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

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.