Electrochemical strategies for peptide synthesis, deprotection and scalable reactor technologies
Review paper
DOI:
https://doi.org/10.5599/jese.3596Keywords:
Sustainable peptide manufacturing, peptide bonds formation, electrochemical deprotection, electrochemical reactor configurations, flow electrochemistryAbstract
Peptides have high target specificity, favourable safety profiles, and increasing applications in oncology, metabolic disorders, infectious diseases, and precision medicine, making them one of the fastest-growing classes of therapeutic molecules. Traditional peptide synthesis involves more hazardous solvents and stoichiometric quantities of coupling reagents, which lead to high process mass intensity and environmental impact. In electrochemical synthesis, electrons are traceless redox reagents that allow for the controlled activation and transformation of peptide substrates under mild conditions. Advances in electrochemical peptide bond formation, electrochemical deprotection methods, and new technologies of electrochemical reactors for peptide synthesis are critically discussed. The focus is on phosphine-mediated anodic peptide coupling, iodide-mediated amide formation, residue-selective electrochemical modifications and redox-triggered deprotection methods. Advances in flow electrochemistry, scalable reactor designs and sustainable peptide production methods are thoroughly discussed. The effect of electrochemical parameters such as the electrode materials, current density, solvent systems, electrolytes, reaction time, and reactor design on reaction efficiency and selectivity is critically evaluated. However, there are still some issues that need to be addressed, such as the scope of the substrates, the lack of understanding of the mechanisms, fouling of the electrodes, scalability and the absence of a standardized method of reporting. Opportunities for the future include the combination of electrochemistry and continuous-flow processing, sustainable solvent systems, automated synthesis platforms, and machine learning-assisted process optimization. Electrochemical approaches provide valuable potential for development of greener, more efficient and potentially scalable technology for next-generation pharmaceutical manufacturing of peptides.
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