Synthesis of highly deuterated amino acids.

Since the discovery of deuterium,' there has been considerable interest in the preparation of a variety of compounds in which hydrogen has been replaced by this heavier isotope. Some of the research has centered around the synthesis of deuterated compounds for biological study.2 While not occupying a place of prominence in this work, the preparation of deuterated amino acids has been studied in a number of instances.36 Only the simplest of the amino acids, however, have been prepared in sufficient quantity and high isotopic purity to be broadly useful to the scientific community.7 8 The purpose of the present research is to provide the best possible syntheses of the common amino acids so that they may be obtained in quantity, high isotopic content, and at minimum cost. It is felt that these materials will then provide a new, basic tool useful for the exploration of a number of areas. The many ways in which deuterium-substituted amino acids can be used may be divided into two general categories. Deuterium can be used as a labeling agent to distinguish a molecule from its protio analogues.4' I Second, the kinetic isotope effect, which deuterium exhibits by virtue of its increased bonding strength, permits a more detailed study of specific mechanisms of amino acid reactions, e.g., transamination studies.9' 10 Although deuterium is a stable isotope and undetectable by radioactive tracer techniques, it is readily monitored by other common instrumental methods, thus making it extremely useful as a labeling agent. Through the characteristic behavior of a deuterium-substituted compound in infrared," proton magnetic resonance (pmr), 12 and mass spectroscopy, 3 it is possible to obtain a wide variety of information not readily available via simple radioactive tracers. Since amino acids are building blocks for many biological materials, studies on biosynthetic pathways might be facilitated through the use of deuterated amino acids as metabolites for living systems. The spectral properties of intermediates and products of a proposed biosynthetic route could then be compared with their protio analogues. Such an approach could result in detailed information on the role of a particular amino acid as a biosynthetic precursor.la3