High-Throughput Solid-Phase Building Block Synthesis for DNA-Encoded Libraries

Claudio Zambaldo; Stefanie N. Geigle; Alexander L. Satz
Org. Lett., 2019, 21, 23, 9353-9357
https://doi.org/10.1021/acs.orglett.9b03553

Abstract

Herein we provide a generalizable method for the cost-effective synthesis of thousands of building blocks (BBs) employing DNA-incompatible chemistries. The ability to produce large numbers of crude products via solid-phase synthesis has existed for decades; however, our work demonstrates a practical use of such crude reaction mixtures and employs DNA-conjugation to simultaneously encode, purify, and rapidly analyze the desired products. This workflow generated sp3-rich BBs that could be encoded by DNA in a high-throughput manner.

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