Issue 7, 2016

Development and design of the tertiary amino effect reaction for DNA-encoded library synthesis

Abstract

The generation of novel chemical leads for clinical development is a constant challenge in the pharmaceutical industry. The synthesis of DNA-encoded libraries has emerged as a powerful method for hit and lead generation. We report the development of the tertiary amino effect reaction on DNA-tethered substrates. A variety of ortho-dialkylaminoaryl aldehydes undergo a cascade reaction involving a Knoevenagel condensation, a [1,5]-hydride shift, and a Mannich cyclization to give diversely substituted spirocycles. NMR analysis of substrates bearing an enriched double-13C label confirmed product formation. The net formation of two carbon–carbon bonds adds to the few examples of carbon–carbon forming reactions performed in presence of DNA-encoding systems.

Graphical abstract: Development and design of the tertiary amino effect reaction for DNA-encoded library synthesis

Supplementary files

Article information

Article type
Research Article
Submitted
12 Feb 2016
Accepted
06 Apr 2016
First published
08 Apr 2016

Med. Chem. Commun., 2016,7, 1316-1322

Development and design of the tertiary amino effect reaction for DNA-encoded library synthesis

X. Tian, G. S. Basarab, N. Selmi, T. Kogej, Y. Zhang, M. Clark and R. A. Goodnow Jr., Med. Chem. Commun., 2016, 7, 1316 DOI: 10.1039/C6MD00088F

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