Xin Gu, Yu-An Zhang, Shuo Zhang, Leon Wang, Xiyun Ye, Gino Occhialini, Jonah Barbour, Bradley L. Pentelute, Alison E. Wendlandt
{"title":"Synthesis of non-canonical amino acids through dehydrogenative tailoring","authors":"Xin Gu, Yu-An Zhang, Shuo Zhang, Leon Wang, Xiyun Ye, Gino Occhialini, Jonah Barbour, Bradley L. Pentelute, Alison E. Wendlandt","doi":"10.1038/s41586-024-07988-8","DOIUrl":null,"url":null,"abstract":"<p>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 analogs<sup>1–3</sup> 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 developed<sup>4,5</sup> 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.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":null,"pages":null},"PeriodicalIF":50.5000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41586-024-07988-8","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Nature is a prestigious international journal that publishes peer-reviewed research in various scientific and technological fields. The selection of articles is based on criteria such as originality, importance, interdisciplinary relevance, timeliness, accessibility, elegance, and surprising conclusions. In addition to showcasing significant scientific advances, Nature delivers rapid, authoritative, insightful news, and interpretation of current and upcoming trends impacting science, scientists, and the broader public. The journal serves a dual purpose: firstly, to promptly share noteworthy scientific advances and foster discussions among scientists, and secondly, to ensure the swift dissemination of scientific results globally, emphasizing their significance for knowledge, culture, and daily life.