Letters in Organic Chemistry - Volume 22, Issue 3, 2025

The main aim of the present work was to conduct the one-pot microwave-assisted green synthesis of benzil and its derivatives. Benzil is acknowledged as a pivotal scaffold in the realm of medicinal and organic chemistry, owing to its extensive utilities. Due to the various merits of the green technology approach compared to classical methodology and the provision of sustainable chemistry, this reaction has received renewed interest for preparing benzil derivatives in an environmentally friendly manner with improved yields. We have, herein, presented a highly efficient route for the synthesis of benzil derivatives utilizing acetophenone and benzene derivatives as primary substrates. Notably, this synthesis obviates the necessity for any potentially hazardous catalyst and employs microwave irradiation and iodine green oxidant to facilitate the reaction. All synthesized compounds were characterized by spectroscopic techniques, such as IR, 1H NMR, and mass spectrometry. A green and efficient microwave-assisted synthesis methodology for benzil and its derivatives has been developed using iodine green oxidant. This approach has yielded the desired benzil derivatives with remarkable efficiency, achieving yields ranging from 91% to 97% within a short time of 10-15 minutes; the derivatives have been characterized using spectral techniques, viz., IR, ¹H NMR, and mass spectrometry. It is noteworthy that the entire reaction optimization process has been conducted in an environmentally friendly manner, thereby exemplifying a synthetic methodology being both environmentally sustainable and economically viable, compared to conventional techniques.

HSP90 assists as a crucial molecular chaperone that responds to environmental stressors and helps in the survival of cells in microorganisms. This protein is integral to the stress response, aiding in the stabilization of various proteins essential for microbial survival. Consequently, the ability of a number of tissues to adjust to endogenous stress depends critically on appropriate chaperone activity. Modulators of chaperone activity, however, have emerged as a novel and developing area of drug discovery due to the association between changed chaperone function and the development of numerous illnesses. Inhibition of HSP90alpha can disrupt proper protein folding, thus impairing growth and virulence in fungi. In this work, we selected novel leads of gallic acid derivatives with the help of OSIRIS Property Explorer and DruLiTo software. Selected leads were subjected to ADME-T studies for further screening. Docking and molecular simulation studies on selected compounds were performed using Schrodinger v21 and GROMACS software to predict the bioactivity of novel leads of 3,4,5 trihydroxy benzoic acid for suppression of the HSP90alpha enzyme. Compounds 4N, 18N, 15N, and 14N showed good docking scores of -6.5, -6.4, -5.91, and -5.98, respectively, which was comparable to standard ciprofloxacin. Compound 4N and compound 14N demonstrated notable binding interactions and were selected for further investigation through molecular dynamics studies with HSP90alpha (PDB ID: 1YC1). RMSD, H BOND, and RMSF analysis confirmed the stable binding of compounds 4N and 14 N with the HSP90 enzyme. The RMSF plot showed less than 0.35 nm fluctuation for the HSP90alpha enzyme in complex with different ligands. It can be concluded that ligand binding can cause stability to the conformation of the protein. Compounds 4N and 14N are considered to be the best theoretical lead, which can further be studied experimentally as HSP90 alpha inhibitors for antimicrobial activity.

The amide group is one of the most ubiquitous chemical motifs in the pharmaceutical field. An efficient continuous flow synthesis of amides was achieved by coupling acids with amines using 2-bromo-1-ethylpyridinium tetrafluoroborate (BEP) in the bio-derived “green” solvent γ-valerolactone (GVL). The reaction proceeded under mild reaction conditions (ambient temperature, 1 min) with simple filtration without the need for extensive purification, allowing a safe and on-demand generation of procainamide and VH032-Boc with a productivity of 0.44 g day^-1 and 0.99 g day^-1. The finding of our work aligned with green chemistry principles should result in its adoption by the chemistry community.

The objective of the study was to develop new Oxadiazole compounds using docking simulation studies for inhibitory action against the Cycloxoygenase-2(COX-2) enzyme. The study aimed at the development and identification of novel and potent derivatives of 1,3,4-oxadiazole for targeting anti-inflammatory disease by screening their inhibitory action against COX-2 enzyme with schrodinger molecular docking software and molecular simulation by GROMACS 2022. A library of 375 novel compounds of 1,3,4-oxadiazoles derivatives was designed and proposed for docking against cyclooxygenase-2 enzyme (COX-2)PDB ID: 6BL4, which was downloaded from protein data bank site https://www.rcsb.org/. MD simulations for three models were performed, namely, compound A-Cox-2, E-Cox-2, and G-Cox-2, for 100 ns. Out of 375 proposed compounds, the top 16 compounds with good docking scores and binding energy were selected for further ADME profile studies in which all compounds showed good results as compared to Standard drugs. RMSD values of 0.2 nm showed that all ligand-Cox-2 complexes were stable during simulation. Compound G was the most efficient in decent interactions with the residues ARG120 and TYR355 of cyclooxygenase-2, which were stable for 29.32, 21.52, and 12.00% duration of simulation along with comparatively better h-bond contacts. All potential inhibitors met Lipinski's rule of five, indicating oral availability. The potential compounds may be further evaluated for pharmacological activities using different in vitro and in vivo evaluations.

In the current study, we reported a cost-effective, simple strategy for the synthesis and reactivity of a novel series of chromenopyridine derivatives involving 2,4-diamino-3-carbonitrile moieties. These new compounds were synthesized in good yields from malononitrile and various chromene derivatives as a precursor, which was prepared by the reduction of iminocoumarin derivatives. The formed iminocoumarin was obtained by Knoevenagel condensation from malononitrile and different aromatic aldehydes. These novel chromenopyridine derivatives were further reacted with triethyl orthoformate under microwave irradiation to afford the final compounds, namely “chromenopyridine formimidate.” The structures of all molecules were characterized by FT-IR, ¹H NMR, ¹³C NMR, and elemental analysis.

Tulsion^®-8052 MP cation resin catalyst accelerates chemical reaction by creating a suitable environment for the aldehyde and indole reactants to interact and form desired product bis(indolyl) methanes in solvent-free room temperature conditions. The uniqueness of this catalytic method is that it is eco-friendly, recyclable, selective, and operates on a variety of functional groups with good to excellent yield at room temperature conditions without the use of any hazardous solvents, high temperature, and inert atmosphere.

This work is devoted to the synthesis of divers Michael adducts from (E)-α-atlantone as an α,β-unsaturated ketone isolated from Cedrus atlantica essential oil. The (E)-α-atlantone is subjected to ethyl cyanoacetate, phenylmagnesium bromide, and ethanol to produce the corresponding 1,4-Michael adducts in good yields. The conjugate addition of the appropriate reagents onto (E)-α-atlantone proceeds in a regiospecific manner, closely governed by the nucleophilicity of the reagents as well as their stereospecific blocking. The structure of the obtained Michael adducts is established using NMR (¹H & ¹³C) spectroscopy and elemental analysis. Likewise, the DFT method was utilized to comprehend the molecular properties, stability, and reactivity of the investigated compounds, as well as to explain the proposed mechanism. The computed outcomes are in good agreement with the experimental data.

Betulinic acid and its various synthetic derivatives have been reported to possess diverse biological activities and some of these may serve as useful therapeutic agents for a variety of human disorders. In this perspective, we have now developed convenient one-pot syntheses of new C-28 esters (2-7) of betulinic acid by esterification of the carboxylic moiety of betulinic acid (1) with various alkylating agents. All the target compounds were subjected to enzyme inhibition studies to ascertain their possible therapeutic utility. Compound 5 showed very potent lipoxygenase inhibitory activity with an IC50 value of 13.2 µM, being much lower than the IC50 value of 22.4 µM of baicalein, which was used as the standard. Butulinic acid itself and compound 6 also showed significant inhibitory potential (IC50: 32.4 and 25.1 µM) against the same enzyme. The activities of both compounds 5 and 6 have been justified by intensive docking studies. Compounds 2 and 3 exhibited substantial inhibition (IC50: 18.4 and 21.5 µM) against the enzyme butrylcholinesterase, compared to serine used as the standard (IC50: 7.8 µM).