Poster De Conférence Année : 2025

Bio-Inspired Total Synthesis of Daphnepapytone A

Joan Pereira
  • Fonction : Auteur
  • PersonId : 1382644
Gilles Frison
Bastien Nay

Résumé

Daphnepapytones are sesquiterpene natural products isolated from the stems of Daphne papyracea in 2022, a plant utilized in traditional Chinese medicine against diabetes, rheumatic pain, and traumatic injury.[1],[2] The exploration of these constituents has been delayed by limited biomass availability, and their total synthesis has emerged as an attractive objective for additional studies. In this presentation, we will disclose the first total synthesis of daphnepapytone A, a tetracyclic structure incorporating a unique, highly substituted cyclobutane ring. Our retrosynthetic approach is partly biomimetic and involves a two-phase sequence: skeleton construction followed by late-stage oxidation. The key steps include an Eschenmoser–Tanabe fragmentation of (R)-carvone epoxide to generate a suitable aldehyde, which undergoes an allenylation, followed by a regioselective distal allenic Pauson–Khand reaction to construct the guaiane core. Then, oleodaphnone intermediate was engaged in a [2+2] photocycloaddition, affording the bridged cyclobutane core of the target molecule. Finally, a late-stage, chemoselective C–H oxidation yielded a triketone intermediate, which was reduced in a remarkably chemo- and stereoselective manner to deliver the natural product. During the course of this work, we observed unexpected rearrangements of the bridged core. In addition to the first total synthesis of daphnepapytone A, we achieved the first total syntheses of three other guaiane-type sesquiterpenes: oleodaphnone, diarthroncha C, and daphnenicillata W.

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Dates et versions

hal-05119189 , version 1 (18-06-2025)

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  • HAL Id : hal-05119189 , version 1

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Joan Pereira, Nicolas Casaretto, Gilles Frison, Bastien Nay. Bio-Inspired Total Synthesis of Daphnepapytone A. Rencontres de Chimie Organique XXI, Jun 2025, Versailles, France. ⟨hal-05119189⟩
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