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Lookup NU author(s): Harriet Stanway-Gordon,
Professor Mike Waring
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
DNA-encoded libraries (DELs) are an increasingly popular approach to finding small molecule ligands for proteins. Many DEL synthesis protocols hinge on sequential additions of monomers using split-pool combinatorial methods. Therefore, compatible protecting group strategies that allow the unmasking of reactive functionality (e.g. amines and alcohols) prior to monomer coupling, or the removal of less desirable functionality (e.g., alkenes and alkynes) are highly desirable. Hydrogenation / hydrogenolysis procedures would achieve these ends but have not been amenable to DEL chemistry. We report a catalytic hydrogen transfer reaction using Pd / C, HCONH4 and the micelle-forming surfactant, TPGS-750-M, which gives highly efficient conversions for hydrogenolysis of Cbz-protected amines and benzyl protected alcohols and hydrogenation of nitros, halides, nitriles, aldehydes, alkenes and alkynes. Application to multicycle synthesis of an encoded compound was fully compatible with DNA-amplification and sequencing, demonstrating its applicability to DEL synthesis. This method will enable synthetic DEL sequences using orthogonal protecting groups.
Author(s): Stanway-Gordon HA, Graham JS, Waring MJ
Publication type: Article
Publication status: Published
Journal: Angewandte Chemie International Edition
Print publication date: 10/01/2022
Online publication date: 08/11/2021
Acceptance date: 08/11/2021
Date deposited: 16/11/2021
ISSN (print): 0044-8249
ISSN (electronic): 1521-3757
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