Solvent‐Enabled Selective Electrochemical Decarboxylative Acetoxylation of Fmoc‐Protected Peptides
The synthesis of peptide‐based linkers for antibody‐drug conjugates involves an oxidative decarboxylation step. Traditional Hofer–Moest electrolysis conditions are not suitable to achieve this transformation due to the presence of an oxidatively labile Fmoc‐protecting group. Herein, a solvent‐enabled electrochemical procedure has been established, whereby the solvent electrochemical window prevents degradation of the protecting group. The method has been demonstrated for several relevant peptides in good to very good yields (64–92%).
Authors
- Paul Hanselmann
- Ryan Littich
- Dominique M. Roberge (ORCID: https://orcid.org/0000-0003-2462-5067)
- David Cantillo (ORCID: https://orcid.org/0000-0001-7604-8711)
- Simon Wagschal (ORCID: https://orcid.org/0000-0003-1979-5838)
- C. Oliver Kappe (ORCID: https://orcid.org/0000-0003-2983-6007)
- Michaël Bersier
- Clara Bovino
- David M. Köpfler
Institutions
- The University of Queensland (AU)
- Graz University of Technology (AT)
- Research Center Pharmaceutical Engineering (Austria) (AT)
- Lonza (Switzerland) (CH)
Publication Details
- Journal
- ChemElectroChem
- Published
- 2025-08-29
- DOI
- https://doi.org/10.1002/celc.202500308
- Citations
- 1
- Primary Topic
- Chemical Synthesis and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Royal College of Physicians of Edinburgh
- University of Queensland
- Karl-Franzens-Universität Graz
- Bundesministerium für Digitalisierung und Wirtschaftsstandort