Principles and Results of Stable Isotope Labelling of L-α-Aminoacids by Combined Chemical and Enzymatic Methods

Abstract

Abstract The major routes for making aminoacids and their isotopomers described in the literature are briefly compiled, especially considering about fourty research papers from the last five years. This report concentrates on the introduction of 2H, 13C, 15N, 17O and 18O into different defined positions of L-α-aminoacids. A scheme of four reaction categories with flowcharts is presented (homologation reactions with labelled cyanide and acetate; α-homologation of labeled glycine; β-homologation and/or amination of labelled alanine equivalents and α-enoic acids, including side chain modifications; and reductive amination and transamination of labelled α-ketoacids). The labelling studies done here include the 1-13C substitution of α-ketoacids by the trimethylsilyl cyanide method, the glycine isotopomer homologation by the azlactone and hydantoin methods, the enzymatic aryl and/or ammonia addition to pyruvate and α-enoic acids, and the enzymatic reductive amination of α-ketoacids under enzymatic or enzymo—electrochemical NAD+ recycling. Summarizing the state of the art, the most promising concepts for the 13C and 15N introduction into the 1- and/or 2-positions (backbone labeling) are those starting from labelled glycine. Labelled side-chain synthons can be fused to achiral and chiral glycine and alanine equivalents by asymmetric chemical substitutions and enzymatic lyase reactions. The L-configuration of the labelled aminoacids can be achieved by acylase or oxidase-transaminase based racemate resolutions, asymmetric chemical syntheses, enzymatic reductive aminations or transaminations, and hydantoinase catalyzed reactions.