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

随着环境意识的提高，有必要在不使用氰化物等高毒性试剂的情况下开发可持续的氨基酸合成。在这种情况下，酮酸的还原胺化值得特别关注，因为它是一个密切的实验室模拟的途径，通过该途径，氨基酸是化学选择性生物合成与氨水，这是一种必需的胺源在自然系统中。然而，在氨基酸的非酶促合成中，迄今为止，催化还原胺化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尚未实现。这种反应的困难主要来自于使用水作为反应介质。水性介质必须足够酸性以使酮酸的羰基质子化。然而，质子的存在不仅导致氢化物分解，这将作为催化剂，而且还导致氢化物分解。 关于我们 因此通过酮酸的竞争性转移氢化形成作为副产物的羟基羧酸。我们已经研究了高度化学选择性的合成氨基酸的还原胺化的市售酮酸，催化的酸稳定的单核氢化物配合物与氨水和HCOOY（Y=Na或H）在水中。还原胺化适用于所有三种主要类型的氨基酸与非极性，不带电的极性，和带电的极性取代基通过控制pH值的高度化学选择性合成。这是第一个例子的高度化学选择性非酶合成氨基酸的酮酸与氨水在水中的催化还原胺化。pH依赖性（15）N-和D-双标记也可以通过使用（15）N-氨和DCOONa容易地实现，它们分别是理想的胺和氢化物离子源。因此，通过在优化的pH条件下在水中使用酸稳定的氢化物络合物，可以高度化学选择性地合成氨基酸，而羟基羧酸的形成可以忽略不计。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