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Micelle-Promoted Reductive Amination of DNA-Conjugated Amines for DNA-Encoded Library Synthesis

Lookup NU author(s): Matt Anderson, Thomas Carton, Catherine Salvini, Professor Mike Waring

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

DNA-encoded libraries (DELs) have become a leading technology for hit identification in drug discovery projects as large, diverse libraries can be generated. DELs are commonly synthesised via split-and-pool methodology; thus, chemical transformations utilised must be highly efficient, proceeding with high conversions. Reactions performed in DEL synthesis also require a broad substrate scope to produce diverse, drug-like libraries. Many pharmaceutical compounds incorporate multiple C-N bonds, over a quarter of which are synthesised via reductive aminations. However, few on-DNA reductive amination procedures have been developed. Herein is reported the application of the micelle-forming surfactant, TPGS-750-M, to the on-DNA reductive amination of DNA-conjugated amines, yielding highly efficient conversions with a broad range of aldehydes, including medicinally relevant heterocyclic and aliphatic substrates. The procedure is compatible with DNA amplification and sequencing, demonstrating its applicability to DEL synthesis.

Publication metadata

Author(s): Anderson MJ, Carton T, Salvini CLA, Crawford JJ, Pairaudeau G, Waring MJ

Publication type: Article

Publication status: Published

Journal: Chemistry: A European Journal

Year: 2024

Volume: 30

Issue: 21

Print publication date: 11/04/2024

Online publication date: 22/01/2024

Acceptance date: 22/01/2024

Date deposited: 22/01/2024

ISSN (print): 1521-3765

ISSN (electronic): 0947-6539

Publisher: Wiley-VCH Verlag GmbH & Co. KGaA

URL: https://doi.org/10.1002/chem.202400239

DOI: 10.1002/chem.202400239

ePrints DOI: 10.57711/mm0a-h680

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