Institut de Chimie des Substances Naturelles

Essential oils (EOs) from combined plant materials offer a promising alternative to conventional extraction by enhancing chemical diversity and bioactivity. This study evaluated the chemical composition and insecticidal properties of individual and combined plant EOs from Cymbopogon citratus, Eucalyptus camaldulensis, Eucalyptus lehmannii, Salvia rosmarinus and Thymus vulgaris were evaluated against aphids. Binary and ternary combinations were prepared in equal proportions prior to hydrodistillation. GC-MS analysis revealed significant compositional shifts in EOs from combined plant materials. Major compounds in individual oils included citral (53.11%) and neral (29.14%) in C. citratus, thymol (70.84%) in T. vulgaris, and eucalyptol as the predominant compound in E. camaldulensis (66.51%), E. lehmannii (56.99%) and S. rosmarinus (46.56%), respectively. In the combined oils, the relative abundance of these constituents was altered, and in some cases new constituents were introduced. Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) revealed that combined plant EOs clustered near their parental oils, indicating compositional inheritance. Contact toxicity assay against Aphis fabae demonstrated enhanced efficacy of the combined oils, with reduced LC50 values (1.39 µL mL-1 for E. camaldulensis + T. vulgaris) and synergistic interactions, indicated by a co-toxicity coefficient (CTC) of 221.58 and elevated synergistic factors. Pearson correlation analysis and Partial Least Squares (PLS) regression jointly identified Acorenone B and thymol as negatively, and caryophyllene as positively correlated compounds, all with relatively high contribution to insecticidal activity, ranking highest with a Variable Importance in Projection (VIP) scores > 1.0. While PLS model had modest predictive power, the integration of these statistical approaches supports the insecticidal potential of combined plant-derived EOS in laboratory bioassays and indicates their relevance to sustainable crop protection.

Seven-membered oxygen heterocycles, particularly Δ3-oxepenes, are prevalent motives, found, for example, in natural products, but remain synthetically challenging due to ring strain and limited asymmetric methods. Here, we describe a new strategy that uses Brønsted acid-promoted skeletal editing to convert enantioenriched dihydro-1,2-oxazinesreadily prepared via an enantioselective catalytic nitroso-Diels-Alder reactioninto highly substituted Δ3-oxepenes bearing four diastereo-controlled stereocenters. As supported by DFT studies, which also provide insight into the origin of the diastereoselectivity, the transformation proceeds via a transient aziridine intermediate and a regioselective nucleophilic ring-opening, enabling the incorporation of diverse nucleophiles, including thiols, alcohols, and indoles. Operating under mild conditions, this methodology delivers tetrasubstituted Δ3-oxepenes in decent yields and excellent enantiomeric excesses.

Open-shell intermediates have become central to modern organic synthesis, placing photoredox catalysis, and therefore the development of photocatalysts, as a crucial area of research. We report the development of a photocatalytic platform based on triaryl-heptazines, which possess a high level of tunability and high potency for oxidation reactions. A representative set of four photocatalysts from this family were synthesized and fully characterized (UV–vis absorption and emission spectroscopy, cyclic voltammetry, and time-correlated single-photon counting) showing high excited-state reduction potentials and long excited-state lifetimes. DFT and time-dependent DFT studies were performed and account for the observed photochemical properties. One of these photocatalysts was then used for oxidative transformations of nitrogen-containing molecules, namely, N-methyl oxidation to N-formyl compounds and C–C bond cleavage of cyclic N-protected amines. In both cases, this triaryl-heptazine catalyst displays synthetically significant features, notably in terms of selectivity and substrate scope. Moreover, mechanistic investigations provided valuable insights into the behavior of this photocatalyst in the reaction.

Covering up to 2025Natural products (NPs) from the terrestrial biodiversity play a key role in oncology drug discovery. While historically identified through bioactivity-guided fractionation, recent advances in high-content screening (HCS) assays, metabolomics, and in silico modeling have significantly enhanced the potential and attractiveness of flora-derived NPs for the development of anticancer therapeutics. This includes immunomodulatory molecules that are able to target the tumor microenvironment to promote immune-mediated clearance of the tumor, thereby improving patient response. This review highlights the untapped potential of molecules extracted from the South Pacific's terrestrial flora in the search for novel antitumor and immunomodulatory compounds. The unique biodiversity of Oceania, including Australia, New Zealand, and Pacific Island Countries and Territories (PICTs) across Micronesia, Melanesia and Polynesia, offers a promising yet largely unexplored reservoir for discovering plant-derived molecules with antitumor and immunomodulatory activities. Herein, we examine the recent pharmacological advances in this field and highlight the need for sustainable and collaborative research. Leveraging cutting-edge technologies could help overcome the challenge of NP-based drug discovery on these geographically isolated islands, unlocking the region's vast potential for plant-derived cancer therapeutics.

The Front Cover provides Chemistry Methods readers with a glimpse into the decision-making process that takes place during a mass spectrometry-driven natural products discovery workflow. To address this challenge, M. A. Beniddir and co-workers developed MS2DECIDE, a Python library that applies decision theory and expert knowledge to integrate the outputs of three widely used annotation tools–GNPS, SIRIUS, and ISDB-LOTUS–and generate recommendations for prioritizing natural products according to their potential novelty. For more details, see Research Article (DOI: 10.1002/cmtd.202400088).

BackgroundRapid and efficient epithelial regeneration is fundamental for tissue homeostasis and proper function. As the outermost ocular structure, the cornea is transparent, multilayered, and vital for clear vision. Due to its exposed position, the cornea frequently undergoes various forms of injury affecting either the epithelium itself or its surrounding microenvironment, including corneal innervation and the tear film. Corneal abrasion, occurring commonly through trauma or as part of refractive surgical procedures, is typically viewed as a minor event since it usually resolves rapidly. Consequently, the cornea serves as an excellent model for studying epithelial wound healing. However, complications such as persistent epithelial defects or corneal opacity can develop, underscoring critical gaps in understanding the underlying molecular mechanisms.MethodsUtilizing a unilateral corneal abrasion mouse model, we conducted a comprehensive multi-omics analysis, integrating transcriptomics, proteomics, and epitranscriptomics, to dissect the dynamic molecular responses post-injury in both wounded and contralateral tissues. To elucidate the role of the tear film, we performed additional studies involving lacrimal gland ablation combined with corneal injury. We applied RNA sequencing to profile transcriptomic changes in corneal and lacrimal gland tissues, and mass spectrometry to study tear proteomics and epitranscriptomic modifications.ResultsWe revealed a major modulation of the cornea transcriptome after abrasion, suggesting a regulation of pathways including JAK-STAT, Wnt and TGF-β, and a reduction of nucleoside modifications. The lacrimal gland transcriptome and tears proteome were also significantly affected. Plus, we highlighted a bilateralization, both in the cornea transcriptome and tears proteome. In the tear-deficient conditions, the wound closure rate and molecular responses were altered, and the bilateralization was impacted, with an increased matrix remodeling and a modulation of keratins expression.ConclusionsOur multi-omics analyses revealed extensive epithelial cellular plasticity as a key mechanism driving rapid wound closure, characterized by profound remodeling of transcriptional networks and RNA modifications. Importantly, we uncovered a previously underappreciated role of the lacrimal gland and tear film in mediating bilateral molecular responses following unilateral injury, emphasizing their pivotal roles in tissue regeneration. Additionally, we identified novel regulatory roles for RNA methylation events and critical signaling pathways implicated in epithelial healing.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s11658-025-00804-9.

We present a photocatalyst-free,visible-light-mediatedTruce–Smilesrearrangement (TSR) for the selective difunctionalization of olefinsby exploiting photoactivatable arylazo sulfones as sulfonyl radicalprecursors. This method efficiently affords β-sulfonyl-α-arylpropamidesin high yields with excellent stereoselectivity. Furthermore, by incorporatinga readily available chiral amino acid auxiliary (α-tert-butyl-leucine), we successfully developed a stereoselective variantof the TSR reaction, delivering optically enriched α-arylpropamideswith excellent diastereoselectivity (up to 20:1 dr). DFT calculationsprovided detailed insight into the key factors governing reactivityand selectivity, particularly the contrasting behaviors of N-alkyl and N-aryl acrylamides. Overall,this work provides a sustainable and practical method for constructingsulfonylated aryl compounds under mild and catalyst-free conditions.