ABSTRACT Amino acids are essential building blocks in biology and chemistry. Whereas nature relies on a small number of amino acid structures, chemists desire access to a vast range of

structurally diverse analogues1,2,3. 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 semisynthetic 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

possibilities for the late-stage modification of more complex oligopeptides. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS BIOMIMETIC 1,2-AMINO MIGRATION VIA PHOTOREDOX CATALYSIS Article Open access 07 March 2025

MODULAR AND DIVERSE SYNTHESIS OF AMINO ACIDS VIA ASYMMETRIC DECARBOXYLATIVE PROTONATION OF AMINOMALONIC ACIDS Article 16 November 2023 HARNESSING TRANSAMINASES TO CONSTRUCT AZACYCLIC

NON-CANONICAL AMINO ACIDS Article 28 March 2024 DATA AVAILABILITY All data supporting the findings of this paper are available in the main text or the Supplementary Information. REFERENCES *

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_Science_ 364, 681–685 (2019). Article  ADS  PubMed  PubMed Central  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank J. Yang (MIT) for HPLC separation of product 2P and

S. Garhwal (MIT) for supercritical fluid chromatography data collection. Financial support for this work was provided by the National Institutes of Health (GM146248) and the National Science

Foundation (NSF) through a Graduate Research Fellowship to G.O. (DGE1745303). AUTHOR INFORMATION Author notes * These authors contributed equally: Xin Gu, Yu-An Zhang AUTHORS AND

AFFILIATIONS * Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA Xin Gu, Yu-An Zhang, Shuo Zhang, Leon Wang, Xiyun Ye, Gino Occhialini, Jonah Barbour, 

Bradley L. Pentelute & Alison E. Wendlandt Authors * Xin Gu View author publications You can also search for this author inPubMed Google Scholar * Yu-An Zhang View author publications

You can also search for this author inPubMed Google Scholar * Shuo Zhang View author publications You can also search for this author inPubMed Google Scholar * Leon Wang View author

publications You can also search for this author inPubMed Google Scholar * Xiyun Ye View author publications You can also search for this author inPubMed Google Scholar * Gino Occhialini

View author publications You can also search for this author inPubMed Google Scholar * Jonah Barbour View author publications You can also search for this author inPubMed Google Scholar *

Bradley L. Pentelute View author publications You can also search for this author inPubMed Google Scholar * Alison E. Wendlandt View author publications You can also search for this author

inPubMed Google Scholar CONTRIBUTIONS A.E.W., X.G. and Y.-A.Z. conceived the work, designed experiments and analysed the data. L.W. and S.Z. contributed equally to substrate synthesis and

characterization. X.Y. and B.L.P. provided expertise on the synthesis and analysis of oligopeptides. G.O. and J.B. performed exploratory experiments establishing the feasibility of

terminal-selective aliphatic dehydrogenation. A.E.W., X.G. and Y.-A.Z. drafted the manuscript with input from all authors. A.E.W. directed the research. All authors have given approval to

the final version of the manuscript. CORRESPONDING AUTHOR Correspondence to Alison E. Wendlandt. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. PEER

REVIEW PEER REVIEW INFORMATION _Nature_ thanks Jonathan Clayden, Christopher Teskey and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. ADDITIONAL

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non-canonical amino acids through dehydrogenative tailoring. _Nature_ 634, 352–358 (2024). https://doi.org/10.1038/s41586-024-07988-8 Download citation * Received: 22 November 2023 *

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