Iminolactones as Tools for Inversion of the Absolute Configuration of alpha-Amino Acids and as Inhibitors of Cancer Cell Proliferation

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Iminolactones as Tools for Inversion of the Absolute Configuration of alpha-Amino Acids and as Inhibitors of Cancer Cell Proliferation. / Jensen, Christina Mernøe; Chow, Hsiao-Qing; Chen, Ming; Zhai, Lin; Frydenvang, Karla Andrea; Liu, Huizhen ; Franzyk, Henrik; Christensen, Søren Brøgger.

In: European Journal of Medicinal Chemistry, Vol. 114, 2016, p. 118-133.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Jensen, CM, Chow, H-Q, Chen, M, Zhai, L, Frydenvang, KA, Liu, H, Franzyk, H & Christensen, SB 2016, 'Iminolactones as Tools for Inversion of the Absolute Configuration of alpha-Amino Acids and as Inhibitors of Cancer Cell Proliferation', European Journal of Medicinal Chemistry, vol. 114, pp. 118-133. https://doi.org/10.1016/j.ejmech.2016.02.037

APA

Jensen, C. M., Chow, H-Q., Chen, M., Zhai, L., Frydenvang, K. A., Liu, H., ... Christensen, S. B. (2016). Iminolactones as Tools for Inversion of the Absolute Configuration of alpha-Amino Acids and as Inhibitors of Cancer Cell Proliferation. European Journal of Medicinal Chemistry, 114, 118-133. https://doi.org/10.1016/j.ejmech.2016.02.037

Vancouver

Jensen CM, Chow H-Q, Chen M, Zhai L, Frydenvang KA, Liu H et al. Iminolactones as Tools for Inversion of the Absolute Configuration of alpha-Amino Acids and as Inhibitors of Cancer Cell Proliferation. European Journal of Medicinal Chemistry. 2016;114:118-133. https://doi.org/10.1016/j.ejmech.2016.02.037

Author

Jensen, Christina Mernøe ; Chow, Hsiao-Qing ; Chen, Ming ; Zhai, Lin ; Frydenvang, Karla Andrea ; Liu, Huizhen ; Franzyk, Henrik ; Christensen, Søren Brøgger. / Iminolactones as Tools for Inversion of the Absolute Configuration of alpha-Amino Acids and as Inhibitors of Cancer Cell Proliferation. In: European Journal of Medicinal Chemistry. 2016 ; Vol. 114. pp. 118-133.

Bibtex

@article{3b0e5d9705884b478bd88a565e81fbc3,
title = "Iminolactones as Tools for Inversion of the Absolute Configuration of alpha-Amino Acids and as Inhibitors of Cancer Cell Proliferation",
abstract = "A library of iminolactones was prepared by esterification of several 2-hydroxyketones, of which some were of terpenoid origin while others were obtained via synthesis, with a number of N-protected D- and L--amino acids. After N-deprotection of the intermdiate esters, the free amines spontaneously underwent condensation with the ketone to form iminolactones. Esters of (1S,2S,5S)-2-hydroxypinan-3-one with both D- and L--amino acids were partially epimerized at the -carbon atom to give a diasteromeric ester mixture. Only iminolactones of the L-amino acid were formed after cyclization of (1S,2S,5S)-2-hydroxypinan-3-one, and correspondingly only D-amino acid iminolactones were formed after reaction with (1R,2R,5R)-2-hydroxypinan-3-one. The protocol thus enables inversion of the absolute configuration of amino acids. Some members of the prepared library of iminolactones displayed significant anti-proliferative effects toward three cancer cell lines (EL4, MCF7, PC3) with insignificant effect on non-malign cell lines (McCoy, MCF10A, NIH3T3). Thus, iminolactones appear to be potential lead structures for preparation of drugs selectively affecting proliferation of malign cell lines.",
keywords = "The Faculty of Pharmaceutical Sciences, Iminolactones, Inversion of amino acids, Anti-proliferative effects, Selective inhibition",
author = "Jensen, {Christina Mern{\o}e} and Hsiao-Qing Chow and Ming Chen and Lin Zhai and Frydenvang, {Karla Andrea} and Huizhen Liu and Henrik Franzyk and Christensen, {S{\o}ren Br{\o}gger}",
year = "2016",
doi = "10.1016/j.ejmech.2016.02.037",
language = "English",
volume = "114",
pages = "118--133",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson",

}

RIS

TY - JOUR

T1 - Iminolactones as Tools for Inversion of the Absolute Configuration of alpha-Amino Acids and as Inhibitors of Cancer Cell Proliferation

AU - Jensen, Christina Mernøe

AU - Chow, Hsiao-Qing

AU - Chen, Ming

AU - Zhai, Lin

AU - Frydenvang, Karla Andrea

AU - Liu, Huizhen

AU - Franzyk, Henrik

AU - Christensen, Søren Brøgger

PY - 2016

Y1 - 2016

N2 - A library of iminolactones was prepared by esterification of several 2-hydroxyketones, of which some were of terpenoid origin while others were obtained via synthesis, with a number of N-protected D- and L--amino acids. After N-deprotection of the intermdiate esters, the free amines spontaneously underwent condensation with the ketone to form iminolactones. Esters of (1S,2S,5S)-2-hydroxypinan-3-one with both D- and L--amino acids were partially epimerized at the -carbon atom to give a diasteromeric ester mixture. Only iminolactones of the L-amino acid were formed after cyclization of (1S,2S,5S)-2-hydroxypinan-3-one, and correspondingly only D-amino acid iminolactones were formed after reaction with (1R,2R,5R)-2-hydroxypinan-3-one. The protocol thus enables inversion of the absolute configuration of amino acids. Some members of the prepared library of iminolactones displayed significant anti-proliferative effects toward three cancer cell lines (EL4, MCF7, PC3) with insignificant effect on non-malign cell lines (McCoy, MCF10A, NIH3T3). Thus, iminolactones appear to be potential lead structures for preparation of drugs selectively affecting proliferation of malign cell lines.

AB - A library of iminolactones was prepared by esterification of several 2-hydroxyketones, of which some were of terpenoid origin while others were obtained via synthesis, with a number of N-protected D- and L--amino acids. After N-deprotection of the intermdiate esters, the free amines spontaneously underwent condensation with the ketone to form iminolactones. Esters of (1S,2S,5S)-2-hydroxypinan-3-one with both D- and L--amino acids were partially epimerized at the -carbon atom to give a diasteromeric ester mixture. Only iminolactones of the L-amino acid were formed after cyclization of (1S,2S,5S)-2-hydroxypinan-3-one, and correspondingly only D-amino acid iminolactones were formed after reaction with (1R,2R,5R)-2-hydroxypinan-3-one. The protocol thus enables inversion of the absolute configuration of amino acids. Some members of the prepared library of iminolactones displayed significant anti-proliferative effects toward three cancer cell lines (EL4, MCF7, PC3) with insignificant effect on non-malign cell lines (McCoy, MCF10A, NIH3T3). Thus, iminolactones appear to be potential lead structures for preparation of drugs selectively affecting proliferation of malign cell lines.

KW - The Faculty of Pharmaceutical Sciences

KW - Iminolactones, Inversion of amino acids, Anti-proliferative effects, Selective inhibition

U2 - 10.1016/j.ejmech.2016.02.037

DO - 10.1016/j.ejmech.2016.02.037

M3 - Journal article

VL - 114

SP - 118

EP - 133

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

ER -

ID: 157952362