Tailored amination enables switchable synthesis of α- and γ-amino acid derivatives from extended quinone methides

Abstract Unnatural α- and γ-amino acids display a diverse range of biological activities and serve as crucial intermediates in pharmaceutical production. Specifically, the synthesis of such molecules has been highly sought after in both academia and industry. Nevertheless, their direct synthesis fro...

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Main Authors: Chao-Gang Zhang, Yu-Ping Tang, Qingqin Huang, Yong-Ke Qiu, Hailong Yan, Lei Dai
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60749-7
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author Chao-Gang Zhang
Yu-Ping Tang
Qingqin Huang
Yong-Ke Qiu
Hailong Yan
Lei Dai
author_facet Chao-Gang Zhang
Yu-Ping Tang
Qingqin Huang
Yong-Ke Qiu
Hailong Yan
Lei Dai
author_sort Chao-Gang Zhang
collection DOAJ
description Abstract Unnatural α- and γ-amino acids display a diverse range of biological activities and serve as crucial intermediates in pharmaceutical production. Specifically, the synthesis of such molecules has been highly sought after in both academia and industry. Nevertheless, their direct synthesis from simple bulk feedstocks has remained largely unexplored, and the switchable synthesis of α- and γ-amino acids through a shared intermediate has never been documented. We disclose herein a four-component reaction involving readily available bulk chemicals to facilitate the switchable synthesis of α- and γ-amino acids from a shared extended p-quinone methide through a tailored amination strategy. A diverse array of amines, including several unmodified drug molecules, along with various other nucleophiles, are readily utilized as suitable substrates in this reaction. We believe this work could inspire future intensive efforts toward the switchable synthesis of amino acids in a practical and efficient manner.
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institution Kabale University
issn 2041-1723
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publishDate 2025-07-01
publisher Nature Portfolio
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series Nature Communications
spelling doaj-art-419fef7cc2ac4ea896183d3d43a89d0a2025-08-20T03:45:35ZengNature PortfolioNature Communications2041-17232025-07-0116111010.1038/s41467-025-60749-7Tailored amination enables switchable synthesis of α- and γ-amino acid derivatives from extended quinone methidesChao-Gang Zhang0Yu-Ping Tang1Qingqin Huang2Yong-Ke Qiu3Hailong Yan4Lei Dai5Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing UniversityChongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing UniversityChongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing UniversityChongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing UniversityChongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing UniversityChongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing UniversityAbstract Unnatural α- and γ-amino acids display a diverse range of biological activities and serve as crucial intermediates in pharmaceutical production. Specifically, the synthesis of such molecules has been highly sought after in both academia and industry. Nevertheless, their direct synthesis from simple bulk feedstocks has remained largely unexplored, and the switchable synthesis of α- and γ-amino acids through a shared intermediate has never been documented. We disclose herein a four-component reaction involving readily available bulk chemicals to facilitate the switchable synthesis of α- and γ-amino acids from a shared extended p-quinone methide through a tailored amination strategy. A diverse array of amines, including several unmodified drug molecules, along with various other nucleophiles, are readily utilized as suitable substrates in this reaction. We believe this work could inspire future intensive efforts toward the switchable synthesis of amino acids in a practical and efficient manner.https://doi.org/10.1038/s41467-025-60749-7
spellingShingle Chao-Gang Zhang
Yu-Ping Tang
Qingqin Huang
Yong-Ke Qiu
Hailong Yan
Lei Dai
Tailored amination enables switchable synthesis of α- and γ-amino acid derivatives from extended quinone methides
Nature Communications
title Tailored amination enables switchable synthesis of α- and γ-amino acid derivatives from extended quinone methides
title_full Tailored amination enables switchable synthesis of α- and γ-amino acid derivatives from extended quinone methides
title_fullStr Tailored amination enables switchable synthesis of α- and γ-amino acid derivatives from extended quinone methides
title_full_unstemmed Tailored amination enables switchable synthesis of α- and γ-amino acid derivatives from extended quinone methides
title_short Tailored amination enables switchable synthesis of α- and γ-amino acid derivatives from extended quinone methides
title_sort tailored amination enables switchable synthesis of α and γ amino acid derivatives from extended quinone methides
url https://doi.org/10.1038/s41467-025-60749-7
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