Letters in Organic Chemistry - Volume 19, Issue 11, 2022

A newly chiral tertiary amine-squaramide has successfully developed and applied into the asymmetric Michael addition of 4-hydroxycoumarin to β,γ-unsaturated α-ketoesters. The catalyst system performed well with a low catalyst loading of 1 mol% under mild reaction conditions. A series of coumarin derivatives were obtained with good yields and enantioselectivities.

A molecular iodine-catalyzed system for the decarboxylative substitution reactions of β-keto acids with N-benzylic sulfonamides via sp³ C-N bond cleavage has been disclosed. This procedure provides a series of α-functionalized ketones in good to excellent yields. Furthermore, the practicability of this method could be manifested efficiently in a gram-scale synthesis.

The novel coronavirus disease (COVID-19) emerged in December 2019. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is still existent all over the world. Researchers worldwide are continuously conducting in silico studies or virtual screening on various phytochemicals and reporting potential candidates that can be developed against COVID-19 after in vitro and in vivo validation. Antiviral effects of several phytochemicals have been demonstrated against different kinds of coronavirus, including SARS-CoV. Using drug repurposing techniques, a number of phytochemicals have shown substantial antiviral efficacy against COVID 19. This article reviews the efficacy of lead phytochemicals in computational studies on different important targets of SARS-CoV-2 like main protease, ACE-2, papain-like protease, spike protein, nsp-1, nsp-15, RdRp, MTase, helicase, cathepsin, TMPRSS-2. This review discusses potential application of these phytochemicals, which can guide medicinal chemists to choose phytochemicals to proceed with further in vitro and in vivo testing for SARS-CoV-2, which may eventually lead to an effective therapeutic agent and thus can be used to control the current ongoing pandemic.

In recent years, free radicals and oxidative stress are associated with aging, cancer, atherosclerosis, neurodegenerative disorders, diabetes, and inflammatory diseases. Confirming the role of oxidants in numerous pathological situations, including cancer, developing antioxidants as therapeutic platforms are needed. It has been well established that melatonin and its derived metabolites function as endogenous free-radical scavengers and broad-spectrum antioxidants. To achieve this function, melatonin can directly detoxify reactive oxygen and reactive nitrogen species and indirectly overexpress antioxidant enzymes while suppressing the activity of pro-oxidant enzymes. Many investigations have also confirmed the role of melatonin and its derivatives in different physiological processes and therapeutic functions, such as controlling the circadian rhythm and immune functions. This review aimed to focus on melatonin as a beneficial agent for the stimulation of antioxidant enzymes and inhibition of lipid peroxidation and to evaluate its contribution to protection against oxidative damages. In addition, the clinical application of melatonin in several diseases is discussed. Finally, the safety and efficacy of melatonin in clinical backgrounds are also reviewed.

The preparation of 6-chloro-5-nitrothieno[3,2-e][1,3]thiazin-4-one incorporating 2-(Nmorpholinyl) moiety is achieved via a conventional route. Interaction of the latter substrate with a set of N'-(aryl) benzothiohydrazides 1a-f, in the presence of triethylamine, led to a thiophene ring-opening process with the consequent generation of the respective thiolate salts 8a-f. Alkylation of the latter, using methyl iodide or allyl chloride, generated the respective novel 1,3,4-thiadiazoline-6-sulfanyl-1,3- thiazin-4-one hybrids, the structures of which were verified by HRMS and NMR spectral data.

In the present study, the SrCO³@montmorillonite nanocomposite was synthesized by loading Sr(NO3)2 on natural bentonite using a controlled and facile microwave method. The SrCO³@montmorillonite nanoparticles’ characteristics are identified using advanced techniques, such as infrared spectroscopy (IR), energy-dispersive X-ray analysis (EDX), X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), and pore size distribution analysis. Crossed-aldol condensation of an aromatic aldehyde with cycloalkanone in the presence of these nanoparticles produced α, α-bis(substituted-benzylidene) cycloalkanones in good yields without using any solvent. The present method is operationally simple and dose not use organic solvent, which makes the process environmentally benign.

A combinatorial library of pyrimidine hybrids based on 4H-chromene and 4H-pyran privileged structures has been developed by reacting phenyl isothiocyanate with chromene derivatives 1a-j and pyranopyrazoles 2a-f in refluxing dry pyridine, respectively. Thus, the target pyrimidine hybrids 3a-j and 4a-f were obtained in good yields with a simple reaction strategy.

Ag-TiO2 nanocomposite is reported to be an efficient, active, and benign recyclable catalyst for highly efficient synthesis of 1,8-dioxodecahydroacridine derivatives from dimedone, aromatic aldehydes, and several anilines or ammonium acetate in ethanol as a solvent at room temperature in a short reaction time and suitable yield. This catalyst is effortlessly recycled by simple filtration and can be reused up to five times with only a negligible loss in its catalytic effectiveness. Low catalyst loading, cost-effectively mild conditions, non-chromatographic purification of target compounds, excellent atom economy, informal procedure, use of a cheaply accessible nanocomposite catalyst, and recyclability of the catalyst are all significant benefits of this method. AFM analysis is performed to confirm the structure, topography, and morphology of Ag-TiO2 nanocomposite. 1,8-dioxodecahydroacridine derivatives having natural significance possess a wide range of pharmacological activities; for instance, antibacterial, antimalarial, anticancer, and mutagenic properties. In terms of the distinctions between aldehydes and anilines, this approach offers a wide range of applications.

This paper aimed at investigating the reaction of some acyl hydrazides with different terminal dibromoalkanes. This investigation revealed that acyl hydrazide by reacting with 1,4 and 1,5- dibromoalkanes in the presence of DABCO (1,4-diazabicyclo[2.2.2]octane) and TBAB (tetrabutylammonium bromide) underwent a facile intramolecular N2-double-alkylation to form pyrrolidine and piperidine ring derivatives under solvent-free conditions. Moreover, the alkylation of acyl hydrazide with 1,6-dibromohexane as a substrate produced the related N2-mono-alkylated derivatives under the same conditions. Interestingly, using K2CO3as the base in this reaction for 1,6-dibromohexane led to acyl hydrazide containing an azepane ring. Surprisingly, direct alkylation of 4-nitrobenzohydrazide with 1,2-dibromoethane led to an oxadiazine ring derivative. The product yield was found to be 60- 85% in 6-12 h.

New ruthenium complexes bearing bipyridine ligands with different substituents (propyl, hexyl, isobutyl, and benzyl) were synthesized and characterized by MS, NMR, FTIR, and UV/Visible spectroscopy. Moreover, their cytotoxic, anti-carcinogenic, and anti-biofilm activities were evaluated. The electrochemical properties of the complexes have been investigated by cyclic voltammetry. The HOMO and LUMO energy levels of RuL1-RuL4 were found to be (-5.45 eV)-(-5.46 eV) and (-2.98 eV)-(-3.01 eV), respectively. Cytotoxic activities of ruthenium complexes were investigated in Caco-2, HepG2, and HEK293 cells. It was found that RuL3 showed a cytotoxic effect on cancer cells without affecting non-cancerous cells at applied doses. The presence of the benzyl group may increase the cytotoxic effect of RuL3 compared to other derivatives that contain the alkyl group. The apoptotic effect of the RuL3 derivative was determined by using Arthur image-based cytometer. It found that RuL3 induced apoptosis in Caco-2 (5-fold) and HepG2 (2-fold) cancer cells, respectively. All ruthenium complexes inhibited Staphylococcus aureus ATCC 29213 biofilm, but RuL3 had a more pronounced effect. Moreover, RuL3 had biofilm inhibition and biofilm degradation effect, while RuL1 and RuL4 demonstrated only biofilm inhibition. The fluorescent microscopy analysis confirmed the antibiofilm effect of ruthenium complexes. All of these results clearly showed that RuL3 showed cytotoxic and apoptotic effects on cancer cells.

Esterification of higher free fatty acids content by using a photo-catalyst has recently been proved as the most efficient method for the pretreatment of non-edible oil to synthesize biodiesel. Methods: In the current study, mechanistic details of photo-catalyzed esterification reaction for four different fatty acids through density functional theory (DFT) calculations are explored and compared with un-catalyzed esterification reaction. Results: Revealed that the presence of photo-catalyst lowers the activation barrier and the structure of fatty acid has no significant effect on its reactivity. Thermodynamic data also revealed that the presence of photo-catalyst lowered the activation energy from 51.67 kcal/mol to 0.7495 kcal/mol. Furthermore, Gibbs free energy changes (ΔrGm and molar enthalpy changes (ΔrGm of the photo-catalyzed esterification reaction are negative, indicating that it is a spontaneous exothermic reaction. On the other hand, free fatty acids esterification in the absence of a catalyst is a kinetically unfavorable process with positive values of ΔrGmand ΔrHm Conclusion: Our findings theoretically clarify the mechanism of the photo-catalyzed esterification reaction of FFA present in non-edible oil, which facilitates the process of biodiesel production.

In the current work, the adsorption of cytophosphane (cytophosphane is a chemotherapeutic drug and is used to treat several specific autoimmune diseases and malignant processes) on the (5,5) SWCNT was studied using density functional theory (DFT) calculations in terms of geometry, energy gap, charge transfer, molecular electrostatic potential surface, and density of state analysis. The behavior of the binding properties and the electronic structures revealed that the cytophosphane molecule could be adsorbed on the SWCNT by the adsorption energy of approximately -100.3 kcal mol^-1. Also, it was found that the electronic properties of the SWCNT are very sensitive to the presence of cytophosphane molecules so the energy gap of the nanotube is changed by about 61% after the adsorption process. Based on calculated results, the SWCNT is expected to be suitable as a drug carrier for delivering cytophosphane drugs.

A novel tertiary amine squaramide has been successfully developed and applied to catalyze the asymmetric Michael addition between cyclic diketones and β,γ-unsaturated α-ketoesters. The catalyst system performed well with a low catalyst loading of 1 mol% under mild reaction conditions. A series of synthetically and pharmaceutically useful chiral bicyclic compounds were obtained with both high yields (up to 97%) and excellent enantioselectivities (up to 97% ee).