Letters in Organic Chemistry - Volume 22, Issue 9, 2025

Pyrazolidine-3,5-dione (PZD) derivatives have emerged as a class of compounds with notable pharmacological potential, drawing significant interest due to their broad range of therapeutic applications. This review consolidates data spanning from 1953 to 2004, providing a comprehensive overview of their synthesis, biological activities, and mechanisms of action while underscoring their diverse therapeutic promise. The synthesis of PZD derivatives has evolved with the use of advanced methodologies such as reactions with malonic acid, substituted hydrazines, benzothiazoles, and aryl aldehydes, along with modern techniques like microwave-assisted reactions and solid-phase synthesis, which enhance efficiency and promote structural diversity. These derivatives exhibit a wide array of pharmacological activities, including anti-inflammatory, analgesic, antipyretic, antimicrobial, anticancer, antidiabetic, and neuroprotective effects, highlighting their versatile therapeutic potential. Furthermore, PZD derivatives demonstrate efficacy as insecticides, miticides, and herbicides, suggesting their relevance in agricultural applications. The mechanisms of action behind their therapeutic effects include the inhibition of critical enzymes involved in amino acid biosynthesis and cell wall formation in microorganisms, as well as modulation of receptors, such as PPARγ and the Farnesoid X receptor. Several PZD derivatives also exhibit significant antimicrobial, antifungal, and antitubercular properties, positioning them as potential candidates for the treatment of bacterial and fungal infections. Additionally, some derivatives have shown promise as anticonvulsants, Dyrk1A inhibitors, and enhancers of Mycobacterium tuberculosis sensitivity to antimicrobials, demonstrating their broad therapeutic versatility. Despite the promising pharmacological activities, further research is required to optimize the pharmacokinetic profiles of PZD derivatives, minimize potential side effects, and expand their clinical applications. This work will be essential in advancing PZD derivatives as effective treatments for a range of diseases, making them valuable candidates for future drug development.

The present study aimed to determine the antioxidant potential and phytochemical components of aqueous extract of Matricaria recutita, which grows in hilly areas of Azad Kashmir, Pakistan. In order to evaluate its antioxidant activity, different methods, such as DPPH radical scavenging, ABTS scavenging, lipid peroxidation, and metal chelation assays, were performed. The flower extract showed higher DPPH radical scavenging activity (IC50: 75.3 µg/ml) compared to the leaf extract (IC50: 82.3 µg/ml). Similarly, the flower extract displayed higher ABTS radical scavenging activity (IC50: 102.3 µg/ml) compared to the leaf extract (IC50: 107.5 µg/ml). Significant metal chelating ability was observed of Matricaria recutita. There existed a significant correlation among the different antioxidant activities. Detailed phytochemical analysis of flower extracts showed the presence of important phenolic and flavonoid compounds, including gallic acid, chlorogenic acid, caffeic acid, qurecetin-3-galactoside, apigenin-7-glucoside, kaempferol-3-sinapoylsophotrioside, esculetin, kaempferol 3-(caffeoyldiglucoside)-7-rhamnoside, quercetin-3-sinapolysophoroside-7-glucoside, quercetin-3-(caffeoyl-diglucoside)-7-glucoside, isorhamnetin-3-(caffeoyldiglucoside)-7-rhamnoside, kaempferol-3 feruloylsophoroside-7-glucoside, kaempferol-3-malonylglucoside, quercetin-3-(6″-acetyl)glucosyl-2″-sinapic acid, 5, 7, 3′-trihydroxy-6, 4′, 5′-trimethoxyflavone, and tetrahydroxy-dimethoxyflavone. On the basis of these results, it has been concluded that Matricaria recutita collected from Azad Kashmir contains important phytochemicals and can be utilized as a source of antioxidants.

A new isochromanone, (3R,4R)-3,6,8-trihydroxy-3,4,5-trimethylisochroman-1-one (1), together with six known isochromanones (2-7) and one known isobenzofuranone (8), were obtained from the Arctic fungus Gyoerffyella sp. CPCC 401434. The chemical structures were determined on the basis of extensive NMR and MS data analyses. All the compounds were first reported from the genus Gyoerffyella. Compounds 6 and 7 showed significant cytotoxic activities. Compounds 2, 3, 5, 8, 9, and 11 displayed significant anti-IAV (H1N1) activities, similar to that of ribavirin.

Premna odorata is a plant species with various medicinal properties. However, in Central Vietnam, the seeds of this plant have not been previously studied for their chemical constituents. The aim of this study was to isolate and identify compounds from the seeds of P. odorata collected from Phu Yen province, Vietnam. The seeds were extracted using dichloromethane. The chemical constituents were isolated and purified. Their structures were elucidated through spectroscopic methods, including one-dimensional (1D) and two-dimensional (2D) Nuclear Magnetic Resonance (NMR) spectroscopy, mass spectrometry, and comparison with existing literature data. A new triterpenoid (1) and four known flavonoids: diosmetin (2), luteolin (3), acacetin (4), and apigenin (5), were successfully isolated from the dichloromethane extract of P. odorata seeds. The structures of these compounds were determined based on spectroscopic data. Compound 1 was also tested for cytotoxicity on the KB cell line, showing significant activity with an IC50 value of 40.98 μM. This study presents the first chemical investigation of the seeds of P. odorata. The identification of one new triterpenoid and four known flavonoids contributes to the understanding of the chemical composition of this plant and provides a basis for further pharmacological studies.

The production and consumption of biodiesel in Brazil and worldwide have considerably increased in the last decades. As a consequence, the waste glycerol (glycerin) as a byproduct from this synthetic process has also increased since approximately 10-30% of glycerol is generated in the biodiesel synthesis process. Therefore, the reuse of glycerol after the biodiesel synthesis is highly desired. However, waste glycerol purification is still a costly process. In this context, herein, we propose a synthetic alternative for the use of waste glycerol as a solvent and promoting medium for condensation reactions of 1,8-diaminonaphthalene and different aldehydes. The reactions were carried out using the waste glycerol without prior purification at room temperature for 30 min, affording the synthesis of a series of perimidines in excellent yields. Furthermore, a comparative study was performed between the use of commercial glycerol or waste glycerol in the reactions, and the results showed that the waste glycerol is more efficient considering the product yields. The use of waste glycerol as a green solvent and a promotion medium for organic processes is a robust, sustainable, and economically viable option for the application of this undesired byproduct of biodiesel synthesis.

In this work, novel bis(benzimidazole)amine, N-benzimidazole(benzothiazole)amine, and N-benzimidazole(benzoxazole)amine have been synthesized via a one-pot, intramolecular cyclization of 2-iodoaniline and 2-aminobenzimidazoles (thiazoles and oxazoles)-trichloroacetonitrile adduct using copper(I) iodide and DMF under ultrasound-assisted reaction with moderate to good yields. Using basic materials and simple and available reagents, gentle copper-catalyzed reaction conditions, easy purification with the help of solvent, good yields, non-addition of ligands, application of a simple and efficient sonochemical method, short reaction times, and the synthesis of 15 new heterocycle compounds have been appreciable features of this protocol.

Dibenzocarbazoles are a class of important materials used in optoelectronic devices. Their simple and practical construction, therefore, holds great potential from both academic and industrial application aspects. However, the conventional synthetic methods for these compounds often suffer the inadequacies, such as tedious synthetic processes, harsh reaction conditions, limited substrate scope, and high cost. Considering the advantage of the rapid development of photochemistry in organic synthesis, we report a concise and efficient synthetic method for these dibenzo[a,g]carbazole compounds under visible light irradiation. This new protocol enables the reaction to proceed under ambient temperature without any catalyst or metal additives, representing a highly efficient and cost-effective pattern. The results infer that the synthesis takes place via 6π electrocyclization and the consequent dehydrogenation in one pot under mild reaction conditions. Starting from the easily available β-tetralone and arylamine, a variety of substrates bearing diverse substituents are smoothly converted into the corresponding dibenzo[a,g]carbazoles with moderate to good yields. It is concluded that the electronic properties of the substituents could not exert a significant influence on the product yield, but the steric hindrance showed an obvious negative effect. This newly developed protocol features the easy availability of starting materials and high cost-efficiency, providing a good alternative for the efficient synthesis of dibenzocarbazoles and their derivatives.

An efficient and green method for the A³-coupling reaction of saliciladehyde, secondary amines, and terminal alkynes to synthesize propargylamines using a microwave reactor has been demonstrated. The synthesis showed several salient features, such as high yield of products, rapid product formation, and environmentally benign reaction conditions. Furthermore, the synthesis could be performed in gram scale. Nine propargylamine adducts were obtained in high yields and their structures were confirmed by NMR data. A plausible reaction mechanism was also suggested.