pH-Controlled Synthesis of Amino Acids Catalyzed by Transition Metal Aqua Complexes

环境意识的提高使得有必要在不使用氰化物等剧毒物质的情况下开发可持续的氨基酸合成方法。在这种背景下，酮酸的还原胺化反应值得特别关注，因为它与氨基酸与氨水化学选择性生物合成的途径非常相似，氨水是自然体系中必不可少的胺源。然而，在氨基酸的非酶合成中，迄今为止，催化还原胺化反应一直是在有机溶剂中使用氨以外的胺源进行的。因此，酮酸与氨水的催化还原胺化反应尚未实现。这种反应的困难主要是因为使用水作为反应介质。水介质必须足够酸性，才能使酮酸的羰基质子化。然而，质子的存在不仅会导致氢化物物种的分解，这将起到催化剂的作用，而且会导致al…的分解。更重要的是，通过酮酸的竞争转移氢化形成副产物羟基羧酸。我们研究了在酸性稳定的单核氢化物与氨水和HCOOY(Y=Na或H)在水中还原胺化商业上可用的酮酸合成氨基酸的高化学选择性。通过控制pH值，还原胺化反应适用于具有非极性、未荷电和带电取代基的三种主要氨基酸的高度化学选择性合成。这是第一个通过酮酸与氨水在水中催化还原氨化合成氨基酸的高化学选择性非酶合成法的例子。(15)N-氨和DCOONa分别是理想的胺和氢化物离子源，也可以很容易地实现与pH相关的(15)N-和D-双标记。因此，利用酸性稳定的氢化物络合物，在水中的最佳pH条件下，可以合成高化学选择性的氨基酸，而羟基羧酸的生成可以忽略不计。较少

Increasing environmental awareness makes it necessary to develop sustainable synthesis of amino acids without the use of highly toxic agents such as cyanides. In this context, reductive amination of keto acids has merited special attention, because it is a close laboratory analogy of a pathway by which amino acids are chemoselectively biosynthesized with aqueous ammonia that is an essential amine source in natural system. In nonenzymatic synthesis of amino acids, however, catalytic reductive amination has so far been carried out using amine sources other than ammonia in organic solvents. Thus, catalytic reductive amination of keto acids with aqueous ammonia has yet to be achieved. The difficulty of such reactions mainly arises from the use of water as a reaction media. The aqueous media must be acidic enough for the carbonyl group of keto acids to be protonated. However, the presence of proton causes not only the decomposition of a hydride species, which would act as a catalyst, but al … More so formation of the hydroxy carboxylic acids as a by-product by the competitive transfer hydrogenation of keto acids. We have investigated highly chemoselective synthesis of amino acids by reductive amination of commercially available keto acids, catalyzed by acid-stable mononuclear hydride complexes with aqueous ammonia and HCOOY (Y=Na or H) in water. The reductive amination is applicable to the highly chemoselective synthesis of all three major types of amino acids with nonpolar, uncharged polar, and charged polar substituents by controlling pH. This is the first example of highly chemoselective nonenzymatic synthesis of amino acid by catalytic reductive amination of keto acids with aqueous ammonia in water. pH-dependent (15)N- and D-double-labeling can also be readily accomplished by using (15)N-ammonia and DCOONa, which are ideal amine and hydride ion sources, respectively. Thus, the highly chemoselective synthesis of amino acids with negligible formation of hydroxy carboxylic acids has been made possible by using acid-stable hydride complexes under the optimized pH conditions in water. Less