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

MedChemComm Pub Date: 2016-04-08 DOI: 10.1039/C6MD00088F

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
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