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DOI: 10.1055/a-2464-7068
Synthesis the C1–C15 Fragment of Incednine
This work has been funded by the Agence Nationale de la Recherche (ANR) (SynTense ANR-21-CE07-0041-02), the Centre National de la Recherche Scientifique (CNRS), and the Université Paris Cité.
Abstract
We report on our progress towards the synthesis of the exotic, delicate, and tense polyketidic macrolactam of incednine. This work constitutes a significant advancement towards the total synthesis of a family of molecules of biological and medicinal interest. Some of the key features of this synthesis required evolutions from the initially designed strategy, leading to the use of a Horner–Wadsworth–Emmons olefination to build the C2–C9 tetraene. For this purpose, a polyfunctionalized phosphonate was used that was obtained through an unprecedented Pd-catalyzed cross-coupling involving the zinc salt of diethyl methylphosphonate. The resulting desired C1–C15 fragment displays a carboxylic acid ester at C1 and a vinyl iodide at C15, both functions being ready for subsequent amide coupling with the C16–C23 fragment and final Suzuki cyclization, respectively.
Key words
total synthesis - natural products - palladium - enantioselectivity - olefination reactionSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2464-7068.
- Supporting Information
Publication History
Received: 11 October 2024
Accepted after revision: 08 November 2024
Accepted Manuscript online:
08 November 2024
Article published online:
17 December 2024
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