Current organic synthesis最新文献

Carbodiimides (R-N=C=N-R) are well-known intermediates for the preparation of a variety of N-containing compounds, including heterocycles and amide linkages. Because of their high reactivity and easy availability, carbodiimides have been broadly used as building blocks in the synthesis of structurally complex and diverse heterocyclic compounds in multi-component reactions (MCRs). Recent advances in diversity-oriented synthesis with carbodiimide-based MCRs are discussed in this minireview and are classified into different sections based on the key transformation involved in the reactions, such as heteroannulation and nucleophilic addition reactions which containing metal-catalyzed reactions, multi-component reactions, and catalyst-free reactions subsections.

Aims and objectives: It is well established that 4H-pyran derivatives hold a significant position in synthetic organic chemistry due to their diverse biological and pharmacological properties. This work aims to introduce a novel synthetic pathway for highly functionalized 4H-pyran derivatives, achieved through a 1,4-Michael addition followed by a cascade cyclization. This reaction is catalyzed by LiOH·H₂O under ultrasonic irradiation in water, offering an efficient and environmentally friendly approach.

Materials and methods: In this study, lithium hydroxide monohydrate (LiOH·H2O) was used as the catalyst. To explore environmentally friendly methods, two novel approaches utilizing pure water were investigated (Method 1 and Method 2). The first method involves the use of alkylidene reagents malononitrile and ethyl acetoacetate in an aqueous medium. The second method features a multi-component cyclocondensation of aromatic aldehydes, malononitrile, and ethyl acetoacetate, activated by ultrasound waves and conducted in pure water. The impact of various substituents on the formation of 4H-pyrans, including both electron-poor and electron-rich aromatic aldehydes, was also evaluated.

Results: Most products were obtained in high yield and as very pure crystals with distinct colors. Generally, aromatic aldehydes with electron-withdrawing groups (Cl) exhibited greater reactivity than those with electron-donating groups (OMe). This trend is clearly demonstrated when comparing entries 3 and 4 with entries 5 and 6 in Tables.

Conclusion: Compared to other procedures, this method is simple, fast, eco-compatible since it uses water as a solvent. In addition, the products are obtained in good yields in the pure state after simple recrystallization without the need for other purification techniques, such as column chromatography. These factors make this novel approach highly attractive for the synthesis of 4H-pyrans.

Background: Sodalite is a type of zeolite with an intricate structure comprising a system of interrelated cages and tunnels. It is extensively used in sieving applications due to its unique structure and properties. As a result, it finds several uses in water and air purification, radioactive decontamination, detergents, and so on. Due to the potential positive environmental impact of sodalite materials, analysing the molecule at a structural level becomes the need of the hour.

Methods: Molecular descriptors form the basis of many convenient and cost-effective techniques for studying molecular structures. In this article, the neighbourhood sum-based descriptors are computed edge-partition techniques, simplifying the intricate structures with cages and tunnels into more simple graphs for mathematical convenience.

Results: This article presents the calculated analytical expressions for molecular descriptors, specifically focusing on various neighbourhood sum degree-based indices in sodalite structures.

Conclusion: The results presented in this article establish the dependence of the physical properties of a molecule on its underlying structure using the computed molecular descriptors. The graphical comparison of the results provides a visual representation of the behaviour of indices with respect to the molecular structure.

Derivatives of pyrimidinone, dihydropyrimidinone, and 2,4-diaryl-substituted pyrimidines were synthesized by cyclocondensation of α-aminoamidines with various saturated carbonyl derivatives and their analogs. The therapeutic potential of the newly synthesized derivatives for cancer treatment was evaluated using molecular docking calculations. The molecular docking results indicate that some of the synthesized diaryl derivatives of pyrimidine exhibit high binding affinity towards PIK3γ.

Aims and objectives: 4,6-Diaryl-substituted pyrimidines have shown high inhibitory potency against phosphoinositide 3-kinases (PI3Ks), which are important targets in oncology. Inhibition of PI3Ks could potentially be a viable therapy for human cancers.

Materials and methods: The synthesis of pyrimidinone and dihydropyrimidinone derivatives as well as a series of 2,4-diaryl-substituted pyrimidines were described. These compounds were synthesized by cyclocondensation of α-aminoamidines with various saturated carbonyl derivatives and their analogs.

Results: Derivatives of pyrimidinone, dihydropyrimidinone, and 2,4-diaryl-substituted pyrimidines were synthesized by combining α-aminoamidines with various saturated carbonyl derivatives and their analogs. By adjusting the large substituents in the 2-position, we gained the ability to modify the therapeutic properties of the resulting compounds. The potential of the newly synthesized derivatives for cancer treatment was assessed using molecular docking calculations. The results of the docking calculations suggest that some of the synthesized diaryl derivatives of pyrimidine have a strong binding affinity towards PIK3γ, making them promising candidates for the development of new anticancer medications.

Conclusion: We synthesized some pyrimidinones, dihydropyrimidinones, and 2,4-diarylsubstituted pyrimidines by combining α-aminoamidines with various saturated carbonyl derivatives and similar compounds. Molecular docking results suggest that certain diaryl derivatives of pyrimidine have a strong binding affinity for PIK3γ. Moreover, diphenyl derivatives of pyrimidine exhibited dual inhibitory activity against PI3K and tubulin, showing promise for the development of next-generation microtubule-targeting agents for use in combination therapies.

Introduction: The origin, synthesis, characterization and docking studies of (Z)-7- ((1R,2R,3R,5S)-3,5-dihydroxy-2-((R,1E,4E)-3-hydroxy-5-phenylpenta-1,4-dien-1- yl)cyclopentyl)-N-ethylhept-5-enamide, an impurity generated in the preparation of an antiglaucoma agent-Bimatoprost has been described.

Methods: This impurity was controlled by employing 30% Pd/C, and the impurity level was brought to the permissible level, i.e., 0.03% (ICH guidelines) in the final drug preparation of Bimatoprost.

Results: Finally, induced-fit docking calculations were performed to theoretically evaluate the binding efficiencies of these inhibitors in the crystal structure of Prostaglandin F synthase (PGFS).

Conclusion: There are negligible differences in RMSD and docking scores between the two ligands, which amount to only 0.18 Å and 0.313 kcal/mol, respectively. These findings strongly indicate that both ligands are likely to exhibit similar biological functions and efficiencies.

Background: In China, the traditional method for analyzing soil available phosphorus is inadequate for large-scale soil assessment and nationwide soil formulation demands. To address this, we propose a rapid and reliable method for soil-available phosphorus detection. The setup includes an on-site rapid pre-treatment device, a non-contact conductivity detection device, and a capillary electrophoresis buffer solution system composed of glacial acetic acid and hydroxypropyl-β-cyclodextrin.

Methods: The on-site rapid pre-treatment process includes fresh soil moisture content detection (moisture rapid detector), weighing (handheld weighing meter), stirring (handheld rapid stirrer), and filtration (soil rapid filter) to obtain the liquid sample, and direct injection (capillary electrophoresis detector). The phosphate ion detection parameters include capillary size, separation voltage, injection parameters, and electric injection. We used Liaoning brown soil, Henan yellow tidal soil, Heilongjiang black soil, and Anhui tidal soil as standard samples. Additionally, we used mathematical modeling methods and machine learning algorithms to analyze and process research data.

Results and conclusion: Following calibration with standard samples, the experimental blind test samples demonstrated conformity with the national standard method, exhibiting a relative standard deviation of less than 3%. The proposed pre-treatment device and non-contact conductivity detector are powered by lithium-ion batteries, rendering them ideal for extended field operations. The non-contact conductivity detector obviates the need for direct contact with test samples, mitigating environmental pollution. Furthermore, the neural network model exhibited the highest level of goodness of fit in chemical data analysis.

Introduction: The protection of the hydroxyl group as formamides is a crucial initial step in pharmaceutical synthesis.

Methods: In this study, we investigated the O-formylation of alcohols using dimethylformamide (DMF) in a mixture with a new magnetic nanocomposite Fe₃O₄@Chitosan/POCl_2-x.

Results: The results demonstrate that this core-shell heterogeneous nanocomposite facilitates the formation of alkylformate, yielding products with high efficiency ranging from 79% to 96% within a remarkably short reaction time of 1 to 12 hours at room temperature, depending on the substrate structure. Significantly, the presence of this nanocomposite exhibits remarkable selectivity, favoring the formylation of less hindered benzylic and aliphatic primary alcohols. However, bulkier alcohols and phenols exhibit lower reactivity under these conditions and thiols do not react. The simplicity of the work-up procedure, combined with the magnetic recyclability, makes it reusable and environmentally friendly.

Conclusion: This study highlights the efficacy of this novel magnetic nanocomposite in facilitating formylation reactions, emphasizing its potential for application in pharmaceutical synthesis and bio compounds. This is due to its attributes of non-toxic nature, stability, and significant advantages over conventional methodologies.

Background: New benzazacamalexin-related analogues are synthesized in an easily accessible one-pot approach. The method is based on the reaction of indoles with in situ formed electrophilic N-alkoxycarbonylbenzimidazolium reagents. For the first time, their application for N-alkylation of the indole nitrogen atom is announced toward novel trisheterocyclic hybrids. The structure of newly obtained products was spectrally characterized by 1D and 2D-NMR, FTIR and HRMS spectral data. The current scientific research is based on the application of a convenient and efficient route for the preparation of various benzimidazoles. This approach is both straightforward and economical, utilizing readily accessible and affordable reagents leading to target compounds.

Objective: The synthesis of novel benzimidazole-indole molecular hybrids as benzazacamalexin related analogues.

Methods: A suitable in situ method has been successfully applied, using an α-amidoalkylation reaction of indoles with N,N-diacyliminium reagents derived from benzimidazoles and alkyl chloroformates.

Results: The reactions led to the obtaining of ten novel compounds (5a-e, 6a-e), including bromine and iodine-containing benzo-analogues on a gram-scale scope and yields ranging from 82% to 99%. For the first time the synthesis of indole tris-heterocycles (7a, b) through the reaction of N-alkylation of the indole nitrogen atom is announced giving another potential synthetic application of the N,N-dialkoxycarbonyl-5,6-dimethylbenzimidazolium adducts.

Conclusion: The structure of the newly synthesized products is spectrally analysed and proved.

Background: α-Glucosidase inhibitors play an important role in the treatment of type 2 diabetes mellitus. Inhibitors of the latter enzyme that are available on the market created gastrointestinal side effects and achieve to a high potent and low side effect potent α- glucosidase inhibitors is a valuable target for medicinal chemists.

Objectives: In this study, derivatives of benzimidazole-phenoxy-1,2,3-triazole-benzyl skeleton were introduced as new α-glucosidase inhibitors.

Methods: Twelve derivatives 8a-l of target scaffold were synthesized via simple chemical reactions with a yield between 65 and 88%. The in vitro α-glucosidase inhibition activities of these compounds was evaluated against yeast form of this enzyme. After the determination of most potent compound, the interaction of this compound with α-glucosidase was evaluated in vitro by kinetic study and in silico by docking study. Drug-likeness, pharmacokinetics, and toxicity profiles of the most potent compound were predicted by an online software.

Results: Anti-α-glucosidase assay demonstrated that all synthesized derivatives 8a-l were more potent that standard inhibitor acarbose. Representatively, 2-(4-((1-benzyl-1H-1,2,3- triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazole (compound 8a) as the most potent derivative was 150-times more potent than positive control. Kinetic study of compound 8a revealed that this compound is an uncompetitive inhibitor against α-glucosidase. Furthermore, molecular docking study showed that compound 8a with favorable binding energy attached to important residues in the α-glucosidase active site. This compound also can be an oral drug with favorable toxicity profile.

Conclusion: Benzimidazole-phenoxy-1,2,3-triazole-benzyl derivatives 8a-l synthesized and evaluated for anti-α-glucosidase activity. All these compounds were excellent α-glucosidase inhibitor, and compound 8a demonstrated the most significant inhibition effect when compared with positive control.