Current organic synthesis最新文献

Introduction: 1,4-oxazepine is a significant structural motif found in several bio-active molecules used in the treatment of diseases such as psychotic disorders.

Methods: Therefore, developing novel methodologies for its preparation is of great interest to medicinal chemists.

Results: These seven-membered heterocycles are generated through the intramolecular cy-clization of Betti bases, which are propargylated using propargyl bromide as the source of the triple bond in the presence of a base.

Conclusion: This efficient and straightforward protocol proceeds under mild, metal-free conditions and has been shown to be applicable to a broad range of aldehydes and 2-aminopyridines.

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.

Background: Nitrogen mustards exert their anticancer activity by alkylating DNA. However, except for alkylating DNA, nitrogen mustards may alkylate other bio-molecules 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.

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

Methods: To validate this hypothesis, we designed and synthesized two hybrids of chlo-rambucil 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 as-say, 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 cytotoxici-ty 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 ex-hibited significantly greater cytotoxicity compared to both compound 2b and chlorambu-cil. Further studies were conducted on MDA-MB-231 cells, showing that compound 2a could more strongly decrease the mitochondrial membrane potential, induce cell apopto-sis, 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 ef-fects.

Background: o-Aminophenol derivatives are of particular interest for their di-verse biological activities and potential therapeutic applications. Such as, antioxidant, an-tibacterial, and cytotoxic activities.

Objective: This study aimed to design and synthesize a series of novel o-aminophenol de-rivatives through an efficient multi-step process, characterize them using modern spectro-scopic techniques, and evaluate their antimicrobial, antioxidant, and cytotoxic activities.

Methods: A series of novel derivatives of o-aminophenol have been successfully synthe-sized with very high efficiency through a simple six-step process using readily available chemicals and straightforward reactions. The structures of all products were accurately de-termined using modern spectroscopic methods such as 1D and 2D NMR, as well as IR, MS spectroscopy, and X-ray methods. The antimicrobial activities of eight o-nitrophenol derivatives were assessed against Gram (-) and Gram (+) bacteria as well as fungi. In comparison, antioxidant activities were tested for two o-nitrophenol and 11 o-aminophenol derivatives using SC50 and EC50 assays. Cytotoxicity was evaluated on KB, HepG2, A549, and MCF7 cancer cell lines.

Results: Six synthesized compounds 5b, 5c, 5g, 6b, 6c, 6g exhibited unusual doublet sig-nals in the H8 region of the 1H NMR spectrum, attributed to atropisomer formation. Eight o-nitrophenol derivatives demonstrated weak antimicrobial activity, with MIC values ranging from 100 to 200 μg/mL. Compound 5g showed activity against all tested bacterial and fungal strains. In antioxidant testing, eight o-aminophenol derivatives 6a, 6b, 6c, 6e, 6f, 6h, 6i, and 12b displayed excellent activity, with SC50 values between 18.95 and 34.26 μg/mL, approaching ascorbic acid's SC50 value of 12.60 μg/mL. Three derivatives 6d, 6g, and 12a showed superior antioxidant activity with EC50 values between 4.00 and 11.25 μg/mL, surpassing quercetin's standard of 9.8 μg/mL. Cytotoxicity assays revealed that o-aminophenol derivatives 6b, 6c, 6f, 6i, and 12b exhibited moderate inhibitory effects on KB cell lines with IC50 values from 32 to 74.94 μg/mL. Compound 6i demonstrated mod-erate cytotoxic activity against HepG2, A549, and MCF7 cell lines, with IC50 values of 29.46, 71.29, and 80.02 μg/mL, respectively.

Conclusion: Design, synthesis, antimicrobial activity, DPPH Radical Scavenging, Cyto-toxic activity, Evaluation of H8 signal anomalies in certain compounds, and Single crystal X-ray diffraction analysis.

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 tris-heterocyclic hybrids. The structure of newly obtained products was spectrally charac-terized by 1D and 2D-NMR, FTIR and HRMS spectral data. The current scientific re-search 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 benzazaca-malexin 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 ben-zimidazoles 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 an-other 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: Hexagonal fractals are intricate geometric patterns that exhibit self-similarity. They are characterized by their repetitive hexagonal shapes at different scales. Due to their unique properties and potential applications, hexagonal fractals have been stud-ied in various fields, including mathematics, physics, and chemistry.

Objective: The primary aim of this research is to provide a comprehensive analysis of hex-agonal fractals, focusing on their topological indices, fractal dimensions, and their applica-tions in structure-property 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 prop-erties through structure-property modeling.

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

Results: The research yielded significant findings regarding hexagonal fractals. A variety of topological indices were calculated, revealing the intricate connectivity and structural com-plexity 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 scien-tific domains. The developed structure-property modeling approaches offer a valuable tool for predicting and controlling the properties of materials based on their fractal structure. Fu-ture research may explore additional applications and delve into the underlying mechanisms governing the relationship between fractal structure and properties.

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 and objective: Despite the well-known antibacterial activity of cephalosporins, their analogous spirocyclic derivatives have not been adequately evaluated. Thus, this work aimed to prepare a series of novel 3-spirocephalosporins and evaluate their antibacterial activity.

Materials and methods: Novel 3-spirocephalosporins were prepared through a one-pot thioalkylation of chloromethyl cephalosporin GCLE with a range of 1,2,4-triazolidine-3- thiones, followed by intramolecular Michael addition to the generated dihydrothiazine ring. The reaction was performed at room temperature under basic conditions (K2CO3, acetone, H2O). The antibacterial activities of the synthesized compounds were evaluated against a panel of Gram-positive and Gram-negative bacteria.

Results: Most targets were obtained in moderate yield, and their structures were confirmed by 1H and 13C NMR spectral techniques. All the tested compounds exhibited antibacterial activity against methicillin-resistant S. aureus.

Conclusion: Seven novel thiazolidine-bearing 3-spirocephalosporins were prepared, and most of them were potent against Gram-positive bacteria. Likely, the replacement of 1,2,4- triazolidine-3-thiones with other heterocycles containing bidentate nucleop.

Nitrogen-containing heterocycles, such as indoles and quinolines, serve as the key scaffolds in numerous pharmaceuticals, pesticides, and natural products. The synthesis methods of nitrogen-containing heterocycles show significant scientific and industrial value. 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 vari-ous 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 di-verse reaction pathway makes the application of cyanamide in chemical synthesis more extensive and flexible. The progress involving cyanamide in the synthesis of quinazoline and quinazoli-none, 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 het-erocyclic 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.