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Peer-reviewedCC BYJournal of the American Chemical Society

Strategic Applications of Single-Atom Skeletal Editing in Natural Product Synthesis

  • Reem Al-Ahmad1
  • Isabel de la Torre Roehl2
  • Chang Liu1
  • Richmond Sarpong2
  • Mingji Dai1
  1. 1Emory University , , , ,
  2. 2University of California , , , ,
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Abstract

Skeletal editing is rapidly reshaping synthetic chemistry by enabling precise, atom-level modifications to complex molecular frameworks. Despite recent advances in methodology development, skeletal editing has yet to realize its full impact on complex molecule synthesis. In this Perspective, we highlight the power of single-atom skeletal editing transformations in enabling efficient syntheses of various complex natural products and advocate for the development of new methods and novel applications. We present guidelines rooted in historical precedent along with modern case studies that highlight when skeletal edits enable efficient synthesis, and where reactivity gaps still limit broader adoption. By analyzing the existing literature, we aim to inspire novel retrosynthetic disconnections, and steer new method development, which, collectively, will advance the fields of total synthesis and skeletal editing.

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Cite

BibTeXRIS
BibTeX
@article{alahmad2026strategic,
  title = {{Strategic Applications of Single-Atom Skeletal Editing in Natural Product Synthesis}},
  author = {Reem Al-Ahmad and Isabel de la Torre Roehl and Chang Liu and Richmond Sarpong and Mingji Dai},
  journal = {Journal of the American Chemical Society},
  year = {2026},
  month = may,
  doi = {10.1021/jacs.6c04423},
  url = {https://doi.org/10.1021/jacs.6c04423},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Strategic Applications of Single-Atom Skeletal Editing in Natural Product Synthesis
AU  - Reem Al-Ahmad
AU  - Isabel de la Torre Roehl
AU  - Chang Liu
AU  - Richmond Sarpong
AU  - Mingji Dai
PY  - 2026
DA  - 2026/05/22
JO  - Journal of the American Chemical Society
DO  - 10.1021/jacs.6c04423
UR  - https://doi.org/10.1021/jacs.6c04423
AB  - Skeletal editing is rapidly reshaping synthetic chemistry by enabling precise, atom-level modifications to complex molecular frameworks. Despite recent advances in methodology development, skeletal editing has yet to realize its full impact on complex molecule synthesis. In this Perspective, we highlight the power of single-atom skeletal editing transformations in enabling efficient syntheses of various complex natural products and advocate for the development of new methods and novel applications. We present guidelines rooted in historical precedent along with modern case studies that highlight when skeletal edits enable efficient synthesis, and where reactivity gaps still limit broader adoption. By analyzing the existing literature, we aim to inspire novel retrosynthetic disconnections, and steer new method development, which, collectively, will advance the fields of total synthesis and skeletal editing.
SN  - 0002-7863
SN  - 1520-5126
SN  - 1943-2984
ER  -