Current Organic Chemistry

New developments in the chemistry of quinoline derivatives are reviewed. Two general synthetic routes based on the utilization of mono-substituted or ortho-substituted anilines are discussed. Their major methods and modifications are analyzed. Keywords: quinolines, non-heterocyclic precursors, nucleophiiic nitrogen, synthesis, microwave, cyclizations

Aza-derivatives of phenols such as Schiff bases and hydrazones are an important and interesting group of chemical compounds. They exhibit a number of biological activities and play an important role in the regulation of many biochemical processes. Due to these properties, these compounds are potentialy useful for the design and production of novel anticancer, antimalaria, antivirus and antimicrobial drugs. The primary aim of the present review is to compare selected groups of phenol-derivatives containing azo-, heterocyclic, aromatic, alkyl and sugar moieties in view of their potential use and undesired effects, since some of them are widely used as dyes in the industry. Despite the vast number of azo derivatives of phenols which were synthesized and tested with respect to their biological activities, there is a continuous search for compounds of this group which might exhibit interesting, new biological effects. Keywords: Schiff Bases, Azo Derivatives, Phenols, biological activities, antimalaria, antimicrobial drugs

Bioconjugation is a burgeoning field of research. Novel methods for the mild and site-specific derivatization of proteins, DNA, RNA, and carbohydrates have been developed for applications such as ligand discovery, disease diagnosis, and high-throughput screening. These powerful methods owe their existence to the discovery of chemoselective reactions that enable bioconjugation under physiological conditions-a tremendous achievement of modern organic chemistry. Here, we review recent advances in bioconjugation chemistry. Additionally, we discuss the stability of bioconjugation linkages-an important but often overlooked aspect of the field. We anticipate that this information will help investigators choose optimal linkages for their applications. Moreover, we hope that the noted limitations of existing bioconjugation methods will provide inspiration to modern organic chemists.

Since the rediscovery of proline in 2000 as catalyst in aldol reaction by List, Barbas and Lerner and, soon after, the development of iminium catalysis by D. W. C. MacMillan, the emergence of organocatalysis as an important tool in organic synthesis is outstanding. During the last years, several research groups have worked in the development of new and powerful methodologies that allow us to build difficult molecules with high yields and enantioselectivities in a metal-free environment. Moreover, the possibility to join two or more organocatalytic reactions in one process has become one challenging goal for chemists, probably due to the costly protecting groups and time-consuming purification procedures after each synthetic step that are one of the common issues in organic synthesis. To circumvent these problems, tandem, domino, cascade or multicomponent organocatalytic reactions have been utilized for the efficient diastereo- and enantioselective construction of complex molecules from simple precursors in simple processes. For example, different tandem organocatalytic reactions such as cyclopropanation, aziridination, Michael-aldol, Michael-α-alkylation, etc. have been developed since 2006 with excellent yields and stereoselectivities. Herein, we describe the last trends and examples of organocatalytic domino reactions. This review aims to cover and discuss the current development of this fast growing field.

Pyrazoles are of considerable interest due to the broad variety of their biological activities. This overview summarizes structures of pharmacologically interesting pyrazoles, natural products, technically applied pyrazoles as well as pyrazole syntheses published during the last decade. In addition, new insights into the properties such as tautomerisms, conformations, pyrolyses and decomposition reactions of pyrazoles are reviewed. Keywords: Condensation, Diazo Compounds, 1,3-Dipolar Cycloaddition, Hydrazines, N-Heterocyclic Carbene, Natural Products, Rearrangement, Regiochemistry, hydroxyl function, pyrazole-trifluoroacetic acid clusters, Withasomnine, Withania somnifera (Solanaceae), methoxywithasomnine, Newbouldia laevis, Discopodium penniervium, Suberites vestigium, Elytraria acaulis

African plants have long been the source of important products with nutritional and therapeutical value. Coffee originates from Ethiopia, Strophanthus species are strong arrow poisons and supply cardenolides for use against cardiac insufficiency, the Catharanthus roseus alkaloids are well-known antileukaemic agents - just to mention a few examples. Research is continuing on the vegetable material from this continent in an endeavour to find new compounds of therapeutic interest. An outline is presented here covering the results obtained by the Institute of Pharmacognosy and Phytochemistry of the University of Lausanne during 15 years work on African plants. The strategy employed for the study of these plants is outlined, covering all aspects from the selection of plant material to the isolation of pure natural products. Different bioactivities have been investigated: the search for new antifungal, molluscicidal and larvicidal agents has been the most important axis. Results are also included for antibacterial, cytotoxicity, anti-inflammatory testing.

Palladium catalysed reactions serve as versatile tools in synthetic organic chemistry. By using these methodologies carbon monoxide can be introduced directly into a number of different sites in an organic molecule leading to the synthesis of carbonyl compounds and carboxylic acid derivatives. The substrate is reacted with a nucleophile such as an alcohol (alkoxycarbonylation), a primary or secondary amine (aminocarbonylation) or water (hydroxycarbonylation) or an organometallic reagent (formylation, crosscoupling reactions) in the presence of carbon monoxide and a palladium complex. Cyclocarbonylation, leading to a variety of heterocyclic compounds, can be regarded as a special type of the former reactions. Double carbonylation usually takes place at elevated CO pressures and produces α-ketoamides or -esters. Cascade reactions may be defined as multireaction ‘one-pot’ sequences in which the first reaction creates the functionality to trigger the second one. The use of two-phase processes makes catalyst recovery and recirculation, one of the greatest drawbacks of homogeneous catalytic processes, possible. As palladium-catalysed carbonylations usually tolerate a great variety of functional groups, they are attractive methods for the selective synthesis of intermediates of na tural or biologically active products. The reactions mentioned above can often be achieved in good yield and with high selectivity usually under very mild conditions. Because of the vast number of publications in this field, this review is dealing only with the conversion of organic halides and its contents is limited to the description of the most recent developments published until the end of 2001. Keywords: Palladium Catalysed, Carbonylation, Halides

The fixation of ligands onto molecules, surfaces and materials by use of reactions using a simple and unified chemistry is among the everlasting desires of chemists. Besides the general insensitivity with respect to the chemical structures of the ligand, the completeness of the reaction as well as the insensitivity from external reaction parameters (i.e.: solvents, ambient temperature) is wished. The copper(I)-catalysed azide/alkyne “click”-reaction (also termed Sharpless “click”-reaction, a variation of the Huisgen 1,3-dipolar cycloaddition reaction between terminal acetylenes and azides) is a recent re-discovery of a reaction fulfilling these requirements. Extremely high yields (usually above 95%) are combined with a high tolerance of functional groups and reactions running at moderate temperatures (25°C - 70 °C). The present review assembles recent literature for applications of these reactions in the field of material science, in particular on surfaces, polymers, and for the ligation of ligands to larger biomolecules, including own publications in this field. Since this is an extremely fast developing area, this review offers important knowledge to the interested reader. A number of > 64 references are included. Keywords: cycloaddition reaction, regioselectivity, Cu-acetylide, Sharpless-type-click-reaction, self assembled monolayers (SAMs)

Chitosan is a natural polymer composed of randomly distributed β-(1-4)-linked D-glucosamine (deacetylated unit) and Nacetyl- D-glucosamine (acetylated unit). It has been described as a non-toxic, biodegradable and biocompatible polymer with very interesting biological properties, such as permeation-enhancing and mucoadhesive properties, anticoagulant and antimicrobial activity and so on. Chitosan has been used in several areas such as biomedical, pharmaceutical and biotechnological fields as well as in the food industry. Recently, there has been a growing interest in the modification of chitosan to improve its solubility in physiological conditions, to introduce new applications or to improve chitosan biological properties. Research and development on a variety of amphiphilic copolymers containing hydrophobic and hydrophilic segments, have been very active due to their spontaneous self-assembly behaviour in aqueous media These smart transitions often lead to diverse functional compartment structures like micelles, vesicles and gels, which represent promising applications in the field of biotechnology and pharmaceutics. The aim of the present paper is to review the latest advances in the synthesis of chitosan amphiphilic derivatives with a special emphasis in their applications.

Isoxazoles are a class of heterocyclic compounds having a remarkable number of applications and have been demonstrated to be very versatile building blocks in organic synthesis. The wide range of biological activities includes pharmacological properties such as hypoglycemic, analgesic, antiinflammatory, anti-bacterial and HIV-inhibitory activity. Some isoxazole derivatives display agrochemical properties namely herbicidal and soil fungicidal activity and have applications as pesticides and insecticides. Isoxazoles have also been used as dyes, electric insulating oils, high temperature lubricants and polyisoxazoles have applications as semicondutors. The key feature of these heterocycles is that they possess the typical properties of an aromatic system but contain a weak nitrogen-oxygen bond which under certain reaction conditions, particularly in reducing or basic conditions, is a potential site of ring cleavage. Thus, isoxazoles are very useful intermediates since the ring system stability allows the manipulation of substituents to give functionally complex derivatives, yet it is easily cleaved when necessary. The ring opening provides difunctionalized compounds, namely 1,3-dicarbonyl, enaminoketone, γ-amino alcohol, α,β- unsaturated oxime, β-hydroxy nitrile or β-hydroxy ketone compounds, so that isoxazoles can be considered masked forms of these synthetic units. Consequently, isoxazoles have become an important synthetic tool. The construction of the isoxazole ring can be achieved by several synthetic approaches. However, the two major routes to isoxazoles are the 1,3-dipolar cycloadditon of alkenes and alkynes with nitrile oxides and the reaction of hydroxylamine with a three-carbon atom component, such as 1,3-diketone or an α,β-unsaturated ketone. This review aims to provide coverage of the recent developments on the synthesis and reactivity of isoxazoles. Keywords: cyclizationdehydration, cycloaddition, hydroxylamine, anti-inflammatory, boc-protected

Knoevenagel Condensation (KC) revolutionizes the classical carbon-carbon bond formation strategy by providing an adaptable and efficient route to generate C=C linkages from carbonyl compounds and active methylene substrates. Despite its synthetic versatility and wide applicability in the preparation of pharmaceuticals and functional materials, traditional methods have several drawbacks, including the use of harmful solvents, harsh reaction conditions, toxic catalysts or reagents, waste generation, lengthy and complex work-up, lower sustainability, and safety risks. These disadvantages emphasize the need to switch to more eco-friendly, efficient, and greener options. This review critically surveys advancements in green synthetic methodologies developed for the Knoevenagel condensation, focusing on innovations such as heterogeneous catalysis, ionic liquid-mediated systems, solvent-free conditions, microwave-assisted techniques, and the utilization of benign solvents like water and ethanol. A comparative discussion of these methodologies highlights their efficiency, product yields, reduced reaction times, and catalyst recyclability. Additionally, these green protocols typically do not require complex extraction or extensive work-up procedures to isolate the product, making the process simpler, cleaner, and more efficient compared to conventional methods. Furthermore, they offer greater environmental compatibility than the former strategies. Overall, this review emphasizes that green Knoevenagel protocols not only provide sustainable alternatives but also open new opportunities for the large-scale, environmentally friendly synthesis of valuable organic intermediates.

Abstract: Polyhydroquinolines (PHQs) are important nitrogen-containing heterocycles because of their wide range of pharmacological activities and potential for future pharmaceutical developments. The current review focuses on critically discussing recent advances in the green and sustainable multicomponent synthesis of PHQ derivatives. The scope includes energy-efficient approaches, such as microwave-, ultrasound-, and solarassisted synthesis, along with the implementation of sustainable catalysts such as organocatalysts, photocatalysts, nanocatalysts, transition-metal catalysts, and biodegradable composites for the synthesis of PHQ derivatives. Furthermore, the review highlights the importance of solvent selection, especially under neat conditions, and the use of green solvents as less-toxic, recyclable medium. The reviewed studies indicate that several advanced methodologies can reduce reaction time, improve synthetic efficiency, enable catalyst recycling, and minimise hazardous solvent use; however, limitations remain, including the use of expensive catalysts, a restricted substrate scope, challenges in catalyst separation, and scale-up, as well as specialised energy sources. Where available, green chemistry metrics including atom economy, E-factor, Process Mass Intensity (PMI), and Eco-Scale are evaluated to compare the environmental performance of reported methodologies beyond isolated yield. Overall, the review highlights recent progress towards PHQ synthesis, identifies gaps that limit the widespread use of pharmaceuticals and industrial applications, and suggests future research directions for scalable, economical, and reproducible synthetic methodologies.

Abstract: The synthesis of indole derivatives is of enormous significance in the fields of medical and synthetic organic chemistry. This is due to the fact that indole derivatives are frequently found in a wide variety of natural products and pharmaceuticals, as well as their vast biological activity. During the past few years, Fe-based NPs have gained recognition as catalysts that are not only efficient but also sustainable and cost-effective for the synthesis of indole frameworks. This approach offers a multitude of advantages, such as a wide catalyst surface area, the capability of being magnetically retrieved as a nanocatalyst, low toxicity, exceptional catalytic effectiveness, and mild reaction conditions. Fe-NPs have been successfully explored to create a wide variety of indole derivatives with high yields in a short duration. These transformations include Fischer indole synthesis, cyclization, and multicomponent processes. This review highlights the growing significance of Fe-based NPs as a nanocatalyst for indole synthesis.

Abstract: This review summarizes recent progress in transition-metal-catalyzed hydrogenation of esters to alcohols, focusing on both noble-metal and earth-abundant catalysts, with particular emphasis on pincer-type systems. It discusses how catalyst architecture and operating conditions govern performance, including chemoselectivity and, when applicable, enantioselectivity. Mechanistic insights, especially metal–ligand cooperation and bifunctional catalysis, are synthesized alongside related reduction strategies such as transfer hydrogenation. Despite notable advances, major challenges persist for non-precious catalysts, including insufficient activity/selectivity, limited mechanistic clarity, and constraints imposed by industrially relevant conditions. Future research should prioritize mild, lowtemperature/ low-pressure, alkaline-free processes and leverage computational approaches to accelerate catalyst design and broaden adoption in fine-chemical and pharmaceutical production.

Abstract: This review highlights the pyrimidine ring as a highly versatile and valuable core scaffold for the construction of fused azolo[d]pyrimidine systems, particularly pyrrolo[d]pyrimidines containing a single nitrogen atom within the azole ring (part-1). Fusion of a pyrrole moiety with the pyrimidine nucleus gives rise to structurally diverse regioisomeric frameworks, namely pyrrolo[2,3-d]pyrimidines (9-deazaguanines), pyrrolo[ 3,2-d]pyrimidines (7-deazapurines), and pyrrolo[3,4-d]pyrimidines, each exhibiting distinct structural characteristics and diverse biological profiles. Collectively, pyrrolo[d]pyrimidines have shown promising biological activities, including anticancer, antimicrobial, and anti-inflammatory effects, underscoring their importance in drug discovery. This review provides a comprehensive overview of their regioisomeric classification, synthetic approaches, recent methodological advances, and emerging biological significance, emphasizing their role as important scaffolds for future medicinal chemistry and pharmaceutical development.

Abstract: In 1820, P. J. Pelletier and J. B. Caventou isolated quinine, a naturally occurring alkaloid with pronounced antimalarial activity, from the bark of Cinchona spp.; at that time, its molecular structure remained undetermined. Fourteen years later, in 1834, F. F. Runge identified quinoline during the fractional distillation of coal tar, thereby introducing a heteroaromatic scaffold of considerable chemical and pharmacological relevance. The first formal synthesis of quinoline was reported in 1880 by Z. H. Skraup, who described the cyclocondensation of aniline with glycerol in the presence of concentrated H2SO4 and nitrobenzene - a transformation that subsequently became a fundamental methodology in heterocyclic chemistry. The total synthesis of quinine and elucidation of its molecular structure were achieved much later, in 1944, by R. B. Woodward and W. E. Doering. Over subsequent decades, extensive research has focused on developing alternative synthetic routes and optimizing reaction conditions to enhance yield, selectivity, and reproducibility, reflecting the enduring importance of quinoline and its derivatives. Quantum chemical studies based on density functional theory have provided valuable mechanistic insight into the Skraup-Doebner-Miller reaction. Analyses of natural charges and frontier molecular orbitals indicate that regioselectivity is governed by electronic asymmetry between competing electrophilic sites. This review summarizes recent advances in the synthesis of quinoline derivatives via the Skraup-Doebner-Miller reaction, with particular emphasis on mechanistic understanding, regioselectivity, and methodological developments, covering the literature up to 2025.

Graphitic Carbon Nitride (g-C3N4) is a versatile, metal-free compound with significant potential for sustainable organic synthesis. It has unique physicochemical properties including a nitrogen-rich structure, a tunable electronic bandgap, visible-light absorption, and robust thermal stability. Several g-C3N4-based composites have been developed to enhance their surface activity, charge-separation efficiency, and catalytic selectivity, including doped, mesoporous, metal-supported, and hybrid materials. This review highlights recent advances in the use of g-3N4-based composites as heterogeneous catalysts in key organic reactions, including oxidation, reduction, C-C and C-X bond-forming reactions, hydrogenation, and multicomponent processes. Special emphasis is placed on mechanistic considerations, structure-activity relationships, and the advantages of g-C3N4 as a sustainable alternative to traditional metal-based systems. Current challenges and future research directions are discussed to advance the development of next-generation g-C3N4-derived catalytic platforms.

Due to its prevalence in endogenous biomolecules, natural products, and clinically approved medications, indole, a flexible bicyclic heterocycle, has become a crucial scaffold in contemporary medicinal chemistry. Recent developments in the synthesis, design, and pharmacological assessment of indole derivatives in a variety of therapeutic domains are compiled in this review. Antiviral, anticancer, anti-inflammatory, antitubercular, antioxidant, antimicrobial, and anti-HIV properties are among their broad-spectrum biological effects that are emphasized. Strategic substitutions at positions 1-7 of the indole ring have a significant effect on bioactivity, pharmacokinetics, and target selectivity, according to insights from the structure-activity relationship (SAR). Furthermore, complex analogs can now be produced quickly and effectively using innovative synthetic techniques, such as the Fischer, Madelung, and Fischer indole syntheses. This thorough investigation addresses the current challenges and prospects for enhancing indole derivatives as multitarget drug candidates, while also highlighting their therapeutic value. To address unmet medical needs-particularly those related to resistance, chronic diseases, and the burden on the world's health-the work aims to support interdisciplinary research and rational drug design methodologies.

Abstract: Sharpless asymmetric epoxidation (SAE), a critical step in chemical synthesis, efficiently converts primary and secondary S alcohols into chiral 2,3-epoxyalcohols. This technique, which uses titanium tetraisopropoxide, diethyl tartrate, and tert-butyl hydroperoxide as an oxidant, typically produces remarkable enantiomeric excess, often exceeding 90%. Because of its dependability and high selectivity, SAE provides synthetic chemists with an important route to chiral intermediates, which are required for the production of both natural and therapeutic molecules. Because of their versatility, these epoxides are excellent building blocks for a wide range of complex molecular structures. One of SAE's distinguishing features is the precise stereochemical control provided by tartrate ligand selection. SAE is a feasible solution for industrial applications due to its adaptability in a variety of settings and ease of scaling up. Although some limitations on substrate range and sensitivity remain, continuing developments in catalyst design, combined with other asymmetric synthetic approaches, have considerably expanded the catalyst's selectivity and the range of functional groups that may be tolerated. Overall, Sharpless epoxidation confirms its status as an important technique in current organic chemistry for producing stereodefined, physiologically relevant compounds.

Abstract: This mini-review highlights the anticancer properties of hydroxy-substituted natural and synthetic flavonoids and their analogs. Natural and synthetic flavonoids have been reported. These compounds exhibit various biological activities, including anticancer. The role of hydroxy substituents located on ring A, B, or both rings of the flavonoid backbone has been underlined. The anticancer properties of 10 natural flavonoids are comprehensively described. The synthetic flavonoids involved in the potential treatment of leukaemia and hepatocellular carcinoma are also described.