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Mix-and-match synthesis of 3D small molecules

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Why This Matters

The development of new methods for synthesizing C(sp3)–C(sp3) bonds with controlled 3D configurations marks a significant advancement in organic chemistry. This breakthrough enables more efficient creation of diverse small molecules, which can lead to innovative medicines, materials, and flavors, ultimately benefiting both the industry and consumers. By expanding the toolkit for modular molecule assembly, this research paves the way for more precise and versatile drug development and material design.

Key Takeaways

Small organic molecules underpin modern life, from medicines and flavours to advanced materials. Much of this functional diversity comes from shape: modest changes in a molecule’s 3D structure can completely change its properties. To explore these structural effects efficiently, chemists often synthesize libraries of compounds through the Lego-like assembly of molecules from interchangeable chemical building blocks1. However, such approaches are only as useful as the types of carbon–carbon (C–C) bond that form between the building blocks during assembly. Writing in Nature, Zhang et al.2 report chemistry that not only enables the modular and iterative synthesis of a ubiquitous type of C–C bond — C(sp3)–C(sp3) bonds, which connect carbons that are already attached to three other atoms — but that also controls the 3D configuration of the attached atoms.

Nature 652, 303-304 (2026)

doi: https://doi.org/10.1038/d41586-026-00809-0

References Lehmann, J. W., Blair, D. J. & Burke, M. D. Nature Rev. Chem. 2, 0115 (2018). Zhang, X., Palka, K. T., Zhang, M. & Morken, J. P. Nature 652, 359–364 (2026). Leitereg, T. J., Guadagni, D. G., Harris, J., Mon, T. R. & Teranishi, R. Nature 230, 455–456 (1971). Cherney, A. H., Kadunce, N. T. & Reisman, S. E. Chem. Rev. 115, 9587–9652 (2015). Choi, J. & Fu, G. C. Science 356, eaaf7230 (2017). Noguchi, H., Hojo, K. & Suginome, M. J. Am. Chem. Soc. 129, 758–759 (2007). Blair, D. J. et al. Nature 604, 92–97 (2022). Download references

Competing Interests D.J.B is listed as an inventor on patents relating to (tetramethyl N-methyliminodiacetic acid) (TIDA) boronates used in modular synthesis. Financial support to D.J.B. was provided by the National Institutes of Health R35GM159997.

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