Lijun Fan; Christopher P. Davie
ChemBioChem, 2017, 18(9), 843-847
https://doi.org/10.1002/cbic.201600563

Abstract

On‐DNA epoxide opening: We report zirconium tetrakis(dodecyl sulfate)‐catalyzed ring opening of on‐DNA epoxides in water with amines, including anilines. Cyclization of the resulting on‐DNA β‐amino alcohols leads to a variety of non‐aromatic heterocycles. A DNA encoded library of β‐amino alcohols and their cyclization products was assembled and screened against biological targets of interest.
Abstract
DNA-encoded library technology (ELT) has spurred wide interest in the pharmaceutical industry as a powerful tool for hit and lead generation. In recent years a number of “DNA-compatible” chemical modifications have been published and used to synthesize vastly diverse screening libraries. Herein we report a newly developed, zirconium tetrakis(dodecyl sulfate)[Zr(DS)4] catalyzed ring-opening of on-DNA epoxides in water with amines, including anilines. Subsequent cyclization of the resulting on-DNA b-amino alcohols leads to a variety of biologically interesting, nonaromatic heterocycles. Under these conditions, a library of 137 million on-DNA b-amino alcohols and their cyclization products was assembled