Journal of Heterocyclic Chemistry最新文献

We reported here a straightforward strategy for the synthesis of pharmaceutically important 5,6-dihydropyrimido[4,5-d]pyrimidines through the reaction between N-uracil amidines and functionalized aldehydes under catalyst-free conditions. The condensation reactions between N-uracil amidines and aldehydes proceeded smoothly in water solvent in the presence of Cs₂CO₃ at 100°C for 15 h under nitrogen atmosphere. A range of aromatic aldehydes bearing electron-donating as well as electron-withdrawing groups were well tolerated under optimized reaction conditions and allowed the access of substituted 5,6-dihydropyrimido[4,5-d]pyrimidines in 64%–98% yields. The use of a green solvent, an easy work-up procedure, and a good to excellent yield of products makes this protocol attractive from a sustainable point of view.

The reaction of generated in situ 2,4-diaminothiazole with various aldehydes was investigated. For the first time, it was shown that the considered process leads to the formation of dithiazolo[4,5-b:5′,4′-e]pyridine system. Relied on the performed research, the general method for the preparation of substituted dithiazolo[4,5-b:5′,4′-e]pyridine-2,6-diamines was developed. The advantages of the elaborated synthetic procedure are easily available starting compounds, atom economy, and simple isolation of target products without chromatographic purification. The application of the presented approach to related 2,4-diaminoselenazole allowed us to design a previously unknown bis([1,3]selenazolo)[4,5-b:5′,4′-e]pyridine system. The structures of the two obtained dithiazolo[4,5-b:5′,4′-e]pyridine-2,6-diamines were confirmed by X-ray analysis.

A clean and highly regioselective three-step synthetic procedure to obtain two new series of novel 1,3-thiazolidine/1,2,3-triazole hybrids (3a–r and 5a–f) based on the copper-catalyzed alkyne-azide reaction (CuAAC) was developed. The key intermediaries, the 3-propioloyl-thiazolidine-4-carboxylic acid methyl esters (2a–e) and methyl 3-propargyl-thiazolidine-4-carboxylic acid methyl ester (4) were easily prepared from the corresponding thiazolidine-4-carboxylic acid methyl esters (1a–e), which were previously obtained from L-(+)-cysteine and some aromatic and aliphatic aldehydes with subsequent acylation reaction activated by carbodiimide with propiolic acid or the respective alkylation reaction using propargyl bromide. In addition, one new thiazolidine/isoxazole hybrid (6a) was also obtained through 1,3-dipolar cycloaddition reaction with the same click chemistry approach. All of the molecular hybrids reported here are promising models for future pharmacological studies, particularly for the development of cancer drugs, with a special focus on in vitro prostate cancer models.

A set of six hitherto unknown oxepinoxanthone derivatives has been prepared for cellular evaluation in view of the known and impressive anticancer potential of some pyranoxanthone derivatives. A set of three structurally similar pyranoxanthone derivatives has also been prepared for a direct comparison of biological activity associated with a change in ring size, from six to seven, if any. Evaluation of their anticancer properties was attempted in three different cancer cell lines, such as HPV, cervical cancer cell line HeLa, hormone-responsive breast cancer cell line MCF7, and lung cancer cell line A549, as many of the naturally occurring pyranoxanthones have shown effective activity against these cell lines. The oxepinoxanthone derivatives 15, 16, and 18 showed significant anticancer effects (selectivity index > 1–1.5), increasing reactive oxygen species generation, leading to apoptotic DNA laddering and nuclear blebbing. Though the pyran analogues 21 and 23 showed cytotoxicity in MCF7 and A549 cell lines, they also showed poor selectivity indices against breast cancer, cervical cancer, and lung cancer.

Morita-Baylis-Hillman carbonates are a versatile and emerging class of organic precursors, utilized in various organic transformations as a main reagent, yielding intricate functionalized moieties. These carbonates facilitate the synthesis of various bioactive entities, natural products, and other valuable compounds. MBH carbonates combined with other substrates such as phenolates, oxindole-chromones, enamino maleimides, isoquinolines, sulfones, cyclic ketimines/imines, and perfluoroalkyls, and so forth via substitution and annulation reactions provide valuable organic compounds. This review highlights the recent synthetic applications of these organic carbonates in the synthesis and functionalization of oxindoles, pyrazoles, quinolines, and organofluorides, and so forth.

The synthesis of functionalized pyrazole-4-carboximidamide with appropriate yields through a novel four-component reaction from alkynes, hydrazonoyl chlorides, trichloroacetonitrile, and various anilines is a remarkable achievement in heterocycle chemistry. This strategy offers a direct and efficient route to access different pyrazoles with amidine substitution from readily available starting materials. The use of copper (I) as a catalyst, in DMF solvent, without adding a ligand, and with the help of ultrasonic conditions for 50 min at room temperature highlights the importance of transition metal catalysis in this process. The combination of available starting materials, mild reaction conditions, catalytic systems, and ease of purification procedures contributes to the attractiveness of this method for the synthesis of diverse new substituted pyrazoles, including an amidine skeleton.

Quinoline derivatives represent a major family of N-containing heterocyclic compounds with various biological properties and a major role in medicinal and material chemistry. Traditional strategies for the preparation of quinolines typically rely on toxic reagents, dangerous by-products, and energy-demanding processes that represent substantial environmental and economic loss. Toward sustainable and efficient alternatives, green synthesis methods are developed that use environmentally friendly solvents, catalysts, and energy-saving techniques (microwave-assisted synthesis, solvent-free reactions, green solvents, biocatalysis, photocatalysis, nanocatalysis, ultrasonication, and catalyst-free synthesis). This review provides a broad overview of recent advancements in the green synthesis of quinoline derivatives, highlighting their potential to revolutionize conventional practices and contribute to sustainable development goals. The synthesis of quinoline derivatives has been covered in a number of reports, but most of them focus on either conventional or green methods independently. We present both approaches in a single, comparative framework in this review. The work aims to give researchers a clearer, more balanced understanding of the current methods and to support the exploration of more effective and environmentally friendly synthetic routes by describing their respective advantages, disadvantages, and practical challenges.

Trifluoromethyloxadiazole compounds (TFMO) are a class of anti-rust disease targeting histone deacetylases inhibitors (HDACs). In this paper, a series of 5-(trifluoromethyl)-1,2,4-oxadiazole substituted benzamide derivatives containing 5-(trifluoromethyl)-1,2,4-oxadiazole moiety were designed and synthesized. Anti-rust bioassay results showed some of them possessed excellent activities against Puccinia sorghi at 200 mg/L. Furthermore, the structure–activity relationship was established using in silico methods, and the most active compound binding mode was carried out based on the crystal structure of human HDAC1, human HDAC4, and human HDAC6. This work provided an excellent fungicide against rust for further optimization.

Imidazo[1,2-a]indoles, 2,3-dihydro-1H-imidazo[1,2-a]-indoles and benzo[4,5]imidazo[1,2-a]indoles are rare yet valuable classes of nitrogen-containing heterocycles, offering diverse applications in pharmaceutical development and advanced materials research. Despite their potential medicinal applications, efficient synthesis methods for these substances remain limited. This review provides an in-depth analysis of emerging synthetic approaches for imidazo[1,2-a]indoles and benzo[4,5]imidazo[1,2-a]indoles, including metal-catalyzed and metal-free methods, as well as metal-catalyzed synthesis of 2,3-dihydro-1H-imidazo[1,2-a]indoles, offering valuable insights into effective synthetic strategies.

In the research, we presented a method for synthesizing selenium-containing heterocyclic compounds. One of the key structures in this project is the derivative of 7-methyl-2-(alkylthio)-5-(amino-1-yl)-[1,3]selenazolo[5,4-d]pyrimidine (3a-i). These are synthesized in one step using the treatment of precursor 2,4-dichloro-6-methylpyrimidin-5-amine (1) with selenium and sodium borohydride in ethanol to obtain the compound, which subsequently reacts with carbon disulfide in pyridine to form 5-chloro-7-methyl-[1,3]selenazolo[5,4-d]pyrimidine-2(1H)-thione (2). This is then treated with various alkyl halides under reflux conditions in ethanol to yield various derivatives (3a-i). A mixture of 5-chloro-7-methyl-2-(alkylthio)-[1,3]selenazolo[5,4-d]pyrimidine (3a-i) and various primary and secondary amines is refluxed in ethanol to prepare the corresponding nucleophilic substituted products, 2-(alkylsulfanyl)-7-methyl-5-(morpholin-4-yl)-[1,3]selenazolo[5,4-d]pyrimidines (4a-i) in good yields.