Letters in Organic Chemistry - Volume 22, Issue 1, 2025

In this study, we have developed an expeditious and efficient method for the synthesis of 2,4,5–triaryl imidazole derivatives using thiamine hydrochloride as a catalyst. The one-pot, solvent-free-multicomponent reaction of an aromatic/heterocyclic aldehyde with benzyl and ammonium acetate at reflux conditions leads to the formation of title compounds in extremely good yields. This protocol offers several features, such as safe, simple, atom efficient, economical, mild conditions, minimum waste, easy work-up procedures, shorter reaction time (40-45 min), catalyst recyclability, etc. The developed methodology is operationally simple and eco-friendly.

Many natural and synthetic steroidal compounds have been converted by biotransformation to get highly valuable products for pharmaceuticals or chemical intermediates for the production of drugs. This review summarizes the biotransformation of sixty-six steroids 1-66 (ten of pregnane 1-10, fifty of androstane 11-60 while six steroids of estrane series 61-66) by using different strains of Rhizopus arrhizus, a well-known fungus of the zygomycetes group, used in food, dairy, pharmaceutical and numerous biotechnological processes. R. arrhizus transformed only fifty-four compounds 1-51 and 61-63, whereas nine compounds of androstane 52-60 and three compounds of estrane series 64-66 remained unchanged. R. arrhizus brought various structural modifications in steroids, including hydroxylation, epoxidation, epoxide hydrolysis, reduction of double bonds and ketonic group, dechlorination and defluorination, deacetylation, oxidation of various functional groups and isomerization.

Oxadiazole is an organic compound featuring a heterocyclic ring housing carbon, oxygen, and nitrogen atoms. Due to their heightened stability in biological environments, oxadiazole rings exhibit significant biological activities, effectively addressing health challenges like infectious diseases and chronic conditions in medicinal chemistry. The main objective of this review is to discuss various synthetic approaches related to 1,3,4-oxadiazole and its derivatives. The diverse reactivity positions oxadiazole as a valuable building block in organic synthesis, with derivatives exhibiting promising pharmacological activities. It involves a systematic literature review, critical analysis, and synthesis of existing research. This review comprises the ever-expanding chemical knowledge and has significant implications for drug development. Synthetic approaches to synthesizing oxadiazole through different schemes and methods have been discussed thoroughly. This review also concisely associated the pharmacological activities of oxadiazole and its derivatives. This review highlights the importance of continued research into the structure-activity relationships of oxadiazole derivatives, paving the way for developing novel and more potent therapeutic agents.

Cancer is a global health issue, and cancer cells' resistance to existing treatments has prompted a search for new anticancer drugs. The DNA of cancer cells is regarded as the primary target for developing new molecules. In-silico studies aid in the optimization of current pharmacophores and the development of new molecules. This study aimed to optimize the pharmacophore utilizing QSAR studies and pharmacophore mapping to generate novel chemical entities (NCEs) of pyrimidine derivatives as DNA inhibitors for cancer treatment. Furthermore, these NCEs were subjected to molecular docking and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) screening to determine their drug-likeness. This study used Schrodinger's Maestro (13.4) software for pharmacophore mapping, QSAR, molecular docking, and ADME. Toxicity was determined using the Pro Tox II online tool. Pharmacophore mapping was performed using the phase module. The QSAR model was generated using an atom-based QSAR approach. The Qik prop module was utilized for ADME prediction. Molecular docking was done in Standard precision mode. In pharmacophore mapping, we discovered that the DHHRR_1 hypothesis fitted best, with a survival score of 5.4408. The optimal atom-based QSAR model produced correlation coefficients of R² = 0.9487 and Q² = 0.8361. Based on QSAR research, a new set of 43 derivatives was generated. These compounds pass all ADMET requirements. In molecular docking investigations, three compounds demonstrated binding with key amino acids with a significant dock score comparable to the standard. Considering docking data and pharmacokinetic behavior of newly developed compounds, molecules NC10, NC9, and NC43 have the highest DNA binding capability.

4-Hydroxyquinoline-2(1H)-ones exhibit multiple biological activities, and studying their synthetic methods is of great significance. In the presence of tetramethylguanidine and silver nitrate, 4-hydroxyquinoline-2(1H)-ones were efficiently synthesized from 2-ethynylanilines and carbon dioxide under atmospheric pressure. The reaction conditions, such as types of silver catalysts and reaction solvents, were optimized, and the applicability of the substrate was preliminarily investigated. This method provides an alternative pathway for the synthesis of 4-hydroxyquinoline-2(1H)-ones and the conversion and utilization of carbon dioxide.

β-(N-arylamino)acrylates are building blocks of great industrial interest as they allow the obtention of a variety of heterocyclic substances, such as quinoline and pyridone derivatives. Therefore, the development of new methodologies for the synthesis of these substances is still of interest. In this work, fourteen β-(N-arylamino)acrylates were synthesized in a multigram scale from the reaction of mono- and di-substituted anilines with diethyl ethoxymethylenemalonate by sonochemistry (US) and the results compared to those obtained by conventional heating. The use of the US brought many benefits to these syntheses, including faster reactions and increased yields. The crystal structure of diethyl 2-(((2-chloro-5-nitrophenyl)amino)methylene)malonate is also reported.

The synthesis of α,β-unsaturated compounds is crucial in organic chemistry, especially in drug discovery and pharmaceutical development. In this study, NCP@POCl2-x (Fe3O4@SiO2@chitosan@POCl2-x) has been introduced as a new, environmentally friendly, and highly efficient heterogeneous magnetic nanocatalyst for the synthesis of α,β-unsaturated carboxylic acids. This catalyst facilitates the in situ transformation of POCl2-x to PO(OH)2 in the presence of water, effectively converting β-hydroxy nitriles into α,β-unsaturated carboxylic acids through a specific mechanism involving water and heat. The reactions display notable regioselectivity, leading to high-purity products and quantitative yields. NCP@PO(OH)2 exhibits heterogeneity, magnetic properties, straightforward recovery, and outstanding performance, making it a valuable catalyst for efficient and selective transformations of β-hydroxy nitriles. Additionally, it can be easily separated from the mixture of reactions using external magnetic forces.

An organocatalytic, one-pot four-center two-component coupling reaction has been developed for the synthesis of tetrahydro-1H,7H-chromeno[3,4-c]chromen-1-one derivatives. The reaction proceeds smoothly in the presence of 5 mol% DL-Proline in methanol under reflux conditions. This method involves the Knoevenagel condensation of O-alkynyl tethered 2-hydroxybenzaldehydes with cyclic 1,3-diketones followed by an intramolecular hetero-Diels-Alder reaction. Novel classes of oxygen containing polycyclic frameworks are prepared in good yields by using this approach.