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Lookup NU author(s): Jake Odger, Matt Anderson, Thomas Carton, Professor Mike WaringORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
DNA-encoded libraries are increasingly important in hit identification at the early stage of the drug discovery process. The approach relies on efficient methods for synthesis of drug-like compounds attached to coding DNA sequences. Many reactions employed for library synthesis are inefficient and result in significant DNA-damage, incomplete conversion and the formation of side products, which compromise the fidelity of the resulting library. We have developed a wide array of reactions that are promoted by the micelle-forming surfactant TPGS-750-M that address these issues and lead to improved efficiency. Here we demonstrate further improvements to key reactions Suzuki-Miyaura coupling, reductive amination and amide coupling by surfactant screening using principal component-based surfactant maps which lead to improved conversion for problematic substrates. This work demonstrates the utility of surfactant maps in reaction optimisation for DNA-encoded library synthesis and leads to further improvements in these important transformations.
Author(s): Odger J, Anderson MJ, Carton TP, Nguyen B, Foote K, Waring MJ
Publication type: Article
Publication status: Published
Journal: Organic and Biomolecular Chemistry
Year: 2025
Volume: 23
Issue: 28
Pages: 6745-6754
Print publication date: 28/07/2025
Online publication date: 13/06/2025
Acceptance date: 13/06/2025
Date deposited: 26/06/2025
ISSN (print): 1477-0520
ISSN (electronic): 1477-0539
Publisher: Royal Society of Chemistry
URL: https://doi.org/10.1039/D5OB00864F
DOI: 10.1039/D5OB00864F
Data Access Statement: Full supporting data and experimental details of this study are available within the article and the ESI.†
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