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. 2022 Jan 10;13:39. doi: 10.1038/s41467-021-27804-5

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© The Author(s) 2022

Open Access 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a General categorization of prodrug types can be made via their activation pathway, which are either naturally- or externally-triggered. This study aims to develop a working example of a synthetic prodrug. b Retrosynthetic prodrug design is a concept that aims to design prodrugs that transform into bioactive molecules via a bond-forming reaction. The proposed synthetic prodrug design relies on a sequential RCM/aromatization reaction to construct phenyl-containing bioactive agents.