Current Organic Chemistry - Volume 29, Issue 16, 2025

In the past decade, the field of ortho-quinone methides (o-QMs) has witnessed remarkable advancements, underscoring their pivotal role as synthetic intermediates in organic chemistry. These electrically neutral species, distinguished by a cyclohexadiene moiety conjugated with a carbonyl and an exo-methylene group, possess an aromatic zwitterionic resonance structure. This unique framework endows them with a pronounced electrophilicity, particularly at the 1,4-positions. The rich chemistry of o-QMs encompasses three principal reaction modalities: 1,4-conjugated addition, [4 + X] cycloaddition (X = 1, 2, 3, etc.), and oxa-6π-electrocyclization pathways. Specifically, the synthesis of chromane derivatives is achieved through [4 + 2] cycloaddition and subsequent oxa-6π-electrocyclization, whereas benzofuran derivatives are accessed via the [4 + 1] cycloaddition route. This review provides a systematic summary of the latest advancements in cycloaddition reactions involving ortho-quinone methides and their derivatives. It offers an in-depth analysis of the substrate diversity and potential reaction mechanisms underlying these transformations. The cycloaddition reactions presented herein are uniformly characterized as ionic systems, with the tautomerization between the oxygen anion generated subsequent to the deprotonation of o-QMs and the resulting carbonyl group identified as a pivotal step for reaction activation. Moreover, we have expanded on the discussion to include a detailed examination of drug intermediate compounds derived from o-QMs. These skeletal derivatives are highlighted for their growing utility in the realm of drug design and synthesis, effectively bridging the divide between foundational research and pharmaceutical applications. We aspire to stimulate the evolution and innovation of synthetic methodologies that leverage o-QMs as scaffolds. By in-depth investigation of the o-QMs-mediated cyclization reactions, we aim to offer theoretical insights that will guide the synthesis of intricate (chiral) cyclic compounds, thereby, enhancing the practical application of o-QMs in both chemical research and medical development.

Due to its unique features and environmental benefits, green synthesis is attracting researchers worldwide. To expand the uses of ionic liquids (ILs) in green chemistry, particularly as environmentally friendly solvents and catalysts, researchers are investigating novel methods to ILs and improving their characteristics. Due to its exceptional properties, ILs have been widely utilized as a green catalyst and solvent system in the synthesis of valuable heterocyclic compounds. Aza-heterocycle isatin derivatives are regarded for their versatility in drug development and medicinal research. Organic chemists have developed isatin-based frameworks employing ILs as solvents and catalysts aligning with one of the main goals of green synthesis, maximize synthetic efficiency while reducing environmental effects. This review provides a comprehensive summarization of reports related to the IL-assisted isatin derivative synthesis.

This review investigates the reactivity of cycloheptane-based β-ketoesters in producing α-functionalized derivatives. Cyclic β-ketoesters are a versatile chemical reagent that can react with suitable electrophiles to produce a variety of α-functionalized derivatives with excellent synthetic potential and promising biological properties. This review covers all reports on α-functionalization of cycloheptane-based β-ketoesters, including those demonstrating enantioselective synthesis using appropriate asymmetric catalysts. The review is divided into sections based on the α-center reaction. We also reviewed all available papers on the ring transformation of cycloheptane-based β-ketoesters, including their ring-opening and ring-expansion reactions. The mechanistic postulates of some complex procedures are highlighted.

Variously substituted benzothiazolamines were prepared and employed as starting material to synthesize some new benzothiazolamine-based bis-thiourea derivatives, such as 3, N3’-bis(6-substituted benzothiazolyl)terephthaloyl-bis(thioureas). Molecular modeling of all the synthesized compounds was carried out to check the interactions of all the bis-thiourea ligands inside the active pocket of enzyme 3MNG in comparison to competitive antioxidant inhibitor DTT (1,2-dithiane-4,5-diol). The antioxidant activities of all the synthesized compounds were determined using a DPPH radical assay performed by standard methods. Benzothiazole-based bis-thiourea derivatives exhibited significant potent antioxidant properties.

In the present study, an immobilization support, polyaniline tin oxide nanocomposite (PANI-SnO2-NC) was synthesized by in situ polymerization of aniline and ammonium peroxydisulphate. The prepared nanocomposite was characterized by various state-of-the-art techniques. The average size of native SnO2-NPs and PANI-SnO2-NC was 65±19 nm and 93±15 nm, respectively. An important industrial enzyme, α-amylase from Aspergillus oryzae was immobilized on PANI-SnO2-NC, which retained 87% enzyme activity. The improved stability of the immobilized enzyme was noticed against pH and temperature, as it retained 65% activity at 60°C while the free enzyme exhibited 41% activity under similar experimental conditions. Moreover, PANI-SnO2-NC-immobilized α-amylase produced starch (26.42 mg mL^-1) more efficiently than free enzyme (20.90 mg mL^-1) after 8 h in batch hydrolysis. PANI-SnO2-NC-bound α-amylase exhibited 54% activity after eight repeated uses. Molecular docking analysis of α-amylase with PANI suggested the ligand binding site to be located quite far away from the active site of the enzyme.

According to the PLOS Neglected Tropical Diseases Journal, infection caused by the Gram-negative bacterium Escherichia coli is a neglected tropical disease. Staphylococcus aureus is the most dangerous Gram-positive bacterium among staphylococcal bacteria. Moreover, resistance to Mycobacterium tuberculosis is an urgent public health issue. In this sense, cinnamic acid and acetamide derivatives have been used as strategic nuclei in the design of antimicrobial agents. With the aim of investigating whether antibacterial activity is improved with the junction of cinnamic and acetamide nuclei, cinnamic amidoesters were planned and evaluated as potential antibacterial agents. In silico (ADMET test and molecular docking) and in vitro (antibacterial and antituberculosis evaluation, and toxicity on Artemia salina larvae) studies were performed. Twelve cinnamic amidoesters were synthesized, which present positive characteristics for possible drug candidates, and showed subtle activity against E. coli, however, against S. aureus, unsubstituted and para-substituted compounds (R³ = H, Me, Cl, Br) showed significant activity, with MIC = 156.25-625 µg/mL^-1. Only one para-substituted compound (R³ = Bu) showed discrete activity against M. tuberculosis, with MIC = 200 µM. For the most active compounds against S. aureus, the molecular docking study demonstrated affinity with the TtRNA enzyme, which plays a central role in the assembly of amino acids into polypeptide chains. The most active compounds against S. aureus and M. tuberculosis were non-toxic on A. salina, with LC50 > 1000 µg/mL^-1. According to in silico/vitro studies, the non-toxic compound 5h (R³ = Cl) stands out as a potential antibacterial agent for further studies.