Chemical & pharmaceutical bulletin最新文献

Two new glycosides, named 3-methoxy-5-methylphenol-6-O-β-glucopyranosyl-(1→6)-β-glucopyranoside (compound 1) and 1-O-feruloyl-α-arabinofuranosyl-(1→6)-β-glucopyranoside (compound 2), were isolated from Asiasarum root, together with eight known compounds. Asiasarum root (crude drug name in Latin: ASIASARI RADIX) is well known for its anti-inflammation and antitussive properties and is commonly found in Kampo formula in Japan. The structures of new compounds 1 and 2 were characterized using one- and two-dimensional (1D and 2D) NMR spectroscopy and MS. In addition, the anti-glycation activity of the isolates was evaluated. Glycation is particularly advanced in patients with diabetes and is suspected to be associated with diabetic complications such as nephropathy, osteoporosis, and Alzheimer's disease. The inhibition of this reaction is thought to be linked to the prevention and treatment of these diseases. Compounds 2 (79.4%), 4 (82.4%), 5 (79.8%), 6 (86.5%), 7 (90.1%), 9 (61.4%), and 10 (82.2%) showed activities comparable to that of aminoguanidine (45.3%) used as a positive control.

Conventional peptide synthesis involves multiple protection and deprotection steps, and typically relies on stoichiometric amounts of coupling reagents and additives. This makes the process cumbersome, and results in poor atom economy and hazardous waste generation. Therefore, direct peptide bond formation using unprotected amino acids is a promising alternative. However, this approach presents some challenges: 1) Solubility of unprotected amino acids in organic solvents; 2) Control of undesired side reactions; 3) Chemo-selective activation of the carboxylic acid group in the presence of an amine functionality; and 4) Epimerization. To address these challenges, we developed tris(2,2,2-trifluoroethoxy)silane [H-Si(OCH₂CF₃)₃], a cost-effective and accessible coupling reagent. This single reagent efficiently synthesizes N-terminal free peptides from unprotected amino acids and amino acid tert-butyl esters, without the need for any additives. H-Si(OCH₂CF₃)₃ enhances amino acid solubility through coordinating with both termini and plays a dual role, serving as a transient amine-protecting group and as a carboxylic acid activating or promoting reagent for peptide bond formation. This method is operationally simple and versatile, enabling the efficient synthesis of N-terminal free peptides from unprotected amino acids and amino acid tert-butyl esters, with good yields, high optical purity, and broad side-chain compatibility.

This study evaluated the cadmium (Cd) adsorption characteristics of sugarcane bagasse (BG) calcined at different temperatures (200-1000°C). The point of zero charge (pH_pzc) of the BGs ranged from 4.3 to 6.5. The amount of Cd adsorbed was higher at pH 4-8 than at pH 2. These results indicate that the negative charge on the BG surface and the presence of Cd(II) cations are important for Cd adsorption. Meanwhile, the amount of Cd adsorbed and the specific surface area (SSA) of BG increased with increasing calcination temperature of BG. Furthermore, a partial correlation analysis revealed that acidic surface functional groups (SFGs) were also significantly associated with Cd adsorption, independently of SSA. These results suggest that both SSA and acidic SFGs jointly contribute to Cd adsorption.

Antibody-based therapeutics have shown remarkable success in targeting extracellular molecules, yet their application to intracellular targets remains largely unexplored due to the absence of efficient delivery systems. The large molecular weight and hydrophilicity of immunoglobulin G (IgG) make cytosolic delivery particularly challenging. Previously, we developed a cytosolic delivery peptide, E3MPH16, based on a modified Mastoparan X sequence, which enabled efficient delivery of macromolecules such as dextran with minimal cytotoxicity. However, effective intracellular delivery of antibodies required high concentrations, limiting its practical utility. In this study, we aimed to enhance delivery efficiency while preserving low toxicity by introducing d-amino acid substitutions into E3MPH16. The resulting peptide, e3MPH16, incorporates d-glutamic acid residues at the N-terminus to improve serum stability and protease resistance. Functional analyses demonstrated that e3MPH16 significantly improves cytosolic delivery of Cre recombinase and antibodies compared with the original E3MPH16, without increasing membrane-lytic activity or cytotoxicity. These results underscore the potential of d-amino acid-substituted peptides such as e3MPH16 as a promising platform for the intracellular delivery of unmodified functional antibodies.

The pandemic of coronavirus disease 2019, caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a serious concern worldwide. Although some effective vaccines have been developed, only a few anti-SARS-CoV-2 drugs have been approved for their clinical use. In this study, we designed and synthesized new anti-SARS-CoV-2 drugs based on the chemical structure of amodiaquine, which is known as an antimalarial drug. Consequently, we have identified amodiaquine analogs functionalized with dialkylamino-pendant aminophenol moieties that possess a high level of anti-SARS-CoV-2 activity with a low level of toxicity.

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.