The biosynthetic study of secondary metabolites in ectomycorrhizal mushrooms has been hindered by limited mycelial growth and transcriptional silencing of biosynthetic genes under artificial conditions. Ustalic acid, a Na⁺/K⁺-ATPase inhibitor and a common cause of mushroom poisoning in Japan, was originally identified in the fruiting body of Tricholoma kakishimeji and was thought to be absent in its mycelium. Here, we demonstrate for the first time the production of ustalic acid in the cultured mycelia of T. stans and T. albobrunneum, two species that were recently segregated from T. ustale by phylogenetic analyses. LC–MS profiling also detected polyporic acid and additional ions consistent with oxidized derivatives of polyporic acid but failed to identify phlebiarubrone, which was previously considered as the biosynthetic precursor of ustalic acid. Genome sequencing and bioinformatic analysis of the sequence information identified a candidate biosynthetic gene cluster for ustalic acid. This cluster was named the uta cluster, and heterologous expression of the uta genes in Aspergillus nidulans afforded polyporic acid, supporting its role in the scaffold assembly. While the downstream biosynthetic steps remain to be investigated, this work establishes the basis for future biochemical and genetic studies of ustalic acid biosynthesis.

The tablet is the most versatile dosage form in the pharmaceutical field due to its small size and excellent portability and ingestibility. Tablets are the most commonly used oral solid preparations, and are manufactured by compressing powders containing an active ingredient and excipients. In the manufacturing process, some materials from the tablet may adhere to the die wall, and tableting failures from damage due to binding may occur at the sides of the tablet. The definition and mechanisms of binding, the advantages of various assessment methods, and the current challenges and progress of assessment methods are comprehensively reviewed herein. Efforts to predict the risk of binding have been attempted using a multi-functional compaction instrument, tableting simulators, and simulations based on physicochemical parameters. Several analytical approaches have been applied as conventional evaluations for binding, such as visual observations of the tablet and die wall, measurements of ejection stress, differences between upper and lower punch forces, and die wall stress. However, these evaluation methods cannot always provide both qualitative and quantitative information and, thus, a more reliable evaluation strategy is desired. A newly-developed qualitative and quantitative evaluation method for powder adhesion to the die wall after tableting, named Binding Identification for Net Detriment (BIND), and its various applications to avoid binding are also reviewed herein. This review also focuses on the analytical performance and reliability of binding evaluations for commercial production.

In this study, waste basil seed (BS) was prepared and evaluated for the removal of methylene blue (MB) dye from aqueous media. BS was characterized using scanning electron microscopy, specific surface area, surface functional groups, and the point of zero charge (pH_pzc). Spherical particles were observed in virgin BS. The specific surface area and pH_pzc value were 0.265 m²/g and 5.59, respectively. In addition, acidic and basic surface functional groups were measured as 0.050 and 0.605 mmol/g, respectively. The MB adsorption study demonstrated that the adsorption capacity increased with increasing initial concentration (10–100 mg/L) and with decreasing temperature (45 –7°C). The pH of the MB solution significantly affected adsorption, with the highest uptake observed at the neutral and basic pH levels. The data fitted well to the Langmuir isotherm model and the pseudo-2nd-order model, with correlation coefficients of 0.899–0.993 and 0.996, respectively, under the tested conditions. Furthermore, elemental distribution analysis, binding energy evaluation, and adsorption capability revealed that MB adsorption on the BS surface was closely related to the cellulosic hydrocolloid components. Overall, BS exhibited a promising adsorption capacity and could serve as an effective material for MB removal from aqueous media.

We report here a synthesis of gem-difluorocyclopropanes via a copper-catalyzed C(sp³)–H addition of dioxolane to difluorocyclopropenes. The combinational use of silane and dibenzoyl peroxide was crucial for promoting the reaction, enabling access to gem-difluorocyclopropanes with an acetal moiety in a cis configuration.

Kakadu plum (Terminalia ferdinandiana) reportedly has the highest ascorbic acid levels of all plants worldwide and its juice reactivates functions of the retinoblastoma gene (RB) product, a tumor suppressor gene. In this study, the juice of the Kakadu plum was fractionated to identify the constituent active compounds. A novel ellagitannin, named terminalagin, was isolated from Kakadu plum (Terminalia ferdinandiana) juice via bioassay-guided isolation. The structure was determined using spectroscopic analysis and partial hydrolysis. Terminalagin has a corilagin substructure and a 2,4-(S)-hexahydroxydiphenoyl (HHDP) ester moiety that is not usually found in natural products. The results of this study enrich the structural database of ellagitannins and should provide invaluable aid for their further utilization in cancer prevention.

We designed and synthesized an oligonucleotide acetylating reagent (Ac-probe) that selectively acetylates the 2′-OH groups of RNA upon forming a duplex with the target RNA. The Ac-probe can be readily prepared via a post-synthetic modification method using an oligodeoxynucleotide probe containing 4-thio-dT. During the acetylation reaction, 4-thio-dT is regenerated as the reaction proceeds. Notably, an efficient modification was observed when the complementary base of RNA to 4-thio-dT was cytosine or uracil, indicating the selectivity for the pyrimidine base.

Site-selective conjugation on aryl azides is hampered by a fundamental trade-off: electron-withdrawing groups that promote the reaction often preclude further functionalization, while versatile electron-donating groups suppress reactivity. We report a strategy that resolves this by using an ortho-amido group to activate an electron-rich aryl azide via an intramolecular hydrogen bond. This non-covalent interaction renders the ortho-amidoaryl azide significantly more reactive than its para-isomer and even activated alkyl azides, although competition experiments revealed that steric hindrance presents a counteracting effect. The principle was successfully applied to achieve excellent site-selectivity in a diazide molecule, favoring reaction at the aryl position. Its utility was further demonstrated in a highly selective classical Staudinger–Bertozzi ligation. This work establishes the ortho-amido group as a powerful controlling element, offering a new click conjugation platform that enables ready functionalization.

Immunoglobulin G (IgG)-binding peptides have been widely used in medicinal chemistry, particularly in the preparation of homogeneous antibody–drug conjugates (ADCs). The dissociation constant (K_d) and kinetic parameters (k_on and k_off) are critical determinants of peptide performance in such applications. In this study, we conducted a structure–activity relationship (SAR) analysis of the IgG-binding peptide 15-IgBP, focusing on Asp3, Tyr6, and Thr15, to identify more potent derivatives with favorable binding affinities and kinetic profiles. Peptides with appropriately tuned ionic structures exhibited rapid binding and release properties, whereas hydrophobic substitutions in solvent-exposed regions led to slower dissociation. By integrating these SAR findings, we identified the optimized affinity peptides, IAPG-2 and IAPG-3, with sub-nanomolar binding affinities (K_d = 0.753 and 0.705 nM, respectively).

Ultra performance liquid chromatography (UPLC)-high resolution (HR)MS/MS and feature-based molecular networking analysis were performed for the extract of a fungus, Arachnomyces bostrychodes, obtained from a cold seep chemosynthetic ecosystem, revealing the presence of new peptides. LC-MS-guided purification afforded three new cyclic tetrapeptides (3–5) containing two N-methyl-l-leucine residues. During the isolation procedure, a new benzophenone (1) and MDN-0093 (2) were isolated. Compounds 4 and 5 exhibited cytotoxicity against HeLa cells with IC₅₀ values of 3.1 and 5.8 μM, respectively.

This study explored the degradation of water-soluble cannabidiol (CBD) products in surfactant-containing gastric fluid. It was hypothesized that various surfactants would catalyze CBD degradation, and their chemical properties were investigated in detail. CBD products (CBD oil and two water-soluble CBD products) were dissolved in water containing nine surfactants: C₈H₁₇SO₄Na, C₁₀H₂₁SO₄Na, C₁₂H₂₅SO₄Na (sodium dodecyl sulfate; SDS), C₁₄H₂₉SO₄Na, C₁₆H₃₃SO₄Na, C₁₂H₂₅SO₃Na, C₁₂H₂₅HPO₄Na, polysorbate 80, and benzethonium chloride. Simulated gastric fluid (SGF) was added to each sample, and reactions were performed at 37°C for 15–120 min. Concentrations of CBD and reaction products were analyzed using HPLC coupled with a photodiode array detector. The chromatographic analysis confirmed CBD degradation in the presence of surfactant catalysts such as C₁₄H₂₉SO₄Na, SDS, C₁₂H₂₅SO₃Na, C₁₆H₃₃SO₄Na, and C₁₂H₂₅HPO₄Na (listed in the ascending order of conversion rates). Conversely, no CBD degradation occurred in certain reaction mixtures in SGF. Specifically, other cannabinoids were not detected in samples containing CBD oil with SDS or water-soluble CBD products with C₈H₁₇SO₄Na and C₁₀H₂₁SO₄Na surfactants. Similarly, no conversion was observed with cationic/nonionic surfactants or without surfactants. This study first demonstrated the degradation of CBD in gastric fluid containing surfactants other than SDS. This conversion occurs only when CBD is formulated in water-soluble products. The anionic surfactants soluble in SGF were the most effective surfactant catalysts. While future in vivo studies are necessary, these findings suggest that co-administration of CBD products with anionic surfactants disturbs the dose adjustment of CBD that exhibits high inter-/intra-individual variability and produces other cannabinoids.

We report a practical approach for synthesizing a chiral building block en route to the asymmetric total synthesis of dragmacidin E. The strategy features a base-promoted olefin isomerization of 1 followed by an Ir-catalyzed asymmetric hydrogenation under ambient hydrogen pressure. Gram-scale hydrogenation of geminally di-substituted olefin 5 using 3 mol% of the chiral Ir catalyst (R,R)-2 afforded (+)-(R)-3 in 88% yield and 89% enantiomeric excess (ee).