Chemical Deuteration of α-Amino Acids and Optical Resolution: Overview of Research Developments.

Abstract

Deuterium-labelled amino acids have found extensive applications in such research areas as pharmaceutical, bioanalytical, neutron diffraction, inelastic neutron scattering, in analysis of drug metabolism using mass spectrometry (MS), and, structuring of biomolecules by NMR. For these reasons, interest in new methodologies for the deuterium labelling of amino acids and the extent of their applications are equally rising. The ideal method will be able to label target compounds rapidly and cost-effectively by the direct exchange of a hydrogen atom by a deuterium atom. Most of these exchange reactions can often be carried out directly on the final target compound or a late intermediate in the synthesis, and often D₂O can be used as the deuterium source. This review aims to provide a high-level overview of the chemical deuteration of amino acids in various groups (aromatic, heterocyclic, and non-aromatic α-amino acids). It primarily focuses on metal-catalyzed H/D exchange under hydrothermal conditions, with some attention given to studies on stereoselectivity and chemically synthesized perdeuteration and selective deuteration. In addition, we present different methods tested, manipulated, and developed for versatile new scalable protocols for preparation of selective and perdeuterated biologically important amino acids and their enzymatic and kinetic resolution to give pure enantiomers. Different methods for the synthesis of stereocontrolled selective and perdeuterated amino acids, including synthetic, and methods for preparing optically pure amino acids are presented.