{"title":"Access to Axially Chiral Biaryl Benzylamines via Ancestral Enzyme-Enabled Reductive Amination Desymmetrization","authors":"Wen-Qing Zheng, Xin-Xin Zhu, Zheng Zhu, Tairan Yang, Lifen Zheng, Rui Pan, Shenlin Wang, Lixin Zhang, Qi Chen, Jian-He Xu, Yongtao Xie, Gao-Wei Zheng","doi":"10.1021/acscatal.4c06881","DOIUrl":null,"url":null,"abstract":"Axially chiral biaryl benzylamines are present in numerous natural products, pharmaceuticals, chiral ligands, and catalysts. However, the direct catalytic synthesis of these functional molecules using a robust strategy remains a formidable challenge. Reductive amination desymmetrization of biaryl dialdehydes offers a powerful approach for the construction of axially chiral biaryl benzylamines but suffers from extensive undesirable side reactions. Herein, we engineered ancestral imine reductases to enable reductive amination desymmetrization of biaryl dialdehydes, allowing the construction of a wide range of axially chiral biaryl benzylamines with up to 99% conversion and 99% enantiomeric excess (ee). The ratio of the product to byproducts was up to 97:3 and over 90:10 in most cases. This work presents an alternative strategy for accessing axially chiral biaryl benzylamines and will stimulate the development of associated bioactive molecules and catalysts/ligands.","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":"21 1","pages":""},"PeriodicalIF":11.3000,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Catalysis ","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acscatal.4c06881","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Axially chiral biaryl benzylamines are present in numerous natural products, pharmaceuticals, chiral ligands, and catalysts. However, the direct catalytic synthesis of these functional molecules using a robust strategy remains a formidable challenge. Reductive amination desymmetrization of biaryl dialdehydes offers a powerful approach for the construction of axially chiral biaryl benzylamines but suffers from extensive undesirable side reactions. Herein, we engineered ancestral imine reductases to enable reductive amination desymmetrization of biaryl dialdehydes, allowing the construction of a wide range of axially chiral biaryl benzylamines with up to 99% conversion and 99% enantiomeric excess (ee). The ratio of the product to byproducts was up to 97:3 and over 90:10 in most cases. This work presents an alternative strategy for accessing axially chiral biaryl benzylamines and will stimulate the development of associated bioactive molecules and catalysts/ligands.
期刊介绍：
ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels.
The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.
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