Preparation and Application of an Inexpensive α‐Formylglycine Building Block Compatible with Fmoc Solid-Phase Peptide Synthesis

Abstract

α-Formylglycine (fGly) is a rare residue located in the active site of sulfatases and serves as a precursor to pharmaceutically relevant motifs. The installation of fGly motifs into peptides is currently challenging due to degradation under the acidic and nucleophile-rich conditions accompanying resin cleavage during solid-phase peptide synthesis. We report the synthesis of acid- and nucleophile-tolerant α-formylglycine building blocks from vitamin C and use them to prepare callyaerin A, a macrocyclic peptide containing an fGly-derived motif.

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Item Type:	Article
Authors/Creators:	Yates, Nicholas D.J. (nicholas.yates@york.ac.uk) Warnes, Matthew E. Breetveld, Reuben Spicer, Christopher D. https://orcid.org/0000-0001-8787-578X Signoret, Nathalie https://orcid.org/0000-0003-4977-4149 Fascione, Martin https://orcid.org/0000-0002-0066-4419
Copyright, Publisher and Additional Information:	Funding Information: We thank Dr. Ed Bergstrom and The York Centre of Excellence in Mass Spectrometry. The York Centre of Excellence in Mass Spectrometry was created thanks to a major capital investment through Science City York, supported by Yorkshire Forward with funds from the Northern Way Initiative, and subsequent support from EPSRC (EP/K039660/1; EP/M028127/1). This work was supported by The University of York, the EPSRC (summer vacation bursary for M.E.W. and EP/V044303/1) and UKRI (EP/X023680/1). Publisher Copyright: © 2023 The Authors. Published by American Chemical Society.
Dates:	Accepted: 19 January 2023 Published (online): 20 January 2023
Institution:	The University of York
Academic Units:	The University of York > Faculty of Sciences (York) > Chemistry (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York)
Funding Information:	Funder Grant number EUROPEAN COMMISSION 101044024 EPSRC EP/V044303/1
Depositing User:	Pure (York)
Date Deposited:	23 Jan 2023 11:40
Last Modified:	20 Sep 2025 01:57
Published Version:	https://doi.org/10.1021/acs.orglett.2c04059
Status:	Published online
Refereed:	Yes
Identification Number:	10.1021/acs.orglett.2c04059
Related URLs:	http://www.scopus.com/inward/record.url?...
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:195580

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Preparation and Application of an Inexpensive α‐Formylglycine Building Block Compatible with Fmoc Solid-Phase Peptide Synthesis

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