result in kinetically controlled asymmetric amplification, a prediction that has now been verified experimentally and rationalized mechanistically 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…
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The aldol reaction between 2-chlorobenzaldehyde and acetone exhibits a strongly positive non-linear effect, i.e. the e.e. in the aldol product is drastically higher than expected from the optical purity of the engaged amino acid catalyst.
“The aldol reaction between 2-chlorobenzaldehyde and acetone was found to exhibit a strongly positive non-linear effect, i.e. the e.e. in the aldol product is drastically higher than that expected from the optical purity of the engaged amino acid catalyst.497”
From Possible chemical and physical scenarios towards biological homochirality (2022) · cites this paper as [497]
Serine is the most striking example of SDE because a virtually enantiopure solution (>99% e.e.) is obtained at 25 degrees C under solid-liquid equilibrium conditions starting from a 1% e.e. mixture only.
“Serine is the most striking example since a virtually enantiopure solution (499% e.e.) is obtained at 25 1C under solid-liquid equilibrium conditions starting from a 1% e.e. mixture only.497”
From Possible chemical and physical scenarios towards biological homochirality (2022) · cites this paper as [497]
Several proteinogenic amino acids form relatively insoluble D:L crystals and therefore show high eutectic ee values.
“Several of the proteinogenic amino acids form relatively insoluble D:L crystals and therefore show high eutectic ee values.”
From The Origin of Biological Homochirality (2010) · cites this paper as Klussmann et al. 2006
Serine's eutectic occurs at >99% ee.
“For example, serine's eutectic occurs at . 99% ee.”
From The Origin of Biological Homochirality (2010) · cites this paper as Klussmann et al. 2006
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- Authors
- Klussmann, M., Iwamura, H., Mathew, S. P., Wells, D. H., Pandya, U., Armstrong, A., & Blackmond, D. G.
- Affiliations
- Imperial College London (GB)
- University of Calgary (CA)
- Corresponding author
- Blackmond, Donna G.
- Venue
- Nature
- Published
- 2006-06
- Volume
- 441
- Issue
- 7093
- Pages
- 621-623
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1980949293
- Cited by
- 396
- References
- 3
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 9 · 2023: 11 · 2022: 13 · 2021: 16 · 2020: 16 · 2019: 13 · 2018: 20 · 2017: 13 · 2016: 13 · 2015: 11 · 2014: 25 · 2013: 19 · 2012: 21
- FWCI
- 20.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- AstraZeneca
- Engineering and Physical Sciences Research Council
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Physical Sciences › Chemistry › Organic Chemistry › Asymmetric Synthesis and Catalysis
- Physical Sciences › Chemistry › Organic Chemistry › Chemistry and Stereochemistry Studies
- Keywords
- asymmetric amplification, amino acid catalysis, chirality, enantiomeric excess, autocatalysis, asymmetric synthesis, thermodynamic control, enantiomeric excess amplification
- MeSH terms
- Aldehydes, Alkylation, Amino Acids, Catalysis, Kinetics, Proline, Stereoisomerism, Thermodynamics, Water
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