Site-selective reactions are important tools in the synthesis of useful multisubstituted compounds, including pharmaceuticals and functional molecules. Such reactions convert functional groups in a selective manner, thereby enabling the synthesis of various compounds with different substitution patterns from a single starting compound. Although a number of transition metal-catalyzed site-selective reactions have been developed, site-selectivity is usually controlled by the substrate, limiting the scope of the reaction. In contrast, catalyst-controlled site-selective reactions of single substrates have been reported, wherein ligand-controlled reactions are of particular interest. Previously, our group developed hydroxyterphenylphosphine ligands to achieve the palladium-catalyzed ortho-selective cross-coupling reactions of dihalogenated phenols/anilines. In this system, the hydroxy groups of the ligand bind to the substrate via the metal, and the proximity of palladium to the halogen at the ortho-position accelerates the reaction at this less reactive position. These reactions have been employed to synthesize multisubstituted benzofurans and indoles from dichlorophenols/anilines using a one-pot ortho-selective Sonogashira coupling/cyclization/Suzuki–Miyaura coupling protocol. The developed catalyst also has enabled the direct C3-selective arylation of N-nonsubstituted indoles, and both tricyclic pyrroloindolines and pyridoindolines have been obtained from tryptamine derivatives via a C3-dearomative arylation/cyclization strategy. Furthermore, the site-selective arylation of N-nonsubstituted 1H-pyrroles has been achieved by changing the ligand, and the reaction proceeded selectively at the C2 or C3 position, yielding 2,2,5-trisubstituted 2H-pyrroles and other compounds whose preparation is challenging via conventional approaches. Finally, the regioselective synthesis of polycyclic aromatic compounds using appropriate palladium catalysts has been performed using the site-selective approach.

Ziziphi Fructus (the fruit of Ziziphus jujuba Miller var. inermis Rehder; Japanese name “Taiso”), listed in the 18th edition of the Japanese Pharmacopoeia (JP18), is widely used in Kampo (Japanese traditional) medicine. However, a specific identification test for Ziziphi Fructus was not prescribed in JP18. Hence, in this study, we establish a TLC-based identification test for quality assurance of the crude drug Ziziphi Fructus. The HPLC experiments identified 3-O-cis-p-coumaroylalphitolic acid and 3-O-trans-p-coumaroylaliphitolic acid as suitable indicators. After developing the samples to a distance of 10 cm using ethyl acetate (EtOAc)/n-hexane/acetic acid (AcOH)/H₂O (60 : 40 : 2 : 1) as the TLC-developing solvent and UV light at 254 nm, two spots with an Rf value of approximately 0.4–0.6 were detected. Additionally, based on the TLC-based experiments, alphitolic and maslinic acids emerged as potential indicator components. Treatment of samples with EtOAc/n-hexane/AcOH (60 : 40 : 1) serving as the developing solvent, followed by exposure to dilute sulfuric acid solution, heat, and UV light at 365 nm, revealed two clear spots with Rf values of approximately 0.2–0.3. These findings potentially serve as a basis for the development of an identification test to identify Ziziphi Fructus.

Bicyclo[1.1.0]butane (BCB) is a highly strained compound with unique reactivity. In this work, we discovered that a BCB derivative bearing an aryl and a diisopropylamide group undergoes an oxygen-mediated transformation to give the corresponding oxazolidin-4-one derivative in good yield under mild conditions (EtOAc, O₂, 40 °C). The structure of the product was confirmed by X-ray crystallographic analysis, and radical trapping experiments suggested that the reaction involves a radical pathway. This reaction enables direct conversion of BCB carbon atoms into a heterocyclic scaffold with a high atom economy.

The Hippo signaling pathway plays a central role in regulating cell growth, and dysregulation of its downstream effector Yes-associated protein (YAP) leads to tumorigenesis. Verteporfin (VP), a clinically approved drug, inhibits YAP–TEA domain (TEAD) complex formation, yet its binding mechanism remains unclear. In this study, we conducted a comprehensive in silico analysis of all 4 VP isomers within the context of the full-length YAP–TEAD complex. The complex structure was modeled using AlphaFold2 multimer, which provided sufficient accuracy for docking simulations despite incomplete experimental data on YAP. Docking calculations were performed against 2 grids, one centered on a predicted druggable pocket and the other on the YAP–TEAD interface. A total of 304 poses were generated, and the top-scoring 100 were clustered using protein–ligand interaction fingerprints. Clusters derived from the interface grid revealed strong interactions with residues critical for YAP–TEAD binding. Among the 4 isomers, Ia-2 consistently showed the most favorable binding free energies. Notably, Cluster 7 highlighted a unique Ia-2 binding mode involving simultaneous interactions with Met86 and Arg87, suggesting a competitive mechanism at the YAP–TEAD interface. These results suggest that structural chirality may influence binding stability and interaction patterns, and that the Ia-2 isomer is predicted to preferentially stabilize an inhibitory binding mode. This study provides the first systematic comparison of all VP isomers with full-length YAP and suggests that isolating Ia-2 from Visudyne may enhance anticancer efficacy. The findings further support the rational strategies for designing selective YAP–TEAD inhibitors.

Pseudocyclic arylbenziodoxaboroles are unique aryne precursors under neutral aqueous conditions that selectively react with tertiary organic phosphines or amines at room temperature to form the corresponding aryl-substituted quaternary phosphonium or ammonium salts in high yields. This reaction has been further extended to the preparation of tetraarylarsonium and tetraarylstibonium salts.

A new depsidone, termed mollicellin Z2 (1), and three known mollicellins D, H, and I (2–4), were isolated from cultured Chaetomium brasiliense NBRC 6548 mycelia. The structure of 1 was determined from one dimensional (1D) and 2D-NMR and high resolution electron ionization (HREI)MS spectra. It is the first 4-desmethyl mollicellin analogue found to contain a C-7 prenyl group and is likely generated via a biosynthetic pathway that is distinct from those that produce the 27 known analogues. This is the first report of mollicellin derivatives with antibacterial activity against nontuberculous mycobacteria.

The clinical application of natural core streptavidin remains unrealized owing to its immunogenicity and interference from endogenous D-biotin. These limitations could be addressed using D-core streptavidin, the mirror-image form. Here, we evaluated the immunogenicity and biodistribution of D-core streptavidin in mice. Intraperitoneal administration of natural core streptavidin induced antibodies against streptavidin, whereas no antibody production was observed for D-core streptavidin. The protease assay indicated that proteolysis by cathepsin B differed between D-core streptavidin and the natural core form. The difference in degradation by cathepsin B in non-denatured conditions may contribute to the reduced immunogenicity of D-core streptavidin. Biodistribution studies revealed no significant differences between D-core and natural core streptavidins in tumor-bearing mice. These findings support the further development of D-core streptavidin in combination with L-biotin for in vivo applications.

To achieve efficient transdermal delivery of rutin, a microemulsion (ME) system was developed by incorporating deep eutectic solvents (DES) as the inner phase and surface-active ionic liquids (SAILs) as surfactants. The DES used in this study is choline chloride/polyethylene glycol (PEG) 200, while the SAILs used were 1-alkyl-3-methylimidazolium bromides (Cn mimBr) with alkyl chain lengths of 10, 12, and 16 (C10 mimBr, C12 mimBr, C16 mimBr). Structural characterization by small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) showed that MEs incorporated with C10 and C12 mimBr formed a cylindrical structure, where C16 mimBr formed spherical structures. MEs containing C10 or C12 mimBr exhibited significantly higher skin permeability of rutin, approximately 6.8 times greater compared with conventional water-in-oil (W/O) MEs. These results suggested that SAIL-based MEs are one of the promising drug carriers in the transdermal delivery of rutin.

Alzheimer’s disease (AD) is a brain disorder associated with amyloid beta (Aβ) aggregation, leading to neuronal damage and faster disease progression. The aggregation-inhibiting compounds are necessary to prevent and treat AD. Acer species are rich in phenolic compounds and possess diverse biological activities. In this study, we investigated the Aβ₄₂ aggregation inhibitory activity of the understudied species, Acer amoenum var. matsumurae red and green leaf extracts, using thioflavin T and also monitored 24-h Aβ₄₂ aggregation kinetics. The red leaf extract showed the strongest inhibition (half-maximal effective concentration [EC₅₀] = 1.28 mg/mL), and the green leaf extract showed moderate inhibition (EC₅₀ = 8.61 mg/mL). In addition, the time-course profile of Aβ₄₂ aggregation at a concentration of 75 µg/mL was performed. The red leaf extract indicated strong inhibition in the Aβ₄₂ fibril formation when compared to the green leaf extract and was analyzed by fitting the experimental data to an empirical sigmoidal function (logistic function). The red leaf exhibited significantly stronger 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (IC₅₀ = 2.81 µg/mL) compared to the green leaf (IC₅₀ = 6.27 µg/mL). The red leaf extract exhibited greater monomeric anthocyanin content than the green leaf extract, as determined by the pH-differential method. The active compound was isolated and identified by using chromatographic and spectroscopic techniques. These results suggest that A. amoenum var. matsumurae red leaf extract and the active compound epicatechin may prove to be Aβ aggregation inhibitors to prevent or delay AD progression.