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SYNTHETIC METHODOLOGY

Decorating and diversifying drugs

Nature Chemistry volume 12, pages 505–506 (2020)Cite this article

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The direct conversion of lead compounds into potentially more potent derivatives, through selective functionalization, could help to speed up the discovery of drug candidates. Now, a method has been reported that enables the late-stage C–H methylation of complex drug-like molecules, using a sustainable cobalt-based catalyst.

The pharmaceutical industry is continuously looking to supplement their synthetic toolbox with innovative methodologies readily applicable to large panels of drug-like molecules. Although the C–H activation approach is perfectly suited for late-stage functionalization, such transformations generally require accommodation on a substrate with a Lewis basic site, in charge of the coordination of a metal catalyst and thus promoting the site-selective functionalization4. As the majority of the state-of-the-art reactions are compatible with only a few well-designed directing groups, a particular directing group often needs to be installed on a substrate of interest before the C–H activation step and removed after the functionalization event, significantly reducing the synthetic usefulness of the strategy and rendering it poorly compatible with the drug-development process. The collaboration between AstraZeneca (Johansson) and Ackermann at the University of Göttingen aims to overcome the serious limitation of directing groups, rendering this still rather academic field of C–H activation truly appealing for pharmaceutical research and development.

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Fig. 1: Late-stage methylation for medicinal chemistry.

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  1. Twitter: @DelordWencel

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  1. Laboratoire d’Innovation Moléculaire et Applications (UMR CNRS 7042), Université de Strasbourg/Université de Haute Alsace, Strasbourg, France

    Joanna Wencel-Delord

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  1. Joanna Wencel-Delord
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Correspondence to Joanna Wencel-Delord.

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Wencel-Delord, J. Decorating and diversifying drugs. Nat. Chem. 12, 505–506 (2020). https://doi.org/10.1038/s41557-020-0479-3

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  • C–H activation

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