Towards the generalized iterative synthesis of small molecules

Jonathan W. Lehmann, Daniel J. Blair, Martin D. Burke

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Article number0115
JournalNature Reviews Chemistry
Issue number2
StatePublished - 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)


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