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An Amphiphilic Polymer-Supported Strategy Enables Chemical Transformations Under Anhydrous Conditions for DNA-Encoded Library Synthesis

preprint
revised on 05.11.2019 and posted on 13.11.2019 by Yves Ruff, Roberto Martinez, Xavier Pellé, Pierre Nimsgern, Pascale Fille, Maxim Ratnikov, Frederic Berst
Herein, we describe the development of a practical catch-and release methodology utilizing a cationic, amphiphilic PEG-based polymer to perform chemical transformations on immobilized DNA conjugates under anhydrous conditions. We demonstrate the usefulness of our APTAC (amphiphilic polymer-facilitated transformations under anhydrous conditions) approach by performing several challenging transformations on DNA-conjugated small molecules in pure organic solvents: the addition of a carbanion equivalent to a DNA-conjugated ketone in tetrahydrofuran, the synthesis of saturated heterocycles using the tin (Sn) amine protocol (SnAP) in dichloromethane and the dual-catalytic (Ir/Ni) metallaphotoredox decarboxylative cross-coupling of carboxylic acids to DNA-conjugated aryl halides in DMSO. In addition, we demonstrate the feasibility of the latter in multititer-plate format.

History

Email Address of Submitting Author

frederic.berst@novartis.com

Institution

Novartis Institutes for Biomedical Research

Country

Switzerland

ORCID For Submitting Author

0000-0002-6673-3915

Declaration of Conflict of Interest

There are no conflicts of interest to declare.

Version Notes

version 3: APTAC for DEL, with additional references

Exports