Current organic synthesis最新文献

Background: This study investigated many cancer medicines using a wide range of degree sum-based topological indices and entropy. These numerical numbers, commonly referred to as topological indices or molecular descriptors, depict a substance's molecular structure. They have been successfully used to properly reflect different physicochemical properties in a number of Quantitative Structure-Property Relationship (QSPR) and Quanti-tative Structure-Activity Relationship (QSAR) research studies.

Objective: The purpose of the study was to investigate the relationships between topological neighborhood indices and physicochemical properties using the QSPR model and linear re-gression methodology.

Methods: We employed linear regression methodology within the QSPR model to examine the connections between physicochemical characteristics and topological neighborhood in-dices.

Results: The results revealed a significant correlation between the neighborhood indices un-der scrutiny and the physicochemical features of the potential drugs under investigation.

Conclusion: As a result, both neighborhood topological indices and entropy demonstrate potential as valuable tools for future QSPR investigations when evaluating anticancer medi-cations.

Introduction: The development of efficient and sustainable catalytic methodologies has garnered considerable attention in contemporary organic synthesis.

Methods: Herein, we present a novel approach employing the Cu@DPP-SPION catalyst for the synthesis of ethyl 4-(aryl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives. This versatile catalytic system incorporates copper nanoparticles supported on 4- (1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)benzoic acid-functionalized superparamagnetic iron oxide nanoparticles (SPIONs). The catalyst was meticulously characterized through scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), energy dispersive spectroscopy (EDS), and inductively coupled plasma (ICP) analysis. The catalytic process, exemplified by the synthesis of heterocyclic compounds, demonstrated high isolated yields, attesting to the robust performance of the catalyst.

Results: Furthermore, the reusability of the catalyst was validated through five consecutive reactions without a notable decrease in yield, while structural stability was confirmed by SEM analysis. The methodology combines green reaction conditions, room temperature operation, and facile magnetic catalyst separation, underscoring its potential for sustainable synthesis.

Conclusion: This work highlights the promise of the Cu@DPP-SPION catalyst as an innovative tool in heterogeneous catalysis and its role in advancing efficient and environmentally conscious synthetic methodologies.

Background: Timolol maleate is clinically used for the treatment of hypertension, angina pectoris, tachycardia, and glaucoma.

Objective: The aim of this study was to enhance the safe use of timolol maleate and investigate a synthesis method for 3-S-timolol, a newly identified impurity in timolol API (Active Pharmaceutical Ingredients).

Methods: (S)-3-(tert-butylamino)propane-1,2-diol (1) was used as a raw material. 3-S-timolol maleate (7) was synthesized through a five-step reaction. Overall yield was 57.7%, with a purity of 98%.

Results: The structure of the target compound was confirmed via analysis of its ¹H nuclear magnetic resonance, ¹³C nuclear magnetic resonance, and high-resolution mass spectrometry spectra.

Conclusion: The synthesis method was straightforward and yielded a high-purity product suitable for use as a reference in the analysis and identification of timolol maleate-related substances.

Background: Hexagonal fractals are intricate geometric patterns that exhibit selfsimilarity. They are characterized by their repetitive hexagonal shapes at different scales. Due to their unique properties and potential applications, hexagonal fractals have been studied in various fields, including mathematics, physics, and chemistry.

Objectives: The primary aim of this research is to provide a comprehensive analysis of hexagonal fractals, focusing on their topological indices, fractal dimensions, and their applications in structureproperty modeling. We aim to calculate topological indices to quantify the structural complexity and connectivity of hexagonal fractals. Additionally, we will determine fractal dimensions to characterize their self-similarity and scaling behaviour. Finally, we will explore the relationship between topological indices, fractal dimensions, and relevant properties through structure-property modeling.

Methods: A systematic approach was employed to investigate hexagonal fractals. Various topological indices were computed using established mathematical techniques. Fractal dimensions were determined. Structure-property modeling was conducted by establishing relationships between the calculated topological indices and fractal dimensions with experimentally measured properties.

Results: The research yielded significant findings regarding hexagonal fractals. A variety of topological indices were calculated, revealing the intricate connectivity and structural complexity of these fractals. Fractal dimensions were determined, confirming their self-similar nature and scaling behaviour. Structure-property modeling demonstrated strong correlations between the topological indices and fractal dimensions with properties such as conductivity, mechanical strength, and chemical reactivity.

Conclusion: This research provides valuable insights into the topological characteristics, fractal dimensions, and potential applications of hexagonal fractals. The findings contribute to a deeper understanding of these complex structures and their relevance in various scientific domains. The developed structure-property modeling approaches offer a valuable tool for predicting and controlling the properties of materials based on their fractal structure. Future research may explore additional applications and delve into the underlying mechanisms governing the relationship between fractal structure and properties.

Introduction: The reaction between 4-hydroxy-3,5-dimethoxyenzaldehyde and 2-nitroaniline has been discovered, and the final product has been identified such as 2-6-dimethoxy- 4-((2-nitrophenylimin)methyl)phenol (C1).

Materials and methods: X-ray diffraction examination per-formed on a single crystal provided conclusive evidence regarding the structure. Crystallography reveals that the two molecules A and B that were enclosed within the asymmetric unit are struc-turally distinct from one another. C-H·O, N-H·O, and O-H·O bonding is primarily respon-sible for the crystal packing stability. HO and off-set stacking interactions also contribute to the crystal packing's overall stability.

Results: To do further research into the intermolecular interactions, the Hirshfeld surface analysis technique is utilized. It is possible to determine the partiality of the interatomic contacts to create crystal packing interactions by computing the improvement ratio for those contacts. In addition, computational research is carried out with the B3LYP/6-31G(d,p) model to determine the amount of energy that is required for molecular pairs to interact.

Conclusion: The study concluded the roles those different kinds of interaction energy play in maintaining the stability of the molecular pair.

Nitrogen-containing heterocycles, such as indoles and quinolines, serve as the key scaffolds in numerous pharmaceuticals, pesticides, and natural products. The synthetic methods of nitrogen-containing heterocycles show significant scientific and industrial values. As a chemical intermediate featuring dual functional groups, cyanamide plays a crucial role in organic synthesis, directly affecting the development of new drugs and the design of new materials. Particularly in the synthesis of nitrogen-containing heterocyclic compounds, the cyano group can introduce various groups through radical pathways to synthesize polycyclic N-heterocyclic frameworks, as well as yielding a variety of nitrogen-containing heterocycles through non-radical pathways. This diverse reaction pathway makes the application of cyanamide in chemical synthesis more extensive and flexible. The progress involving cyanamide in the synthesis of quinazoline and quinazolinone, γ-lactams, and other nitrogen-containing heterocyclic frameworks is summarized. The main mechanisms and reaction strategies are emphasized and explicated from the perspective of radical and non-radical synthetic pathways, revealing the potential application value of these compounds in different fields. This review paves the way for the synthesis of various nitrogen-containing heterocyclic compounds, particularly in achieving green chemistry and sustainable development goals. These new methods and ideas are expected to promote the development of more efficient and economical synthesis strategies in the future, thereby advancing the widespread application of nitrogen-containing heterocyclic compounds in pharmaceuticals, agricultural chemicals, and new materials.

Background: Nitrogen mustards exert their anticancer activity by alkylating DNA. However, except for alkylating DNA, nitrogen mustards may alkylate other biomolecules to cause off-target effects due to their highly active functional groups. So, more exposure of DNA from chromosomes can facilitate the binding of nitrogen mustards to DNA to present stronger anticancer activity, simultaneously avoiding more side effects.

Objectives: To design and synthesize the 4-phenylbutanoic acid-chlorambucil conjugates and valproic acid-chlorambucil conjugates. Upon cellular internalization, the two conjugates can more strongly damage the DNA of cancer cells due to the more exposure of cellular DNA caused by 4-phenylbutanoic acid or valproic acid.

Methods: To validate this hypothesis, we designed and synthesized two hybrids of chlorambucil with 4-phenylbutanoic acid and valproic acid, denoted as compound 2a and compound 2b respectively. The antitumor activity of the aforementioned hybrids was evaluated by the MTT method, mitochondrial membrane potential analysis, apoptosis assay, DNA damage assay, and scratch assay respectively.

Results: Compound 2a and compound 2b were synthesized via esterification. The results of bioactivity evaluation showed compound 2a and compound 2b had stronger cytotoxicity against breast cancer MDA-MB-231 cells and MCF-7 cells than chlorambucil. More importantly, toward triple negative breast cancer MDA-MB-231 cells, compound 2a exhibited significantly greater cytotoxicity compared to both compound 2b and chlorambucil. Further studies were conducted on MDA-MB-231 cells, showing that compound 2a could more strongly decrease the mitochondrial membrane potential, induce cell apoptosis, and damage cellular DNA compared to compound 2b and chlorambucil. Interestingly, in combating the migration of MDA-MB-231 cells, the results exhibited that compound 2b had a much stronger anti-migratory effect than compound 2a, inconsistent with the aforementioned in vitro cytotoxicity.

Conclusion: These findings demonstrate that the combination of nitrogen mustards with histone deacetylase inhibitors is an effective strategy to exert synergistic anti-tumor effects.

Background: A direct synthesis of functionalized dimethyl fumarate derivatives of 2- (2-((E)-(2-oxoindolin-3-ylidene)methyl)-1H-benzo[d]imidazol-1-yl) is achieved via one-pot reaction involving 2-methyl-1H-benzo[d]imidazole and appropriate isatin in the presence of DMAD.

Methods: Conversely, this one-pot reaction furnished, upon conduction at 60 ° C, the 2-(2-((E)- (2-oxoindolin-3-ylidene)methyl)-1H-benzo[d]imidazol-1-yl) products. The biological activities were evaluated against JNK3 kinase. We chose to dock the compounds into the JNK3 binding site in order to comprehend the molecular underpinnings of the observed bioactivities.

Results: The structures of the synthesized compound adduct were evidenced from NMR and MS spectral data and further confirmed by single-crystal X-ray diffraction. The biological activities revealing that the introduction of an alkyl group at the 1-position of the isatin moiety produced JNK3 inhibitors with IC₅₀ values in the low micromolar range.

Conclusion: This study synthesized a unique compound using a three-component method. Compound 4d showed high antitumor activity (IC₅₀ = 6.5 μM) against JNK3 inhibitors, while compounds 4c, 4d, and 4f exhibited high selectivity. The research highlights the effectiveness of the one-pot reaction in creating medically useful hybrid compounds, marking a significant advance in medicinal chemistry.

Introduction: This study includes synthesis, characterizations, antimicrobial, antioxidant, and docking molecular study of novel Bis-Azetidinone compounds that combined two units of β-lactam rings .In the present investigation, the aromatic aldehydes with primary amine were condensed to create Schiff's base, which was then reacted with chloroacetylchloride to produce bis-Azetidinone compounds.

Methods: Melting points, FTIR, and NMR spectrum analyses were used to examine the morphological and topological characteristics of the Bis-Azetidinone compounds. The results indicate that the prepared Compounds synthesis has excellent antimicrobial activity against both Gram-negative (Escherichia coli,), Gram-positive bacteria (Staphylococcus aureus) and fungal (Candida albicans) and also indicated that the Compounds synthesis (A2) gave a higher antimicrobial effect than the B2, C2. The synergistic activity was examined against the pathogenic microbial strains. It was observed that employing compound synthesis combined with antibiotics enhanced the synergistic efficacy compared to using compound synthesis alone or antibiotic alone on Gram-positive bacteria and fungi.

Results: The antioxidant efficiency was assessed by DPPH, the results show that the compound synthesis has antioxidant activity, and also indicated that the synthesized compound (A2) gave a higher antioxidant effect than the B2, C2. Docking study confirmed via redocking of crystalized substrate or inhibitor within target binding pocket. The docking results reveal that the synthesized compounds, with a total binding affinity of less than -48 kcal/mol, could be clinically used for future therapeutic purposes.

Conclusion: The present research demonstrates the advantageous effectiveness of a simpler production procedure, novel Bis-Azetidinone compounds, for producing high-purity with low hazard that may be utilized as future possible medical therapies.