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

preprint
revised on 02.09.2019, 11:36 and posted on 04.09.2019, 17:14 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