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The self-disproportionation of enantiomers (SDE) of α-amino acid derivatives: facets of steric and electronic properties

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Abstract

α-Amino acids (α-AAs) are in extremely high demand in nearly every sector of the food and health-related chemical industries and continue to be the subject of intense multidisciplinary research. The self-disproportionation of enantiomers (SDE) is an emerging and one of the least studied areas of α-AA or enantiomeric properties, critically important for their production and application. In the present work, we report a detailed study of the SDE via achiral, gravity-driven column chromatography for a set of N-acylated, N-carbonylated, N-fluoroacylated, and N-thioacylated α-amino acid esters. As well as thioacylation, attention was paid to the effect of altering the R group of the ester functionality, the side chain, or that of the acyl group attached to the amide nitrogen, whereby it was found that electron-withdrawing groups in the latter moiety had a pronounced effect on the magnitude and behavior of the resulting SDE phenomenon. Intriguingly, in the case of N-fluoroacylated derivatives, by favoring the formation of dimeric associates and effecting a strong bias toward homochiral associates over heterochiral associates, the SDE magnitude was greatly reduced contrary to intuitive expectations. Energy estimates resulted from DFT calculations.

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Acknowledgements

The authors gratefully acknowledge financial support from the Ministry of Science and Higher Education, Poland (Grant no. 612 512, AW) and IKERBASQUE, the Basque Foundation for Science, Spain (VAS).

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Authors and Affiliations

  1. Department of Applied Chemistry, Shibaura Institute of Technology, 3-7-5 Toyosu, Kohto-ku, Tokyo, 135-8548, Japan

    Takuma Hosaka, Tomomi Imai & Osamu Kitagawa

  2. Institute of Chemistry, Jan Kochanowski University in Kielce, Świętokrzyska 15G, 25-406, Kielce, Poland

    Alicja Wzorek, Magdalena Marcinkowska & Anna Kolbus

  3. Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizábal 3, 20018, San Sebastián, Spain

    Alicja Wzorek & Vadim A. Soloshonok

  4. IKERBASQUE, Basque Foundation for Science, María Díaz de Haro 3. Plaza Bizkaia, 48013, Bilbao, Spain

    Vadim A. Soloshonok

  5. Molecular Structure Analysis, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Karel D. Klika

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  1. Takuma Hosaka
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  2. Tomomi Imai
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  7. Vadim A. Soloshonok
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Correspondence to Alicja Wzorek, Vadim A. Soloshonok or Karel D. Klika.

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Hosaka, T., Imai, T., Wzorek, A. et al. The self-disproportionation of enantiomers (SDE) of α-amino acid derivatives: facets of steric and electronic properties. Amino Acids 51, 283–294 (2019). https://doi.org/10.1007/s00726-018-2664-x

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