美国麻省理工学院Wendlandt, Alison E.团队报道了脱氢剪裁法合成非规范氨基酸。相关研究成果于2024年8月29日发表在国际顶尖学术期刊《自然》。

氨基酸是生物学和化学中必不可少的组成部分。虽然自然界依赖于少量的氨基酸结构，但化学家希望获得广泛的结构多样的类似物。氨基酸侧链残基的选择性修饰，是获得化学和生物学中有价值的非规范衍生物的有效策略。

虽然利用极性和芳香族氨基酸中发现的官能团的半合成方法，已经得到了广泛的探索，但转化脂肪族氨基酸中未活化的C-H键的高度选择性和通用方法仍然不太发达。

该文中，研究人员公开了一种将脂族氨基酸转化为结构多样的类似物的逐步脱氢方法。这种方法成功的关键在于，开发一种由光化学照射驱动的选择性催化无受体脱氢方法，该方法为下游官能化提供了获得末端烯烃中间体的途径。总体而言，该策略能够快速合成新的氨基酸构建块，并为更复杂的寡肽的后期修饰提供了可能性。

附：英文原文

Title: Synthesis of non-canonical amino acids through dehydrogenative tailoring

Author: Gu, Xin, Zhang, Yu-An, Zhang, Shuo, Wang, Leon, Ye, Xiyun, Occhialini, Gino, Barbour, Jonah, Pentelute, Bradley L., Wendlandt, Alison E.

Issue&Volume: 2024-08-29

Abstract: Amino acids are essential building blocks in biology and chemistry. While nature relies on a small number of amino acid structures, chemists desire access to a vast scope of structurally diverse analogs1–3 The selective modification of amino acid side-chain residues represents an efficient strategy to access non-canonical derivatives of value in chemistry and biology. While semi-synthetic methods leveraging the functional groups found in polar and aromatic amino acids have been extensively explored, highly selective and general approaches to transform unactivated C–H bonds in aliphatic amino acids remain less developed4,5 Here, we disclose a stepwise dehydrogenative method to convert aliphatic amino acids into structurally diverse analogs. The key to the success of this approach lies in the development of a selective catalytic acceptorless dehydrogenation method driven by photochemical irradiation, which provides access to terminal alkene intermediates for downstream functionalization. Overall, this strategy enables the rapid synthesis of new amino acid building blocks and suggests possibilities for the late-stage modification of more complex oligopeptides.

DOI: 10.1038/s41586-024-07988-8

Source: https://www.nature.com/articles/s41586-024-07988-8