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

Nicholas D.J. Yates*, Matthew E. Warnes, Reuben Breetveld, Christopher D. Spicer, Nathalie Signoret, Martin Fascione

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Number of pages5
JournalOrganic Letters
Early online date20 Jan 2023
Publication statusE-pub ahead of print - 20 Jan 2023

Bibliographical note

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.

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