香港大学黄重行团队报道了通过不对称脱羧氨基酸的质子化模块化和多样化合成氨基酸。相关研究成果发表在2023年11月16日出版的《自然—化学》。

立体选择性质子化是不对称催化中的一个挑战。质子的小尺寸和高转移率意味着很难控制面向平面中间体的选择性递送，但它可以解锁以前模糊的不对称转化。特别是，当与之前的脱羧反应偶联时，对映选择性质子化可以将丰富的酸原料转化为结构多样的手性分子。

该文中，锚定基团策略被证明是通过产生额外的催化剂-底物相互作用，来对催化剂传统结构修饰的潜在替代和补充。研究表明，氨基丙二酸中定制的苯甲酰胺基团可以帮助，与手性酸催化剂建立非共价相互作用的配位网络，包括氢键、π–π相互作用和分散力。这能够对映选择性脱羧质子化产生α-氨基酸。基于丙二酸的合成通过氨基丙二酸酯的简单取代引入侧链，从而可以获得结构和功能不同的氨基酸。

附：英文原文

Title: Modular and diverse synthesis of amino acids via asymmetric decarboxylative protonation of aminomalonic acids

Author: Zheng, Wei-Feng, Chen, Jingdan, Qi, Xiaotian, Huang, Zhongxing

Issue&Volume: 2023-11-16

Abstract: Stereoselective protonation is a challenge in asymmetric catalysis. The small size and high rate of transfer of protons mean that face-selective delivery to planar intermediates is hard to control, but it can unlock previously obscure asymmetric transformations. Particularly, when coupled with a preceding decarboxylation, enantioselective protonation can convert the abundant acid feedstocks into structurally diverse chiral molecules. Here an anchoring group strategy is demonstrated as a potential alternative and supplement to the conventional structural modification of catalysts by creating additional catalyst–substrate interactions. We show that a tailored benzamide group in aminomalonic acids can help build a coordinated network of non-covalent interactions, including hydrogen bonds, π–π interactions and dispersion forces, with a chiral acid catalyst. This allows enantioselective decarboxylative protonation to give α-amino acids. The malonate-based synthesis introduces side chains via a facile substitution of aminomalonic esters and thus can access structurally and functionally diverse amino acids.

DOI: 10.1038/s41557-023-01362-3

Source: https://www.nature.com/articles/s41557-023-01362-3