Enantiospecific synthesis of α-amino acid semialdehydes: a key step for the synthesis of unnatural unsaturated and saturated α-amino acids

Abstract

The enantiospecific synthesis of unnatural unsaturated and saturated α-amino acids based on a Wittig type reaction is described. The versatile synthetic intermediates, l-glutamic and l-aspartic acid semialdehydes, are obtained from the corresponding N, N-di-Boc-diesters, by the selective reduction of the ω-ester with DIBAL ® under controlled conditions. The semialdehydes are chemically stable for a prolonged time and react with various phosphorous ylides, under controlled conditions, to produce the enantiomerically pure unsaturated α-amino acids in high yields. The method is equally applicable to homologated diesters obtained by the presented methodology providing unsaturated amino acids with variable unsaturated positions and geometries. The corresponding saturated products can be obtained by simple hydrogenation.