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

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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.
Original languageEnglish
JournalEuropean Journal of Medicinal Chemistry
Pages (from-to)118-133
Number of pages16
Publication statusPublished - 2016

ID: 157952362