Review Article | Published:

Towards the generalized iterative synthesis of small molecules

Nature Reviews Chemistry volume 2, Article number: 0115 (2018) | Download Citation

  • An Erratum to this article was published on 07 March 2018

Abstract

Small molecules have extensive untapped potential to benefit society, but access to this potential is too often restricted by limitations inherent to the highly customized approach that is currently used to synthesize this class of chemical matter. An alternative ‘building block approach’ — that is, generalized iterative assembly of interchangeable parts — has now proved to be a highly efficient and flexible method of constructing things ranging from skyscrapers and macromolecules to artificial intelligence algorithms. The structural redundancy found in many small molecules suggests that they possess a similar capacity for generalized building block-based construction. It is also encouraging that many customized iterative synthesis methods have been developed that already improve access to specific classes of small molecules. There has also been substantial recent progress towards the iterative assembly of many different types of small molecules, including complex natural products, pharmaceuticals, biological probes and materials, using common building blocks and coupling chemistry. Collectively, these advances suggest that a generalized building block approach for small-molecule synthesis may be within reach.

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Change history

  • Corrected online 07 March 2018

    In the version of this Article originally published, the author affiliations were incorrect. This error has now been corrected.

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Acknowledgements

J.W.L. is funded by NSF grant NSF CHE 15–66071, D.J.B. is supported by the Damon Runyon Cancer Research Foundation (Damon Runyon) postdoctoral fellowship and M.D.B. is supported by the US Department of Health & Human Services NIH grant R35GM118185.

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Affiliations

  1. Department of Chemistry, University of Illinois at Urbana-Champaign, 454 Roger Adams Laboratory, Urbana, IL, USA.

    • Jonathan W. Lehmann
    • , Daniel J. Blair
    •  & Martin D. Burke
  2. Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

    • Martin D. Burke
  3. Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

    • Martin D. Burke

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Contributions

All authors contributed equally to the preparation of this manuscript.

Competing interests

The University of Illinois has filed patent applications on MIDA boronate chemistry and the automated synthesis platform described herein. These inventions have been licensed to REVOLUTION Medicines, a company for which M.D.B. is a founder.

Corresponding author

Correspondence to Martin D. Burke.

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https://doi.org/10.1038/s41570-018-0115