Journal article
Collective asymmetric synthesis of the Strychnos alkaloids via thiophene S,S-dioxide cycloadditions
- Abstract:
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The Strychnos alkaloids have long been regarded as landmark targets for chemical synthesis due to their captivating architectures and notorious biological properties. However, the design of approaches that access multiple family members in an asymmetric, concise, and atom economical fashion remains a significant challenge. Here we show that thiophene S,S-dioxides (TDOs) offer a modular, rapid entry to the Strychnos natural products via inverse electron demand Diels-Alder cascades. Exceptional levels of stereocontrol are demonstrated in asymmetric TDO cycloadditions, which afforded tricyclic indolines of utility in medicinal chemistry research, and enabled stereoselective syntheses of eight Strychnos alkaloids by the shortest routes described to date, including the first synthesis of the iconic family member brucine. Using a machine-learning approach, computational studies provide insight into the source of stereoinduction, and reveal an intriguing and unexpected spontaneous cheletropic extrusion of SO2.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.0MB, Terms of use)
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- Publisher copy:
- 10.1038/s41557-025-02041-1
Authors
- Funder identifier:
- https://ror.org/0439y7842
- Grant:
- EP/X028674/1
- Publisher:
- Springer Nature
- Journal:
- Nature Chemistry More from this journal
- Volume:
- 18
- Issue:
- 4
- Pages:
- 782-789
- Publication date:
- 2026-01-23
- Acceptance date:
- 2025-12-02
- DOI:
- EISSN:
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1755-4349
- ISSN:
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1755-4330
- Language:
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English
- Keywords:
- Pubs id:
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2345767
- Local pid:
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pubs:2345767
- Deposit date:
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2025-12-05
- ARK identifier:
Terms of use
- Copyright holder:
- Park et al.
- Copyright date:
- 2026
- Rights statement:
- Copyright © 2026, The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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