The genus Ocotea is a significant source of bioactive agents within the Lauraceae, yet it remains underexplored. Despite its ethnomedicinal relevance and chemical diversity, Ocotea species remain taxonomically challenging as they belong to the multifaceted "Ocotea complex", a phylogenetically unresolved group. Moving beyond previous literature Ocotea surveys, this review provides the first curated, genus-specific data set of both volatile and nonvolatile specialized metabolites. Covering research articles from 1830 to 2025, this review provides the most comprehensive synthesis to date, documenting 984 unique chemical compounds across 115 species. This effort culminated in the construction of the Ocotea Chemical Database (OcoteaDB), a novel digital resource created to streamline the genus's chemical diversity for the global scientific community. Furthermore, it presents current knowledge of biosynthetic routes leading to key bioactive scaffolds, including aporphinoid and benzylisoquinoline alkaloids, lignoids, glycosylated flavonoids, and a diverse array of terpenoids, while addressing the stereochemical and structural intricacies unique to the genus. This review lays a robust foundation to drive future Ocotea-focused bioprospecting studies and guides research in the fields of natural products, chemophenetics, metabolomics, and medicinal chemistry regarding the Ocotea species, its chemical scaffolds, and specialized metabolites.

Nine undescribed polyheterocyclic pyrrole alkaloids, pseudoheterines A-I (1-7, 11, and 12), along with four known analogues (8-10 and 13), were isolated from the plant Pseudostellaria heterophylla. The structures and absolute configurations of compounds 1-7, 11, and 12 were determined by extensive spectroscopic analysis, ECD calculations, and X-ray diffraction. Compounds 1-6 are six unprecedented tetracyclic alkaloids with a triheterocyclic moiety, pyrrole-dihydrofuran-pyrrolidone core. Compounds 1, 3, and 5 present a fourth aromatic heterocyclic ring D, while 2, 4, and 6 possess an aromatic ring attached by an ester linkage. Compounds 6 and 9 exhibited neuroprotective activities by inhibiting apoptosis in CdCl2-induced PC-12 cells, and ameliorated CdCl2-induced neural damage in zebrafish.

Linear long-chain hydrocarbons are common constituents of the outer cuticle of most insects. These cuticular hydrocarbons form the first barrier to the environment, preventing desiccation, but also play important roles in communication among many insects, transporting, for example, information on species, sex, or physiological state. Eueides is a genus of heliconiine butterflies, a group known for their complex mimicry systems. We report here the identification and synthesis of large macrocyclic lactones from the cuticles of five Eueides species, which largely replace the hydrocarbons. These lactones have chain lengths of 23-34 and ring sizes of 17-29. They occur in Eueides but not in other closely related genera such as Heliconius, Dryas, Dryadula, Agraulis, or Dione. Each species has a specific mixture of macrocyclic lactones. These unique bouquets may be used in species recognition, as visual cues may be unreliable in mimicry rings. We identified 43 different compounds using GC/MS, GC/IR, and enantioselective synthesis via ring-closing metathesis and Jacobsen hydrolytic kinetic resolution. The absolute configuration could not be determined because these lactones were not separable by gas chromatography on chiral phases.

Tetrodotoxin (TTX) is a potent neurotoxin widely distributed among marine and terrestrial animals, yet how terrestrial vertebrates acquire this toxin has been debated for decades. Here, we identify oribatid mites as the primary dietary sources of TTX for the Japanese fire-bellied newt, Cynops pyrrhogaster. We detect TTX and its analogs in the mites Scheloribates processus and Galumna sp. KM1, which are preferentially consumed by terrestrial newts. In a controlled toxification experiment, juvenile newts accumulated TTX after consuming TTX-bearing mites, directly demonstrating dietary acquisition. Our results support that the early terrestrial stage is critical for lifelong TTX acquisition in the C. pyrrhogaster. Notably, we also detect pumiliotoxin, a poison-frog alkaloid, in S. processus, suggesting that newts and poison frogs have convergently evolved to exploit toxin-bearing microarthropods for chemical defense. We propose a "terrestrial toxic web" hypothesis in which oribatid mites act as a shared environmental reservoir linking putative microbial toxin production to vertebrate chemical defense, highlighting microarthropods as potential key mediators in terrestrial toxin flow.

Four previously undescribed polyketides, spiroeutypetides A-B (1-2), eutypetide I (3), and eutypetide J (4), were isolated from the rice culture of the marine-derived fungus Eutypella sp. F0219. Of these, compounds 1-3 possess unprecedented carbon skeletons, whereas 4 is a new polycyclic 10-membered lactone. The structures, including absolute configurations, were elucidated via spectroscopic data analysis, modified Mosher's method, X-ray crystallography, GIAO 13C NMR (DP4+) calculations, and ECD calculations. Spiroeutypetides A (1) and B (2) are two novel C16 polyketides featuring distinct spirocyclization patterns, forming 5/6/5 and 6/6/5 tricyclic systems, respectively, whereas eutypetide I (3) is the first C16 polyketide characterized by cleavage of the C4-C5 bond. All compounds were evaluated for their inhibitory effects on NO production in lipopolysaccharide-activated BV2 microglial cells. Eutypetide J (4) exhibited significant antineuroinflammatory activity by inhibiting microglial polarization and suppressing inflammasome-related proteins, including NLRP3 and caspase 1.

The defining feature of calcium-dependent antibiotics (CDAs) is that they require the presence of calcium cation (Ca(II)) as a cofactor to exert antibacterial activity. We recently showed that substituting two key aspartic acids (Asp) with serine (Ser) in laspartomycin C (LspC) converts it from a CDA into a boron-dependent antibiotic (BDA). This synthetic analog (termed B1) no longer depends on Ca(II) and requires only 10 μM of phenylboronic acid (PBA) to become fully active. Such a calcium-to-boron dependence conversion provides a new entry point to study the mechanistic details of the cofactor dependence of CDAs, a rare phenomenon among bioactive small molecules. Herein, we show that electron withdrawing substituents on PBA enhance the antibacterial activity of B1. The friulimicin and daptomycin synthetic analogs with the same Asp-to-Ser substitution were inactive, whereas the CDA4b synthetic analog exhibited dual cofactor dependence. CDA4b was fully activated when both Ca(II) and PBA were present and was 4-fold less potent in the presence of only one or the other. These findings suggest that not only do CDAs often have distinct cellular targets, the way they are activated by Ca(II) are also different. Such mechanistic diversity underscores the strong potential of CDAs in drug development.

GATA-3 serves as a key transcription factor driving Th2 cell differentiation and allergic cytokine production. Identifying the natural modulators of GATA-3 could provide therapeutic opportunities for the regulation of allergic responses. This study aimed to identify Vitis amurensis-derived natural products with strong GATA-3 inhibition and to elucidate their binding modes and mechanisms of action. The DNA-binding domain 2 (DBD2) of human GATA-3 was analyzed by using NMR spectroscopy, including backbone assignment. Isolated natural compounds were screened for binding activity, followed by reporter gene assays to evaluate the transcriptional inhibition potential. Two-dimensional NMR and docking studies were conducted to characterize binding interactions and identify binding sites. Stilbenoids from V. amurensis showed specific binding to the DNA-binding domain of GATA-3, as detected by 2D NMR. Reporter gene assays revealed dose-dependent transcriptional inhibition by these compounds. One of the hit compounds, KUP149, exhibited two binding modes on DBD2 based on NMR data, both of which can disrupt GATA-3-DNA interactions. These findings suggest stilbene-based natural products as potential inhibitors of allergic immune responses via GATA-3 modulation.

We herein disclose that the epimerization of yahazunol can lead to an antifungal enhancement. Yahazunol-related drimane meroterpenoids and pseudonatural mimics were synthesized based on an improved synthesis of 9-epi-borono-sclareolide and the concomitant Suzuki coupling. Several 9-epi-drimane meroterpenoids presented antifungal activity. The new stereoisomer 9-epi-yahazunol (EC50 = 4.32 μM) and its analog S-T5 (EC50 = 2.8 μM) showed much better antifungal activity than yahazunol (EC50 >150 μM) against Rhizoctonia solani. Compound S-T5 possesses a promising in vivo efficacy against R. solani, with preventive efficacies of 87% and 71% at 100 and 50 μM, respectively. It not only induced wizened and wrinkled mycelia but also caused cell membrane damage or disruption in R. solani, as evidenced by a series of biochemical investigations. The biosafety assessment showed that S-T5 had no adverse effects on seed germination. Configuration inversion may be an alternative strategy for developing new potent antifungal mimics of drimane meroterpenoids.

Four new pyrazine derivatives, namely (S,E)-1-((5-(3-hydroxy-2-(hydroxymethyl)styryl)-3,6-dimethylpyrazin-2-yl)methyl)-1,3-dihydroisobenzofuran-4-ol (1), (S,E)-1-((5-(3-hydroxy-2-(methoxymethyl)styryl)-3,6-dimethylpyrazin-2-yl)methyl)-1,3-dihydroisobenzofuran-4-ol (2), (S,Z)-1-((5-(3-hydroxy-2-(methoxymethyl)styryl)-3,6-dimethylpyrazin-2-yl)methyl)-1,3-dihydroisobenzofuran-4-ol (3), and (S)-1-((5-(3-hydroxy-2-(methoxymethyl)phenethyl)-3,6-dimethylpyrazin-2-yl)methyl)-1,3-dihydroisobenzofuran-4-ol (4), together with one new 1,3-dihydroisobenzofuran derivative, (S)-2-(4-hydroxy-1,3-dihydroisobenzofuran-1-yl)acetamide (5), were isolated from the endophytic fungus Alternaria sp. HJT-Y7 collected from the leaves of Rhodiola tibetica. Their structures were determined based on extensive spectroscopic analysis and comparison of experimental and calculated electronic circular dichroism (ECD) curves. 1, 4, and 5 significantly inhibited osteoclast differentiation in RANKL-induced RAW264.7 cells and markedly restored bone mineralization in a dexamethasone-induced zebrafish osteoporosis model. These results highlight the potential of 1, 4, and 5 as promising candidates for osteoporosis therapy.