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

TY - JOUR

T1 - Preparation and Application of an Inexpensive α‐Formylglycine Building Block Compatible with Fmoc Solid-Phase Peptide Synthesis

AU - Yates, Nicholas D.J.

AU - Warnes, Matthew E.

AU - Breetveld, Reuben

AU - Spicer, Christopher D.

AU - Signoret, Nathalie

AU - Fascione, Martin

N1 - 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.

PY - 2023/1/20

Y1 - 2023/1/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85146895208&partnerID=8YFLogxK

U2 - 10.1021/acs.orglett.2c04059

DO - 10.1021/acs.orglett.2c04059

M3 - Article

AN - SCOPUS:85146895208

SN - 1523-7060

JO - Organic Letters

JF - Organic Letters

ER -