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

13 June 2019, Version 2
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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.

Keywords

DNA-encoded libraries
DNA-compatible reactions
Photochemistry
Photoredox cross coupling
SNAP protocol

Supplementary materials

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ATAC for DELs v1
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Supporting information-ATAC for DEL-assembled v1
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ATAC for DELs v1
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