Chemical & pharmaceutical bulletin最新文献

A squaramide organocatalyst was employed to efficiently promote asymmetric oxidative lactonization to construct spiro-fused 2-oxindoles in moderate-to-good yield and enantioselectivity (up to 81% enantiomeric excess (ee)). Herein, we report the first study accomplishing stereoselective oxidative cyclization from indole propionic acid using an organocatalyst, N-iodosuccinimide (NIS), and hydrogen peroxide under metal-free and mild reaction conditions.

This study examined the potential of waste basil seeds (BSs) calcined at 500°C or 1000°C (BS500 or BS1000, respectively) for gadolinium removal from aqueous solutions. Gadolinium ion adsorption onto the produced adsorbents was also assessed in relation to a number of parameters, including initial concentration, adsorption temperature, exposure time, and pH. Higher initial concentrations, adsorption temperatures, and exposure times (BS, BS500 ≒ BS1000) resulted in an increase in the quantity of adsorbed gadolinium ions; To further understand the adsorption mechanism, detailed analyses of elemental distribution and binding energy were conducted. According to the proposed mechanism, gadolinium adsorption onto BS1000 may involve an ion exchange process, wherein hydrogen ions from functional groups such carboxyl and hydroxyl groups on the surface of BS1000 are replaced by gadolinium ions. Additionally, the effects of coexisting ions on gadolinium adsorption were investigated, revealing that while monovalent cations did not impact gadolinium ion adsorption capacity, divalent and trivalent cations significantly reduced it. Finally, the desorption of gadolinium ions was tested using desorption agents such as distilled water, hydrochloric acid, and sodium hydroxide. The results revealed that a 100 mmol/L hydrochloric acid solution was particularly effective for desorbing gadolinium ions. Overall, BS1000 demonstrates promising properties as an adsorbent for gadolinium ion removal from aqueous solutions.

We report the catalyst-free aminoalkylation of alkenes, enabled by the formation of an electron donor-acceptor (EDA) complex between alkenes and amine-tethered N-hydroxyphthalimide (NHPI) esters. This visible-light induced transformation proceeds without external photocatalysts or additives. Spectroscopic and computational analyses support EDA complex formation, which undergoes photoinduced single-electron transfer to generate a radical ion pair that initiates C-N bond formation via intramolecular cyclization. The reaction exhibits a broad substrate scope, including electron-rich and electron-deficient alkenes, as well as structurally diverse NHPI esters, enabling access to various nitrogen-containing heterocycles such as pyrrolidines, benzodioxoles, and furan-fused frameworks. This operationally simple and modular method is a valuable platform for constructing biologically relevant molecules under mild conditions.

Bisenarsan is an organoarsenic natural product identified from actinomycetes and a derivative of (2-hydroxyethyl)arsonic acid (2-HEA) esterified with 2,4,6-trimethyl-2-nonenoic acid (2,4,6-TMNA). Our previous study suggested that bisenarsan is biosynthesized from arsenate [As(V)] via arsonoacetaldehyde (AnAA). In contrast, the late-stage biosynthetic steps from AnAA to bisenarsan and the roles of transporter genes within the biosynthetic gene clusters (BGCs) of bisenarsan remain unclear. In this study, through in-frame deletions and heterologous expression targeting the bisenarsan BGC in Streptomyces lividans 1326 (bsn cluster), we identified bsnF (nicotinamide adenine dinucleotide phosphate-dependent oxidoreductase), bsnPKS (iterative type I polyketide synthase), and bsnFB (3-ketoacyl-acyl carrier protein synthase III family protein) as genes encoding enzymes likely responsible for the late-stage biosynthesis of bisenarsan. BsnF, BsnPKS, and BsnFB are presumed to catalyze the reduction of AnAA to 2-HEA, the formation of the 2,4,6-TMNA moiety, and the ester bond formation, respectively. Furthermore, based on the functional analysis of the transporter genes in the bsn cluster, BsnT2 (major facilitator superfamily transporter) appears to be involved in the efflux of bisenarsan. Although the roles of other transporters in bisenarsan biosynthesis remain unclear, they may contribute to the uptake and efflux of inorganic arsenic, presumably to ensure a consistent substrate supply and mitigate toxicity caused by its overaccumulation. Our study provides valuable insights into the biosynthesis of a rare class of organoarsenic natural products, with arsonopyruvate as an intermediate.

A concise gram-scale total synthesis of (±)-makaluvamine F was accomplished. The left segment, 2-aminodihydrobenzothiophene possessing an N,S-acetal moiety, was prepared using commercially available 2-fluoro-4-methoxybenzaldehyde in 6 steps via Curtius rearrangement. Subsequent condensation of the 2-aminodihydrobenzothiophene segment with a pyrroloiminoquinone segment completed the total synthesis of makaluvamine F, which was achieved in a 23% overall yield via a longest linear sequence of 7 steps. The versatility of the synthetic route involving the Curtius rearrangement was demonstrated by applying it to synthesize several unnatural makaluvamine F derivatives.

Here, a DNA cleavage reagent (1-(anthracen-9-ylmethyl)-1,5,9-triazacyclododecane = Ant-[12]aneN3) was designed and synthesized, and its DNA photocleavage activity under UV irradiation at λ = 365 nm was evaluated. Ant-[12]aneN3 is a molecule containing anthracene as the photosensitizer and [12]aneN3 ( = 1,5,9-triazacyclododecane) as the DNA-interacting component. The cyclic polyamine [12]aneN3 could coordinate with zinc ions (Zn^II) and affect DNA cleavage activity. Therefore, when Ant-[12]aneN3 reacted with Zn(NO₃)‧6H₂O, the product was not a Zn^II complex but an N-protonated form of Ant-[12]aneN3. In DNA cleavage experiments with the pUC19 plasmid, Ant-[12]aneN3 also showed DNA photocleavage activity in a Zn^II-independent manner. That is, [12]aneN3 enhances the DNA photocleavage activity of anthracene in a Zn^II-independent manner, unlike bpa (bis(2-picolyl)amine), which was previously reported to enhance DNA cleavage activity by chelating Zn^II. Under physiological conditions, the nitrogen atoms of [12]aneN3 appear protonated without the addition of Zn^II salts and showed an affinity for the negatively charged DNA. The results of this study may facilitate the design of effective DNA cleavage reagents.

In the present study, the stability of a supersaturated solution of indomethacin (IM) was evaluated in hydrophobically modified hydroxypropylmethylcellulose (HM-HPMC) solutions, with and without parent cyclodextrins (CDs). A highly supersaturated state of IM was maintained in the HM-HPMC solution and was further stabilized by the addition of α-CD and β-CD. Notably, the highest level of supersaturation was achieved in HM-HPMC/α-CD solution, which maintained a high concentration of IM for up to 120 h. IM concentrations in these solutions exceeded the amorphous solubility, indicating that phase separation had occurred. To explore this phase separation, Nile Red, a fluorescent probe sensitive to hydrophobic environments, was added to the supersaturated solutions. A higher fluorescence intensity was observed in the HM-HPMC/α-CD solution compared with the HM-HPMC solution, indicating a significant formation of colloidal amorphous aggregates in the supersaturated solution. Cryogenic transmission electron microscopy (Cryo TEM) analysis confirmed the presence of these aggregates, which appeared irregularly shaped. These findings suggest that the combination of HM-HPMC and α-CD effectively stabilized the colloidal amorphous aggregates in the IM supersaturated solution. The addition of α-CD facilitated the dissociation of HM-HPMC into smaller particles, increasing the number of hydrophobic stearyl moieties available for interactions with amorphous IM aggregates, thereby enhancing the stability of the supersaturated state. The combination of HM-HPMC and α-CD offers a promising approach to improving the oral bioavailability of drugs with poor water solubility.

Many antimicrobial peptides (AMPs) exert their activity by disrupting the integrity of the bacterial plasma membrane. One of the membrane-disrupting mechanisms of AMPs involves the formation of toroidal pores, composed of α-helices and lipid headgroups. These pores enable the diffusion of lipid molecules to the opposite leaflet without exposing their headgroups to the hydrocarbon core. Consequently, an increase in lipid transbilayer diffusion (flip-flop) in the presence of AMPs is an important characteristic for AMP structure and function. However, real-time monitoring of the rapid flip-flop in the presence of transmembrane pores has not been achieved because of the permeation of membrane-impermeable reagents and/or the low time resolution of the conventional assays. Herein, we have developed a fluorescence quenching-based flip-flop assay. The flip-flop rates obtained by our method were consistent with those measured by the conventional dithionite reduction assay, confirming the reliability of our approach. The real-time monitoring of the flip-flop process in the presence of the AMP, magainin 2, using the self-quenching assay suggested that the disordered toroidal pores composed of 2 magainin molecules facilitate flip-flop. The newly developed assay will provide a better understanding of the interactions between AMPs and lipid bilayers.

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.

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.