Search Results (753)

Fused and spiro nitrogen-containing heterocycles play an important role as structural motifs in numerous biologically active natural products and pharmaceuticals. The review summarizes various approaches to the synthesis of three-, four-, five-, and six-membered fused and spiro heterocycles with one or two nitrogen atoms. The assembling of the titled compounds via cycloaddition, oxidative cyclization, intramolecular ring closure, and insertion of sextet intermediates—carbenes and nitrenes—is examined on a vast number of examples. Many of the reactions proceed with high regio-, stereo-, or diastereoselectivity and in excellent, up to quantitative, yield, which is of principal importance for the synthesis of chiral drug-like compounds. For most unusual and hardly predictable transformations, the mechanisms are given or referred to. Full article

Noncoplanar spin textures give rise not only to unusual magnetic structures but also to emergent electromagnetic responses stemming from scalar spin chirality, such as the topological Hall effect. In this study, we theoretically investigate nonreciprocal transport phenomena induced by noncoplanar magnetic orderings through microscopic model analyses. By focusing on meron–antimeron spin textures that exhibit local scalar spin chirality while maintaining vanishing global chirality, we demonstrate that the electronic band structure becomes asymmetrically modulated, which leads to the emergence of nonreciprocal transport. The present mechanism arises purely from the noncoplanar magnetic texture itself and requires neither net magnetization nor relativistic spin–orbit coupling. We further discuss the potential relevance of our findings to the compound Gd₂PdSi₃, which has been suggested to host a meron–antimeron crystal phase at low temperatures. Full article

The growing need for developing safer and more effective methods for obtaining enantiomers of chiral compounds, particularly those with pharmacological activity, highlights the potential of biocatalysis as an appropriate pharmaceutical research direction. However, low catalytic activity and stability of free enzymes are often among the substantial limitations to the wide application of biocatalysis. Therefore, to overcome these obstacles, new technological procedures are being designed. In this study, we present optimized protocols for the immobilization of Candida antarctica lipase B (CALB) on an octyl- agarose support, ensuring high enantioselectivity in an organic reaction medium. The immobilization procedures (with drying step), including buffers with different pH values and concentrations, as well as the study of the influence of temperature and immobilization time, were presented. It was found that the optimal conditions were provided by citrate buffer with a pH of 4 and a concentration of 300 mM. The immobilized CALB on the octyl-agarose support exhibited high catalytic activity in the kinetic resolution of (R,S)-1-phenylethanol via enantioselective transesterification with isopropenyl acetate in 1,2-dichloropropane (DCP), as a model reaction for lipase activity monitoring on an analytical scale. HPLC analysis demonstrated that the (R)-1-phenylethyl acetate was obtained in an enantiomeric excess of ee_p > 99% at a conversion of approximately 40%, and the enantiomeric ratio was E > 200. Thermal and storage stability studies performed on the immobilized CALB octyl-agarose support confirmed its excellent stability. After 7 days of thermal stability testing at 65 °C in a climatic chamber, the (R)-1-phenylethyl acetate was characterized by enantiomeric excess of ee_p > 99% at a conversion of around 40% (similar values of catalytic parameters to those achieved using a non-stored lipase). The documented high catalytic activity and stability of the developed CALB-octyl-agarose support allow us to consider it as a useful tool for enantioselective transesterification in organic medium. Full article

Sphingolipids (SLs) are a class of bioactive lipids characterized by sphingoid bases (SBs) as their backbone structure. These molecules exhibit distinct cellular functions, including cell growth, apoptosis, senescence, migration, and inflammatory responses, by interacting with esterases, amidases, kinases, phosphatases, and membrane receptors. These interactions result in a highly interconnected network of enzymes and pathways, known as the sphingolipidome. Dysregulation within this network is implicated in the onset and progression of cardiovascular diseases, metabolic disorders, neurodegenerative disorders, autoimmune diseases, and various cancers. This review highlights the pharmacologically significant sphingoid-based medicinal agents in preclinical and clinical studies. These include myriocin, fingolimod, fenretinide, safingol, spisulosine (ES-285), jaspine B, D-e-MAPP, B13, and α-galactosylceramide. It covers enantioselective syntheses, drug development efforts, and advances in molecular modeling to facilitate an understanding of the binding interactions of these compounds with their biological targets. This review provides a comprehensive evaluation of chiral pool synthetic strategies, translational studies, and the pharmacological relevance of sphingolipid-based drug candidates, offering a pathway for future research in sphingolipid-based therapeutic development. Full article

Chirality plays a key role in the effectiveness and toxicity of bioactive compounds. Usnic acid (UA), a lichen metabolite, exists as two enantiomers. Despite numerous studies on its biological properties, enantioselective aspects remain poorly recognized. This study assessed the cytotoxicity of UA enantiomers against colon, prostate, thyroid, brain, and breast cancer cell lines, as well as non-cancerous cells. Cell viability was determined by the MTT assay after 24, 48, and 72 h. Colon cancer HCT116 cells were the most sensitive (IC₅₀ ~10 µg/mL, 72 h), with no enantiomeric dominance. In prostate cancer PC3 cells, (+)-UA was more effective. Moderate cytotoxic effect was noted for thyroid cancer cells; however, this was evaluated for the first time. MDA-MB-231 breast cancer cells were strongly affected (IC₅₀ 15.8 and 20.2 µg/mL for (+)- and (−)-UA, 72 h), as compared to MCF7 cells. Brain cancer cells were the least affected, as so were normal astrocytes. UA had no effect on normal colon epithelial cells but showed moderate toxicity in prostate, thyroid, and breast cells. To conclude, the overall cytotoxicity of (+)-UA was stronger than its (−)-enantiomer, while the latter compound was more toxic to normal cells. These findings highlight the advantage of (+)-UA, especially in chemopreventive strategies. Full article

Axially chiral compounds play a pivotal role in organic synthesis, materials science, and pharmaceutical development. Among the various strategies for their construction, enantioselective iodination and bromination have emerged as powerful and versatile approaches, enabling the introduction of halogen functionalities that serve as valuable synthetic handles for further transformations. This review highlights recent advances in atroposelective iodination and bromination, with a particular focus on the synthesis of axially chiral biaryl and heterobiaryl frameworks. Key catalytic systems are discussed, including transition metal complexes, small-molecule organocatalysts, and high-valent metal catalysts in combination with chiral ligands or transient directing groups. Representative case studies are presented to elucidate mechanistic pathways, stereochemical induction models, and synthetic applications. Despite notable progress, challenges remain, such as expanding substrate scope, improving atom economy, and achieving high levels of regio- and stereocontrol in complex molecular settings. This review aims to provide a comprehensive overview of these halogenation strategies and offers insights to guide future research in the atroposelective synthesis of axially chiral molecules. Full article

Fluorinated organic molecules have become indispensable in modern chemistry, owing to the unique properties imparted by fluorine to other compounds, including enhanced metabolic stability, controlled lipophilicity, and improved bioavailability. The site-selective incorporation of fluorine atoms into organic frameworks is essential in pharmaceutical, agrochemical, and material science research. In recent years, catalytic fluorination has become an important methodology for the efficient and selective incorporation of fluorine atoms into complex molecular architectures. This review highlights advances in catalytic fluorination reactions over the past six years and describes the contributions of transition metal catalysts, photocatalysts, organocatalysts, and electrochemical systems that have enabled site-selective fluorination under a variety of conditions. Particular attention is given to the use of well-defined fluorinating agents, including Selectfluor, N-fluorobenzenesulfonimide (NFSI), AlkylFluor, Synfluor, and hypervalent iodine reagents. These reagents have been combined with diverse catalytic systems, such as AgNO₃, Rh(II), Mo-based complexes, Co(II)-salen, and various organocatalysts, including β,β-diaryl serine catalysts, isothiourea catalysts, and chiral phase-transfer catalysts. This review summarizes proposed mechanisms reported in the original studies and discusses examples of electrophilic, nucleophilic, radical, photoredox, and electrochemical fluorination pathways. Recent developments in stereoselective and more sustainable protocols are also examined. By consolidating these strategies, this article provides an up-to-date perspective on catalytic fluorination and its impact on synthetic organic chemistry. Full article

Aloysia triphylla is widely used in traditional medicine from Peru for its sedative, digestive and anti-inflammatory properties. However, comprehensive studies on the biological activities of its essential oil (EO), particularly from Peruvian sources, remain limited. This study aimed to analyze the chemical composition and enantiomeric profile of A. triphylla EO and evaluate its antibacterial, antioxidant, anticholinesterase, and cytotoxic activities. The EO was obtained by steam distillation and analyzed using gas chromatography–mass spectrometry (GC-MS). A total of 62 compounds were identified, with (E)-caryophyllene (16.80%), β-pinene (9.96%), and germacrene D (10.00%) being the major components. Enantiomeric analysis revealed specific chiral signatures, including (−)-α-pinene, (+)-limonene, and (R)-(−)-linalool. The EO exhibited significant antibacterial activity, particularly against Bacillus subtilis (MIC = 5 µg/mL), and weak antioxidant activity (IC₅₀ = 7720 and 4648 µg/mL for DPPH and ABTS, respectively). Additionally, the EO demonstrated moderate acetylcholinesterase inhibition (IC₅₀ = 87.8 µg/mL) and cytotoxicity in the Artemia salina assay (LC₅₀ = 964 µg/mL). These findings suggest that A. triphylla EO possesses promising bioactivities with potential applications in pharmaceutical and cosmetic fields. Full article

(−)-Patagonic acid (1) is a clerodane diterpene isolated from several plants from the Alismataceae, Asteraceae, Euphorbiaceae, Fabaceae, Lamiaceae, Salicaceae, Sapindaceae, and Velloziaceae families, and its biological potential as an inhibitor of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) and as an anti-inflammatory compound has been described. Furthermore, the enantiomer (+)-1 is also described in Fabaceae and Verbenaceae. A lack of formal studies about the absolute configuration (AC) determination of 1 is emphasized. Thus, the present manuscript describes the AC determination of patagonic acid (1). The chemical correlation of (−)-1 from (−)-hardwickiic acid (2) was achieved by a simplistic oxidative process. The specific rotation value and electronic circular dichroism (ECD) analysis allowed for the AC determination of (−)-1 as (5R,8R,9S,10R)-(−)-patagonic acid. ECD revealed a positive exciton chirality (EC) phenomenon in both (−)-1 and (−)-2, which is directly associated with their configuration and conformational preferences, which were assessed by DFT calculations at the B3LYP/DGDZVP level of theory. Since the NMR data of (+)-1 are fully coincident with those from its enantiomer studied herein, the chirality of (5S,8S,9R,10S)-(+)-patagonic acid could also be determined. These experimental conclusions deeply complement the literature related to clerodane compounds biosynthesized in several families of plants of scientific interest. Full article

Photosynthetic organisms such as cyanobacteria have the potential for the sustainable production of complex organic molecules due to their ability to use light as an energy source to fix CO₂ and assimilate inorganic nutrients. Over the past decade, large efforts have been put into the metabolic engineering of cyanobacteria to produce various compounds such as alcohols, isoprenoids, biopolymers, and recombinant proteins. Forskolin is a structurally complex labdane-type diterpenoid with eight chiral carbon atoms and is naturally produced in the root cork of the plant Plectranthus barbatus. Forskolin is a potent cAMP activator indicated as a pharmaceutical for a variety of diseases. In the plant, forskolin biosynthesis from geranylgeranyl diphosphate involves six enzymes: two terpene synthases, three cytochrome P450s, and a single acetyltransferase. In this work, we express all six biosynthetic genes from Plectranthus barbatus in Synechocystis sp. PCC. 6803 and demonstrate heterologous production of this complex diterpenoid in a phototroph cyanobacterium. Forskolin titers reached 25.0 ± 4.4 µg/L and the forskolin was entirely secreted into the media. The forskolin-producing Synechocystis strain and empty vector control were cultivated in a photobioreactor for 8 days. Both strains showed similar chlorophyll a contents, and the forskolin-producing strain reached a slightly higher OD₇₃₀ than the control. Forskolin began accumulating in the supernatant after 4 days and increased over time. These results indicate that forskolin production did not negatively impact cell growth. Full article

The stability of collagen, the most abundant protein in humans and many animals, is related to the hydroxylation of L-proline, a post-translational modification occurring at carbon 3 and 4 on its pyrrolidine ring. Collagens of different origins have shown different proline hydroxylation levels, making hydroxyprolines useful biomarkers in structure characterizations. The presence of two chiral carbon atoms, 3-hydroxyproline and 4-hydroxyproline, results in eight stereoisomers (four pairs of enantiomers) whose quantitation in collagen hydrolysates requires enantioselective analytical methods. Capillary electrophoresis was applied for the separation and quantitation of the eight stereoisomers of 3- and 4-hydroxyproline and D,L-proline in collagen hydrolysates. The developed method is based on the derivatization with the chiral reagent (R)-(-)-4-(3-Isothiocyanatopyrrolidin-yl)-7-nitro-2,1,3-benzoxadiazole, enabling the use of a light-emitting diode-induced fluorescence detector for high sensitivity. The separation of the considered compounds was accomplished in less than 10 min, using a 500 mM acetate buffer pH 3.5 supplemented with 5 mM of heptakis(2,6-di-O-methyl)-β-cyclodextrin as the chiral selector. The method was fully validated and showed the adequate sensitivity for the application to samples of collagen hydrolysates. The analysis of samples extracted from chicken Pectoralis major muscles affected by growth-related myopathies showed different stereoisomer patterns compared to those from the unaffected control samples. Full article

Chiral analysis is becoming increasingly important across various scientific fields, including chemistry, pharmaceuticals, biosciences, and more recently, metabolomics. In this context, a high-resolution and high-throughput method was developed for the simultaneous determination of the enantiomeric ratio (er) of seven pairs of amino acid (AA) enantiomers (Arg, Gln, His, Met, Pro, Tyr, and Trp) using flow injection analysis coupled with ion mobility-mass spectrometry (FIA-IM-MS) technology. Specifically, the Single Ion Mobility Monitoring (SIM²) mode on a TIMS-Tof^TM instrument enabled the rapid relative quantification of chiral compound mixtures. A linear model accurately described the relationship between enantiomeric ratio and IM-MS response for Arg, Gln, and Pro enantiomers, as evidenced by high R² values and unbiased residuals. In contrast, non-linear trends were observed for His, Tyr, and Trp, where a quadratic model significantly improved the fit. However, the linear model was retained for Met, despite an R² of about 0.98, due to its comparable performance and simplicity. Measurement accuracy was confirmed with very good recovery rates for er values of 0.95 and 0.99 across all AAs. Finally, the potential of the FIA-SIM²-MS approach in chiral analysis was demonstrated, particularly its ability to provide a reliable and efficient high-throughput tool for accurate er determination. Full article

A tetraerbium cluster containing soft-base dianionic 4,8-difluorobenzo [1,2-d:5,4-d′]bisthiazole-2,6-dithiol (H₂L) ligands, μ-OH, and coordinated 1,2-dimethoxyethane (DME) of the general formula {Er₄(μ-L)₄(μ-OH)₄(DME)₄} (1) was synthesized using a one-pot method. X-ray analysis revealed that 1 is an asymmetrical tetramer in which there are four μ₂-bridging bisthiazole ligands and four μ₂-bridging hydroxide anions per four erbium ions. The molecule of 1 has inherent chirality, and the geometry of intramolecular F…F short contacts implies the formation of a classical halogen bond. Upon excitation by a 375 nm diode laser, compound 1 shows the moderate metal-centered emission of Er³⁺ ions that peaked at 1530 nm. Full article

Broccoli, a highly valued Brassica vegetable, is renowned for its rich content of bioactive substances, including glucosinolates, phenolic compounds, vitamins, and essential minerals. Glucosinolates (GSLs), secondary plant metabolites, are particularly abundant in broccoli. The global consumption of broccoli has increased due to its high nutritional value. This review examines the essential bioactive compounds in broccoli and their biological properties. Numerous in vitro and in vivo studies have demonstrated that broccoli exhibits various biological activities, including antioxidant, anticancer, antimicrobial, anti-inflammatory, anti-obesity and antidiabetic effects. This review analyzes several aspects of the chemical and biological activity of GSLs and their hydrolysis products, isothiocyanates such as sulforaphane, as well as phenolic compounds. Particular emphasis is placed on sulforaphane’s chemical structure, the reactivity of its isothiocyanate fraction (-NCS), and given the different behavior of SFN enantiomers, a wide and detailed review of the chemical synthesis methods described, by microbial oxidation, or using a chiral ruthenium catalyst and more widely using chiral auxiliaries for synthesizing sulforaphane enantiomers. In addition, the methods of chiral resolution of racemates by HPLC are reviewed, explaining the different chiral fillers used for this resolution and a third section on resolution using the formation of diastereomeric complexes and subsequent separation on achiral columns. Additionally, this review highlights the presence of antimicrobial peptides in broccoli, which have shown potential applications in food preservation and as natural alternatives to synthetic antibiotics. The antimicrobial peptides (AMPs) derived from broccoli target bacterial membranes, enzymes, oxidative stress pathways and inflammatory mediators, contributing to their effectiveness against a wide range of pathogens and with potential therapeutic applications. Full article

Ferroelectric liquid crystals (FLCs) are key materials for high-speed electro-optical applications, yet achieving optimal properties over a broad temperature range down below room temperature remains a challenge. This study presents a novel series of systematically designed FLC mixtures, incorporating components with three degrees of chirality—achiral systems, with one center of chirality and with two centers of chirality—to optimize the mesomorphic stability, electro-optical response, and physicochemical properties. The strategic doping by chiral components up to a 0.2 weight fraction extends the temperature range of the ferroelectric phase while lowering the melting temperature. Notably, mixtures containing two chiral centers exhibit shorter helical pitches, while increasing chirality enhances the tilt angle of the director and spontaneous polarization. However, in a mixture containing all three types of chirality (CchM), spontaneous polarization decreases due to opposing vector contributions. Switching time analysis reveals that a system with achiral components and those with two centers of chirality (A-BchM) exhibits the fastest response, while CchM demonstrates only intermediary behavior, caused by its high rotational viscosity. Among all formulations, those containing compounds with two centers of chirality display the most favorable balance of functional properties for deformed helix ferroelectric liquid crystal (DHFLC) applications. One such mixture achieves the lowest melting temperature reported for DHFLC-compatible FLCs, enabling operation at sub-zero temperatures. These findings pave the way for next-generation electro-optical devices with enhanced performance and appropriate environmental stability. Full article