Abstract: Five novel α-aminophosphonates 1-5 were synthesized from a natural product, vanillin, heterocyclic 2-aminobenzothiazole primary amines, and diisopropyl phosphite in a one-pot Kabachnik-Fields reaction with ionic liquid [bmim][PF6] as a catalyst under heating conditions. The structures of the obtained compounds were elucidated by spectral analysis of 1H-NMR, 13C-NMR, 31P-NMR, IR, and HRMS. The UV spectra of 1-5 were measured in five different solvents. The fluorescent properties of 1-5 were examined at 0.1 μM in methanol, ethanol, acetonitrile, 1,4- dioxane, and ethyl acetate. Antimicrobial results revealed that compound 5 showed antibacterial activity, inhibiting Bacillus subtilis by 72.7% at 2.0 mg/mL. Compounds 1-5 showed higher fungal inhibitory activity than the positive control, fluconazole, at concentrations of 3.125-100 μg/mL.
Abstract: While conjugated dienes are readily accessible as Z/E isomeric mixtures, their stereoselective functionalization remains challenging. Stereoconvergent conjugate addition addresses this challenge by enabling the conversion of these isomeric mixtures into geometrically defined alkenes. This mini review highlights recent advances and mechanistic principles underlying stereoconvergent conjugate addition, with a particular focus on substrate pre-isomerization and shared allylmetal intermediate pathways. We conclude by discussing emerging challenges, such as extending to longrange conjugated systems, overcoming steric barriers in multisubstituted substrates, and achieving stereoconvergence in complex multi-isomer systems.
A group of 2-(4-aryl)-3-(cyclohexylimino)-2-hydroxy-2,3-dihydro-1H-imidazo[1,2- a]pyridin-4-ium chlorides was successfully synthesized in moderate yields through the reaction of Nef-Adducts (α-keto imidoyl chlorides), which were generated from the interaction of N-cyclohexyl isocyanide with aryl carbonyl chlorides, followed by the incorporation of 2-aminopyridine. The imidazo[1,2-a]pyridin-4-ium chlorides produced were thoroughly characterized in this study, and the X-ray crystal structures of their salts were determined. This research examines the antimicrobial properties of the prepared compounds against various microbial strains. The findings suggest that compounds 7b and 7d exhibit the broadest and most potent activity.
Abstract: Carbon disulfide (CS2) has been widely recognized as a versatile building block in chalcogen chemistry and has attracted the research community to the synthesis of a variety of highly functionalized organic scaffolds. Conversely, carbon disulfide (CS₂) serves as a valuable chemical synthon due to its wide availability from various inexpensive sources and remarkable stability, making it a crucial substrate in organic chemistry. CS2 exhibits a versatile reactivity under mild ambient conditions for the synthesis of a library of S-containing biologically important molecules. The electrophilic nature of the carbon center, combined with the nucleophilicity of the sulfur atoms, enables CS2 to participate in a wide array of reactions, making it a key sulfur source for the introduction of sulfur functionalities into organic molecules. Moreover, the ambident nature of CS2 allows it to interact effectively with a range of nucleophiles, including amines, thiols, and organometallic reagents, leading to key intermediates such as dithiocarbamates and xanthates. This review summarizes recent developments in the use of carbon disulfide for the preparation of novel organosulfur compounds under mild reaction conditions. The sustainable techniques employed herein involve the use of non-toxic, low-cost, commercial-grade reagents and environmentally benign, greener solvents. By summarizing recent developments, this review aims to inspire further research in advancing the green synthesis of organosulfur compounds.
Abstract: Jatrophane diterpenes represent a structurally intricate family of macrocyclic diterpenoids characterized by a highly oxygenated framework and diverse biological properties, including Pglycoprotein modulation and anti-inflammatory activity. Their densely functionalized [5+12] bicyclic core and multiple stereocenters pose significant synthetic challenges, prompting continued interest in efficient chemical access to these molecules and related analogues. In this study, we describe our synthetic efforts toward the cyclopentane unit, i.e., the five-membered core of jatrophanes, as a key intermediate, guided by retrosynthetic analysis. The target cyclopentane segment was synthesized in nine steps from TBSO(CH2)3-COOH in an overall 24% yield. Key features of the synthesis include an anti-selective Evans aldol reaction and a ring-closing metathesis/selective hydrogenation sequence, which enabled the construction of the densely functionalized cyclopentane framework. These results provide a practical foundation for the total synthesis of the target jatrophane diterpene and for the preparation of its derivatives.
Abstract: Chiral cationic catalysts direct reactivity and stereocontrol through synergistic ion-pairing interactions and chiral environment enforcement, enabling asymmetric transformations. This minireview highlights the recent advances in quaternary ammonium/phosphonium, chalcogenonium salts, bisguanidinium catalysts, and metal-cooperative systems, presenting their potential in C–X bond formation and cyclization. Over the past five years, rational catalyst design, guided by computational modeling, has also gained increasing prominence. This strategy facilitated the rapid discovery of novel cationic scaffolds and provided mechanistic insights, thereby enabling precise stereocontrol and broadening the accessible substrate scope. The future perspective of chiral cation catalysts centres on developing robust, tunable frameworks, integrating multi-catalytic systems, leveraging machine learning for optimization, and enabling sustainable and highly selective asymmetric transformations.
The study presents a targeted approach to synthesizing and characterizing novel cyanine dyes containing bis-pyrazolo moieties. It introduces asymmetrical monomethine (compound 3) and symmetrical aza-hexamethine dyes (compounds 4a-d), synthesized via an intermediate (compound 1). A key feature of these dyes is their strong intramolecular charge-transfer, which enhances electronic transitions and contributes to their vivid optical properties. They also exhibit pronounced solvatochromism shifts in absorption spectra based on solvent polarity, making them sensitive to environmental factors such as pH and molecular surroundings. This responsiveness suggests their potential as molecular probes for sensing applications. Furthermore, the study evaluates the cytotoxic activity of compounds 1, 4a, and 4b against two tumor cell types, namely prostate (PC-3) and mammary epithelial cells (MCF-7). The results demonstrate promising bioactivity, indicating potential for future biomedical applications, particularly in cancer diagnostics and therapy. Overall, the research introduces bis-pyrazolo cyanine dyes that exhibit prominent electronic and structural features compared to conventional cyanine dyes, enabling a unique photophysical manner.
Coumarins are an important class of oxygen-containing heterocyclic secondary metabolites which exhibits wide range of applications in synthetic, therapeutic, and material chemistry. They are well known for their varied bioactive properties, including anticancer, anticoagulant, antiinflammatory, antimicrobial, antiviral, and antioxidant activities. In addition to their medicinal uses, coumarin derivatives are broadly useful as fluorescent probes, laser dyes, and functional materials. Despite their importance, many classical synthetic routes to coumarin, such as the Pechmann, Knoevenagel, Perkin, and Wittig reactions, often require toxic reagents, acids, or moisture-sensitive catalysts under harsh conditions. These disadvantages limit their compatibility with the environment and industries. In recent years, [Ln(OTf)₃] have emerged as efficient and versatile Lewis acid catalysts for the preparation of coumarins. The distinctive catalytic features of Ln(OTf)₃, such as strong Lewis acidity, high oxophilicity, water tolerance, and thermal and chemical stability, enable their use in aqueous media and under solvent-free conditions. These properties facilitated a range of coumarinforming transformations, including the Pechmann condensation, the Knoevenagel condensation, and multicomponent reactions. Ln(OTf)₃-mediated approaches have enabled the provision of structurally diverse and biologically significant coumarin derivatives. These include natural product analogues and highly emissive fluorescent probes for sensing and bioimaging applications. This review summarizes recent advances in lanthanide triflate-mediated strategies for coumarin synthesis, with highlighting on reaction scope, mechanistic insights, and emerging applications in medicinal and materials chemistry
Abstract: Organocatalysis is a well-known synthetic approach to chiral molecules that avoids the use of noxious metal catalysts, which are potential contaminants of the target compounds. Although many natural products (amino acids, alkaloids, sugars) have already been exploited as efficient organocatalysts, the iminosugars have been much less employed. The present review highlights the recent advances in this promising research field by describing the aldol and Mannich reactions, [3+2] and [4+2] (Diels-Alder) cycloadditions, and the multicomponent reactions catalysed by iminosugars (five-, six-, and seven-membered ring iminosugars as well as bicyclic and dimeric six-membered ring iminosugars). The review also includes a section dealing with the use of iminosugars and congeners as chiral ligands in asymmetric transition-metal catalysis. In addition to their catalytic properties, the preparations of these iminosugar derivatives and congeners are also detailed.
Chalcones are important scaffolds in medicinal chemistry due to their simple synthesis and diverse biological activities. This review summarizes the key synthetic approaches for chalcone preparation, including classical Claisen-Schmidt condensation, microwave-assisted, solvent-free, and modern coupling methods, along with their reported pharmacological properties. Literature findings reveal that chalcones exhibit significant antiprotozoal activity against Plasmodium, Leishmania, and Trypanosoma species, as well as notable antimicrobial, anti-inflammatory, anticancer, antioxidant, and anti-HIV effects. Structure-activity relationship studies indicate that specific aromatic substitutions and modifications of the α, β-unsaturated carbonyl system enhance biological activity. Overall, chalcones remain promising pharmacophores; however, further optimization of synthetic strategies and standardized biological evaluation are required to support their future development as therapeutic agents.
Abstract: Cynandione A (CA) is a natural bioactive polyphenol isolated from Cynanchum wilfordii, which has attracted considerable attention owing to its notable anti-inflammatory activity and multifunctional pharmacological potential. CA has been reported to exhibit immunomodulatory, neuroprotective, and hepatoprotective activities in various models. However, its limited natural abundance and structural complexity hinder extensive biological exploration. Consequently, the total synthesis of CA has been studied extensively. The first total synthesis of CA was reported in 2005, and the original six-step synthesis has evolved into more efficient approaches, including a scalable two-step synthesis and a recently developed one-pot method, which enable gram-scale production with high yield and operational simplicity. A key feature of these strategies is the regioselective conjugate addition of acetylphenol derivatives to an in situ-generated benzoquinone intermediate, governed by electronic and steric factors. This review outlines the synthetic evolution of CA and summarizes its pharmacological activities. The integration of advanced synthetic design with mechanistic pharmacology underscores the value of CA as a promising lead compound for further drug development. Continued optimization of its synthesis and biological validation will facilitate its translation into therapeutic applications.
In Figure 1, part ‘d’ was mistakenly labeled as ‘b’, which has now been corrected in the article entitled “α-Cyanostilbene Containing -NH2 Unit: Facile Preparation, Characterization, Solvatochromism, Acidichromism, Water Detection in Hygroscopic Organic Solvents”, published in Letters in Organic Chemistry, 2026, 23, 24-34 [1]. The original article can be found online at https://www.benthamscience.com/article/150073 We regret the error and apologize to readers.
Abstract: The escalating prevalence of antimicrobial resistance poses a severe global health threat, urging the scientific community to explore novel chemical entities with potent, broad-spectrum antimicrobial properties. Among various heterocyclic scaffolds, pyrazoline derivatives have attracted considerable interest due to their structural versatility and diverse pharmacological activities. This review systematically presents recent developments in the synthesis and structural-activity relationship (SAR) of pyrazoline-based compounds with proven antimicrobial efficacy. The synthesis of pyrazoline analogues primarily involves the cyclocondensation of chalcones with hydrazine derivatives, employing both conventional and modern techniques, such as microwave-assisted synthesis and green protocols. Structural modifications through the incorporation of various electronwithdrawing or electron-donating groups have been widely explored to enhance antimicrobial potential. Notably, substituents such as halogens, nitro, hydroxyl, methoxy, and alkyl chains have demonstrated significant influence on biological activity by improving cell permeability and interactions with microbial targets. Several derivatives show potent activity against both Gram-positive and Gram-negative bacteria, as well as fungi, often outperforming standard antimicrobial agents. Furthermore, SAR studies reveal that the position and nature of substituents on the aromatic ring play a crucial role in determining the selectivity and potency of the derivatives. This review provides valuable insights into how synthetic strategies and structural features influence antimicrobial activity, serving as a guide for rational design and optimization of future therapeutic agents. The findings reinforce the potential of pyrazoline scaffolds as a viable platform in combating microbial infections and multidrug-resistant organisms.
Abstract: Over the past decade, there has been remarkable progress in the production of physiologically significant and architecturally varied 2-amino-3-cyanopyridine derivatives, achieved through the adoption of green chemistry. The most recent developments in the environmentally friendly multicomponent green synthesis of 2-amino-3-cyanopyridine and its derivatives are highlighted in the current review. Significant advancements encompass the implementation of energy-efficient methods, including microwave and ultrasound-assisted synthesis, along with the implementation of benign catalysts, including carbocatalysts, transition metal catalysts, phase transfer catalysts, organocatalysts, photocatalysts, acidic nano catalysts, and biodegradable composites. Additionally, the review emphasizes the importance of solvent selection, especially the benefits of solvent-free circumstances and the application of water as a recuperative and non-poisonous medium. This study is a useful resource for academics dedicated to developing green chemical practices by synthesizing existing information and defining future research paths.
Abstract: Chiral succinimide derivatives are privileged scaffolds in bioactive compounds and pharmaceuticals. In this study, a novel class of bifunctional thiourea catalysts derived from isosteviol and a chiral 1,2-diphenylethylenediamine scaffold was synthesized and applied in the enantioselective Michael addition of aldehydes to maleimides. Under optimized conditions in CH₂Cl₂ at room temperature, a broad range of succinimide derivatives were obtained in high yields (82–97%) with excellent enantioselectivities (up to 99% ee). Both enantiomers of the adducts were accessible by switching between the two catalyst configurations. The substrate scope accommodated various N-aryl maleimides bearing electron-donating or electron-withdrawing groups, as well as alicyclic aldehydes. The reaction was scalable to gram level without loss of efficiency. A plausible enamine-based catalytic mechanism involving dual activation by the thiourea moiety is proposed. This protocol represents a significant advancement in the synthesis of chiral succinimides, offering a robust and scalable route to these valuable intermediates for drug discovery and expanding the utility of isosteviol-based organocatalysts.
Sulfines, a class of sulfur (IV)-containing heterocumulenes with the general structure X(Y)C=S=O, have attracted considerable interest due to their unique structural features and versatile reactivity in organic synthesis. This review provides a comprehensive overview of recent developments in sulfine chemistry from 2015 to the end of 2025. Significant progress has been made in synthetic methodologies, including the oxidation of thiocarbonyl compounds, base-induced eliminations, hetero-Wolff rearrangements of α-diazo sulfoxides, and other innovative approaches. These methods have enabled access to a wide range of sulfines with varying steric and electronic properties. In medicinal and natural product chemistry, sulfine intermediates have been identified in key biosynthetic pathways and bioactive molecule synthesis. Structural studies have elucidated intriguing aspects such as nonlinear geometry and stereoisomerism through advanced spectroscopic and computational analyses. Furthermore, sulfines have been served as valuable synthons in diverse transformations, including nucleophilic reactions and cycloadditions, leading to the construction of complex molecular architectures such as quinoxaline-2-thiols, quinoxalines, thiazoles, dithiohydantoins, and macrocyclic compounds. In conclusion, this survey underscores the growing importance of sulfines as powerful intermediates in organic synthesis and suggests future directions for research, including the development of catalytic asymmetric processes and the exploration of new applications in materials and pharmaceutical sciences.
According to the World Health Organization's (WHO) Regional Committee for Europe's 2013 European Mental Health Action Plan, Central nervous system disorders and mental illnesses are among the biggest public health concerns in terms of prevalence, burden of disease, and disability. The types of psychological disorders include anxiety, epilepsy, Parkinson’s disease, depression, schizophrenia, etc. The etiology of mental diseases is significantly influenced by disruptions in the equilibrium between neurotransmitters, primarily serotonin (5-HT), dopamine (DA), and noradrenaline (NA), as a result of advances in our understanding of brain processes. Multi-receptor ligands are synthesized as antipsychotic drugs that could play multiple roles in different mental illnesses. These ligands utilize a multiple-ligand strategy between serotonin (5-HT1A and 5-HT2A) and dopamine (D2) receptors to imply their pharmacological action. Piperazine derivatives are a significant class of bioactive substances, especially when it comes to treating mental health issues. These compounds are useful in the treatment of anxiety, depression, schizophrenia, and other CNS disorders because they can interact with a range of neurotransmitter systems. In this review, we have underlined the synthetic methods for piperazine and its derivatives, which include coupling reactions, Gabriel synthesis, catalytic synthesis, etc. This work also enumerated the molecular targets, which have been reported to be responsible for the biological activities of piperzines. Furthermore, this work also paves the way for further research, formulation, and development of more useful molecules.
Benzotriazole-mediated thiophene-3,4-imido-L-amino acid esters (L-phenylalanine methyl ester, L-tyrosine methyl ester, and L-aspartic acid methyl ester) were synthesised from thiophene-3,4- dicarboxylic acid via thiophene-3,4-anhydride to model the reactions of aromatic, phenolic, and polar amino acids, respectively. In synthetic studies, L-amino acids were first reacted with thiophene-3,4- anhydride to produce thiophene intermediates with a carboxylic acid group in the 3-position and an amide group in the 4-position. These intermediates' carboxylic acid functions were then activated using the N-acylbenzotriazole method. This resulted in an in situ cyclisation reaction that was distinct from conventional N-acylbenzotriazole reactions. This reaction formed the target products -thiophene- 3,4-imido-L-amino acid esters- in good yields. The electrochemical properties of the thiophene-3,4- imido amino acid ester derivatives, which are free from the 2,5-position of thiophene, were investigated. The structures of thiophene-3,4-imido amino acid esters were examined using 1H and 13C NMR spectroscopy.
In medicinal chemistry, the benzimidazole nucleus stands as a cornerstone, boasting remarkable pharmacological activities. Over the past century, the synthesis of benzimidazole and its derivatives, coupled with their diverse reactions, has paved the way for significant advancements in drug discovery and development. The unique potential of benzimidazole has attracted considerable interest from medicinal chemists, leading to the discovery of several clinically approved drugs that incorporate the benzimidazole core. Notably, a large number of patents have been granted for research about benzimidazole, underscoring its importance in pharmaceutical innovation. In recent years, there has been a notable surge in interest surrounding the biological applications of benzimidazole, which has doubled the attention it has garnered from researchers across various domains. This review highlights recent developments in the synthesis and structural modification of benzimidazole derivatives, with a focus on their antimicrobial, anticancer, anti-inflammatory, and antiviral properties. It also outlines the Structure-Activity Relationship (SAR) studies that have guided these developments, while discussing contemporary synthetic methodologies and green chemistry approaches used in their preparation. Furthermore, this manuscript explores potential molecular targets and mechanisms of action associated with benzimidazole-based compounds. By summarizing key trends and findings from the past decade, this work aims to provide researchers with insightful perspectives and future directions for the design and discovery of benzimidazole-based drugs. The study explores potential molecular targets and mechanisms of action associated with benzimidazole-based compounds. By summarizing key trends and findings from the past decade, this work aims to provide researchers with insightful perspectives and future directions for the design and discovery of benzimidazole-based drugs.
Over the past few decades, the Barton-Kellogg olefination reaction has emerged as a crucial C–C connective technique utilized in synthesizing overcrowded alkenes. The reaction has good stereoselectivity and has an enduring relevance due to the scope of its integration into complex molecule synthesis and material science applications. This review examines the developments in Barton- Kellogg olefination between 2021 and 2025, highlighting significant advances in mechanistic understanding, reaction conditions, substrate scope, and methodology. Recent developments, including the creation of asymmetric versions, gentler reaction protocols, and innovative catalyst systems, have enhanced the synthetic value of this reaction. Additionally, this review summarizes recent research on computational studies related to the mechanism and kinetics of the response, in relation to the present challenges and possible future paths for synthetic organic chemistry researchers.
