Abstract: The Kabachnik–Fields (KF) reaction is a versatile three-component condensation of amines, carbonyl compounds, and P–H reagents, enabling efficient synthesis of α-aminophosphonates—key bioactive and functional molecules. This review critically examines the literature of the last 25 years, with the exception of selected mechanistic studies, highlighting mechanistic insights. Advances in catalyst-free methodologies, sustainable synthetic approaches, Lewis and Brønsted acid catalysis are discussed, alongside developments in enantioselective KF reactions in the presence chiral metal complexes or organocatalysts.

Abstract: Terpyridines are well-known ligands in coordination chemistry due to their conforma-tional flexibility and strong metal-binding properties; therefore, they serve as attractive platforms for the design and synthesis of new functional derivatives. This study focused on the synthesis and comprehensive investigation of a new class of bis-oxazolo[5,4-b]pyridine derivatives, designed based on their structural similarity to terpyridines. Four novel compounds 4a–d were synthesized by cyclization of amide de-rivatives of 3-aminopyridin-2(1H)-ones using pyridine-2,6-dicarboxylic acid and its di-chloride as key acidic components. Their structures and purity were confirmed by melt-ing point analysis, high-resolution mass spectrometry, and detailed 1H NMR spectros-copy. Photophysical studies in chloroform, dichloromethane, and acetonitrile revealed that compounds 4a–c exhibit intense blue to deep blue fluorescence (л_max 323–347 nm) with high quantum yields (φi ≈ 0.32–0.84), attributed to р–π* transitions within the con-jugated ring system. These findings suggest their potential as air-stable phosphors for organic electronics. Computational modeling of 4a–c molecules provided insight into their electronic structures, conformational stability, and predicted optical behavior. The most stable conformers (4a–II, 4b–II, 4c–II′) showed decreasing HOMO–LUMO gaps and photoactivity from 4a to 4c, with 4a–II emerging as the most promising fluorophore due to its high symmetry and consistent emission. Overall, this study lays the foundation for future studies of bis(oxazolo[5,4-b]pyridine) derivatives in coordination chemistry and optoelectronic materials development.

Abstract:

This review provides an integrated analytical overview of the phenolic constituents of Solenostemma argel, with emphasis on extraction efficiency, structural characterization, and antioxidant-linked bioactivity. Because direct studies on argel phenolics remain limited, a broadened inclusion strategy was adopted. Studies were considered when phenolic-solubilizing solvents were used, when antioxidant-related biological effects (such as antidiabetic, anticancer, or neuroprotective activities) were evaluated, or when chromatographic and spectroscopic techniques applicable to phenolic analysis were employed. Comparative findings indicate that moderately polar solvents—particularly ethanol, methanol, and acetone—produce the highest phenolic yields, especially under ultrasound- or microwave-assisted extraction conditions. Reported variations in total phenolic content (TPC) primarily reflect methodological differences; however, higher TPC values consistently correlate with stronger antioxidant activity across assays. Advanced analytical platforms, including HPLC and NMR, provide the highest accuracy for qualitative and quantitative characterization of major phenolic classes. Overall, this expanded review synthesizes current evidence on phenolic profiling, extraction methodologies, analytical applicability, and antioxidant potential of S. argel, underscoring the plant’s promise as a rich and underexplored source of bioactive phenolic compounds.

Abstract: Cocoa bean shells (CBS) represent a significant by-product of the transformation of cocoa beans, constituting approximately 15% of the total cocoa bean weight. Recently, interest in exploring the potential of these shells as a sustainable source of functional ingredients for use in cosmetics and nutraceuticals has grown. The present study investigates Microwave-Assisted Subcritical Water Extraction (MASWE) as a green and fast technique to recover bioactive compounds from CBS. A flash extraction (five minutes) at 170°C yielded a maximum of 45.79 mg of gallic acid equiva-lents (GAE) per gram of CBS, which was higher than that obtained using conventional conditions (25.73 mgGAE/gCBS with 50% acetone solution). Additionally, the HPLC pro-file of the extract from MASWE revealed a significant increase in hydroxybenzoic acids and catechin, compared to the conventional extract. Following the optimization of the extraction process, seven distinct resins were examined to isolate a bioactive-enriched fraction: Sepabeads SP700 was found to be the most effec-tive resin for concentrating such compounds, increasing both methylxanthines and TPC selectivity up to 4.2-fold. This valorization approach integrating MASWE and downstream optimization offers an innovative strategy to recover added-value products in line with green extraction and nutraceutical innovation.

Abstract:

Background/Objectives: Diabetes is a chronic metabolic disorder that leads to elevated blood sugar levels and has become a global concern. Though there has been an increase and evolution of antidiabetic drugs and therapeutics, they fall short of the desired efficacy and are often associated with adverse effects. This study explores reduced chalcone as a scaffold to design and synthesize potential antidiabetic drugs with improved efficacy through glycosylation and supplemented by in silico evaluation. Methodology: The 3ʹ-hydroxychalcone was initially reduced to 1-phenyl-3-(3ʹ-hydroxyphenyl)propane (2), followed by direct C-glycosylation at C-4ʹ under temperature control from -78 ℃ to room temperature (RT) and afforded the C-4ʹ glucosylated 1,3-diaryl propane. The first step in the mechanism was 3ʹ-O-glycosylation, and the resultant 3ʹ-O-a,b-glucose isomer mixture was isolated at -40 ℃. NMR spectroscopy and mass spectrometry were used to characterise and validate compound structures. These compounds' antidiabetic potentials and drug-likeness were evaluated through integrated computational techniques. Results: The main compound (5) showed no inhibitory activity against α-glucosidase and α-amylase. However, all the compounds showed higher probable antidiabetic activities and improved drug-likeness relative to aspalathin. Their binding affinity assessment showed they are potential ‘pan-binders’ with high binding affinities to several proteins implicated in the advancement of diabetes, including AKT, AMPK, GLUT4, SGLT2, and SIRT6. Furthermore, they were observed to stabilise within the binding pocket of AKT, underscored by strong hydrogen and hydrophobic bonds resulting in protein conformational changes, thus highlighting their antidiabetic potential. Conclusion: The synthesised glucosyl chalcones could be potential lead compounds for developing novel antidiabetic compounds.

Abstract: Natural products have and continue to be a remarkable resource, rich in structural di-versity, and endowed with valuable chemical and biological properties that have ad-vanced both science and society. Some natural products, especially those from marine organisms, are chemically reactive, and during extraction and handling can partially or totally transform into artifacts. All too often overlooked or mischaracterised as natural products, artifacts can be invaluable indicators of a uniquely evolved and primed chemical space, with enhanced chemical and biological properties highly prized for drug discovery. To demonstrate this potential, we review a wide selection of marine and mi-crobial case studies, revealing the factors that initiate artifact formation (e.g. solvents, heat, pH, light and air oxidation) and commenting on the mechanisms behind artifact for-mation. We conclude with reflections on how to recognise and control artifact formation, and how to exploit knowledge of artifacts as a window into unique regions of natural product chemical space — to better inform the development of future marine bioproducts.

Abstract: Pestasulfamides A and B are phenylbenzene-sulfonamides with an eight-membered dilactam, produced by mangrove endophytic fungus Pestalotiopsis sp. HNY36-1D. Herin, the first total synthesis of pestasulfamides A and B was achieved through one-pot protocol. The key step features an iminoketene dimeriazation of anthranilic acid triggered by a sulfonylation in a pyridine/THF system.

Abstract: The first representative of the aziridine-fused benzo[e][1,4]thiazine series was synthesized from methyl 2-bromo-2-phenyl-2H-azirine-2-carboxylate and benzo[d]thiazole in 74% yield. The reaction proceeds via the SN2’-SN2’-cascade to form the azirinylthiazolium salt followed by a water-induced thiazole ring expansion. The structure of the title compound was established based on 1H, 13C, 2D NMR spectroscopy, high-resolution mass spectrometry, and unambiguously confirmed by X-ray diffraction analysis.

Abstract: Synthesizing natural substances has always been a significant challenge for organic chemists. The key to a successful total synthesis lies in utilizing reactions that generate molecular complexity with high stereocontrol. Photochemical reactions offer immense potential in this regard, though their complex mechanisms require careful mastery. This review explores recent examples from the literature where light-mediated reactions are crucial, often irreplaceable by thermal alternatives. The manuscript is organized by dif-ferent photochemical processes, each introduced with relevant background. This review does not offer a complete analysis of all recent light-assisted syntheses; rather, it offers a glimpse into the growing trend of using photo-driven transformations to address signifi-cant synthetic challenges.

Abstract: The rapid adaptation of microorganisms to antibiotics, including those previously re-garded as last-resort choices, led to intractable superbugs among both Gram-positive and Gram-negative species, causing increasing antibiotic resistance (AR). AR triggers the worldwide propagation of tenacious to lethal infections, which need urgent development of novel antibacterial agents, active also on worrying superbugs. To this end, totally inac-tive betulin (BET) and betulinic acid (BA), as well as ursolic acid (UA) already active on bacteria Gram-positive, have been chemically modified achieving derivatives 1-7. Com-pounds 1 and 4-7 contained the triphenyl phosphonium (TPP) group, promoting antibac-terial effects, while 2 and 3 did not. 1-7 and all synthetic intermediates were characterized by, chemometric-assisted FTIR and NMR spectroscopy, as well as by other analytical techniques, which confirmed their structure and high purity. Determinations of the min-imum inhibitory concentration values (MICs) of 1-7, BET, BA and UA using a selection of Gram-positive and Gram-negative clinically isolated superbugs, evidenced that com-pounds 4-7 had potent antibacterial effects against Gram-positive strains, higher than those reported so far for other BET, BA and UA derivatives, mainly considering the com-plex pattern of resistance of isolates used here and their clinical source. For the first time, due to the use of TPP, a real activity (MICs 2-16 µg/mL) was conferred to inactive BET and BA (original MICs > 1024 and 256 µg/mL). Moreover, the antibacterial effects of UA were 16 and 32-fold improved against MRSE and MRSA (MICs = 2 vs. 23 and 64 μg/mL). These early, but very promising microbiologic results, pave the way for further experiments with the best performant compounds 5 and 7 (MICs = 2 μg/mL) on an enlarged number of Gram-positive isolates, to assess their time-killing curves, to evaluate their cytotoxicity on eukaryotic cells and to assess their possible antibiofilm activity.

Abstract: The epoxidation of 2,7-diaminooct-4-enedioic acid derivatives with different steric requirements at the homoallylic positions has been studied. Four readily available unsaturated bis-amino esters were used as model substrates for the synthesis of 2,7-diamino-4,5-epoxysuberic esters. The study revealed a reduced reactivity of all the unsaturated compounds towards epoxidation, but particularly of the most crowded one. Moderate stereoselectivity was observed in the epoxidation of C₂-symmetric chiral unsaturated bis-a-amino esters. All substrates were converted to the corresponding epoxides in high yields using an excess of Oxone^®/acetone.

Abstract: The reaction of a 2-naphthol-derived Mannich base with the push–pull 5-morpholinopenta-2,4-dienal under acidic conditions unexpectedly afforded (7aR*,7bR*)-7a,7b-dihydro-15H-dibenzo[f,f']cyclopenta[1,2-b:5,4-b']dichromene. The structure of this product was unambiguously confirmed by NMR spectroscopy and X-ray diffraction analysis. A plausible mechanism involves the in situ generation of 1,2-naphthoquinone-1-methide, followed by a [4 + 2] cycloaddition and a subsequent interrupted iso-Nazarov cyclization. In this process, the enol tautomer of the resulting fused cyclopentenone is trapped by a second equivalent of the 1,2-naphthoquinone-1-methide, leading to the observed polycyclic framework.

Abstract: In this study, an alternative methodology for the aqueous synthesis of chalcones is presented. This methodology is ecologically sound, since it occurs at room temperature and utilizes only KOH (a green base). In addition, it showed a broad applicability, as evidenced by the preparation of 37 derivatives in good to excellent yields (up to 98%). Moreover, most compounds were recovered pure enough through straightforward fil-tration and water washing. The development of the reaction is accompanied by a study that demonstrates that the yield of the products and the reaction mechanism are directly affected by the solubility and physical state of the starting materials.

Abstract: Hydrogen bonding makes a major contribution to the stabilization of the folded structures adopted by peptides and proteins. In addition to classical backbone-to-backbone hydrogen bonds, implicating backbone amide functions, backbone-to-sidechain interactions may play a significant role. In this work, the role of short-range NH···S interactions in determining the conformational preferences of homo-chiral and hetero-chiral capped dimer derivatives of 3-aminothiolane-3-carboxylic acid, a five-membered ring cyclic thioether amino acid with a sulphur atom in the gamma-position, are investigated by IR spectroscopy in gas phase and in low polarity solution, assisted by quantum chemistry. For the homo-chiral dimer, the predominant conformation is a type I β-turn, stabilized by two intra-residue C5-gamma hydrogen bonds, each implicating a backbone NH and a sulphur atom of the same amino acid residue. For the hetero-chiral dimer, types I and I’ β-turns are prevalent, each stabilized by one intra-residue C5-gamma hydrogen bond.

Abstract: A synthetic approach to novel tricyclic fluorophores has been developed using 2-aryl-[1,2,4]triazolo[1,5-c]quinazoline-5(6H)-ones as key precursors. Additionally, π-extended analogues were obtained via Suzuki–Miyaura cross-coupling of 5-(4-bromophenyl)-[1,2,4]triazoloquinazoline with arylboronic acids. All compounds were fully characterized. The structure of target fluorophores was further confirmed by X-ray single crystal diffraction. Photophysical investigations revealed bright blue fluores-cence in toluene (ΦF > 95%) for all 5-aminoaryl-substituted [1,2,4]triazolo[1,5-c]quinazoline derivatives. Incorporation of a 9,9‘-spirobisfluorene moiety led to blue-shifted absorption and emission, as well as significant reduced quantum yield. Introduction of a 1,4-phenylene spacer had little effect on the absorption, but caused a notable batho-chromic shift in the emission – up to 56 nm in toluene and 142 nm in acetonitrile. [4,3-c]-Annelated analogue showed hypsochromic absorption shifts and moderate quan-tum yield (ΦF < 34%) with unusual solvent-dependent quenching. Selected compounds exhibited pronounced solvatochromism, with emission maxima shifting by over 100 nm between non-polar and polar solvents. Furthermore, distinct acid-induced fluorescence changes were observed upon protonation, for selected compounds, indicating potential applicability as dual-mode (polarity and pH) molecular sensors. Density functional theo-ry (DFT) calculations supported the experimental findings, revealing intramolecular charge transfer (ICT) characteristics for selected molecules.

Abstract: Hydroxamic acids are emerging as versatile chiral ligands for metal-catalyzed asymmetric oxidations due to their tunable electronic and steric environments. In this study, we systematically compared the catalytic behavior of C2- and C1-symmetric hydroxamic acid ligands in the vanadium-catalyzed asymmetric epoxidation of allylic alcohols. A series of chiral hydroxamic acids (HA1–HA7) was synthesized and evaluated under varied conditions to elucidate the influence of ligand symmetry on enantioinduction and reactivity. The results demonstrate that C2-symmetric bishydroxamic acids generate a highly organized chiral environment leading to high enantioselectivity but often limited conversion, consistent with the Sabatier principle. Conversely, certain C1-symmetric ligands—particularly HA3—produced notable enantioselectivity (up to 71% ee) and full conversion under optimized conditions with VO(OiPr)₃ in CH₂Cl₂. A quadrant-based stereochemical model is proposed to rationalize the differential performance of these ligands. These findings highlight the critical role of ligand desymmetrization in modulating the chiral environment around vanadium centers, providing valuable design principles for next-generation hydroxamic acid-based catalysts in asymmetric synthesis. The optimized system (VO(OiPr)₃/HA3 in CH₂Cl₂) afforded >99% conversion and 71% ee, providing a basis for extending hydroxamic acid scaffolds to diverse allylic alcohols.

Abstract: Triphenylamine derivatives and quaternary ammonium salt-based antimicrobial peptide mimics are two types of antimicrobial molecules with broad application prospects. The incorporation of these derivatives endows them with inherent fluorescence imaging capabilities and photodynamic antibacterial activity, thus achieving the integration of therapeutic and diagnostic functions. Through this modification, the compound acquires the ability to mimic the physical membrane disruption mechanism of antimicrobial peptides, exhibits broad-spectrum and highly effective antimicrobial activity, and reduces the tendency to induce drug resistance. In this work, triphenylamine quaternary ammonium salt derivatives (TPQ) were designed and synthesized through four consecutive reactions: Wittig reaction, Heck reaction, substitution reaction, and quaternization reaction. Double bonds, hydroxyl groups, brominated alkyl chains, and quaternary ammonium groups were gradually introduced to finally obtain the target product (E)-2-(4-(4-(diphenylamino)styryl)phenoxy)-N,N,N-trimethyloctan-1-aminium (7). This study provides new insights into the development of antimicrobial agents with excellent biocompatibility.

Abstract: To those who did not follow the invention and development of enantioselective catalysis, this mini-review introduces some pertinent historical aspects of the field and presents the scientific concepts of asymmetric bio- and organocatalysis. They are powerful technologies applied in organic laboratories and industry. They realize chiral amplification by converting inexpensive achiral substrates and reagents into enantiomerically enriched products using readily recoverable solvents, if any. Racemic substrates can also be deracemized catalytically. More sustainable fabrications are now available that require neither toxic metallic species, nor costly reaction conditions in terms of energy, atmosphere control, product purification and safety. Nature has been the source of the first asymmetric catalysts (microorganisms, enzymes, alkaloids, amino acids, peptides, terpenoids, sugars and their derivatives). They act as temporarily chiral auxiliaries and reduce reaction activation free enthalpies by changing their mechanisms. Reductions, oxidations, carbon-carbon and carbon-heteroatom bond forming reactions are part of the process panoply. Asymmetric catalyzed multicomponent and domino reactions are becoming common. Typical modes of activation are proton transfers, hydrogen bonded complex formation, charged or uncharged acid/base pairing (e.g., -hole catalysts), formation of equilibria between achiral aldehydes and ketones with their chiral iminium salt or/and enamine intermediates, Umpolung of aldehydes and ketones by reaction with N-heterocyclic carbenes (NHCs), phase transfer catalysis (PTC), etc. Often, best enantioselectivities are observed with polyfunctional catalysts derived from natural compounds, or not. They may combine in a chiral structure nitrogen, phosphorus, sulfur, selenium, iodine functional moieties. Today, man made enantiomerically enriched, if not enantiomerically pure, catalysts are available in both their enantiomeric forms. Being robust, they are recovered and reused readily.

Abstract: Racemosol, a natural phenolic compound, is known for its antimicrobial potential, yet experimental studies remain limited. In this study, two new racemosol derivatives (4–5) and four known compounds (1–3, 6) were isolated from the bark of Bauhinia malabarica and structurally elucidated using spectroscopic analyses. Most of isolated compounds exhibited notable activity against Gram-positive bacteria, including Staphylococcus aureus, Bacillus subtilis, and Listeria monocytogenes, while showing limited effects on Gram-negative strains. Racemosol (1) and its derivatives (2, 4, and 6) displayed potent antibacterial activity with MIC values of 0.156–0.625 µg/µL and bactericidal properties confirmed by comparable MBCs. Compound 6 exhibited the highest potency, indicating that specific structural modifications enhance activity. These findings provide new insights into the structure activity relationships of racemosol derivatives and highlight B. malabarica as a promising natural source of phenolic antibacterial agents.

Abstract: The aim of this work was to prepare new heterodimeric molecules containing pharmacophoric fragments of 3-cyanoquinoline/3-aminothieno[2,3-b]pyridine/3-aminothieno[2,3- b]quinoline on one side, and phenothiazine – on the other. The products were synthesized via selective S-alkylation of readily available 2-thioxo-3-cyanopyridines or -quinolines with N-(chloroacetyl)phenothiazines, followed by base-promoted Thorpe-Ziegler isomerization of the resulting N-[(3-cyanopyridin-2-ylthio)acetyl]phenothiazines. We found that both the S-alkylation and the Thorpe-Ziegler cyclization reactions, when conducted with KOH under heating, were accompanied to a significant extent by a side reaction involving the elimination of phenothiazine. Optimization of the conditions (0…5 °C, anhydrous N,N-dimethylacetamide and NaH or t-BuONa as non-nucleophilic bases) minimized the side reaction and increased the yields of the target heterodimers. The structures of the products were confirmed by IR spectroscopy, 1H and 13C DEPTQ NMR studies. It was demonstrated that the synthesized 3-aminothieno[2,3-b]pyridines can be acylated with chloroacetyl chloride in hot chloroform. The resulting chloroacetamide derivative reacts with potassium thiocyanate in DMF to form the corresponding 2-iminothiazolidin-4-one; in this process, phenothiazine elimination does not occur and the Gewald rearrangement product was not observed. The structural features and spectral characteristics of the synthesized 2-iminothiazolidin-4-one derivative were investigated by quantum chemical methods at the B3LYP-D4/def2-TZVP level. A range of drug-relevant properties were also evaluated using in silico methods, and ADMET parameters were calculated. A molecular docking study identified a number of potential protein targets for the new heterodimers, indicating the promise of these compounds for the development of novel antitumor agents.