Journal of Heterocyclic Chemistry最新文献

A diastereoselective synthesis for the preparation of (R)-methyl pipecolate and dextro-erythrophacetoperane, analogs of methylphenidate, drugs used to treat attention deficit hyperactivity disorder, is reported. The key steps involve a high diastereoselective ring-closing reaction via enolate formation and a diastereoselective ketone reduction reaction. The total synthesis of these valuable drugs could be obtained in only 5 and 8 steps, respectively, starting from (S)-(−)-methyl benzylamine.

A novel and convenient method for the synthesis of 1,2,4-oxadiazole-5-thiones with carbon disulfide as effective C=S source has been developed in a super basic condition. The presented method has a broad substrate scope, and various corresponding 1,2,4-oxadiazole-5-thiones have been obtained in good to excellent yields. This method allows to the gram-scale synthesis of products. Under similar conditions, synthesis of diazole thione benzothioamide derivative from p-cyanobenzamidoxime with CS₂ has been successfully achieved.

The compact, nitrogen-rich structure of 2,4,6,8,10,12-hexaazaisowurtzitanes calls attention among researchers worldwide. These compounds have found the greatest utility as substrates for nitration to obtain the caged polynitramine, 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane, which possesses a high-energy performance. All new derivatives of hexaazaisowurtzitane are nitratable. The present study examined the nitration process of 2,6,8,12-tetraacetyl-2,4,6,8,10,12-hexaazaisowurtzitane derivatives obtained through the condensation reaction with aldehydes under various conditions to yield CL-20. The yield of CL-20, a well-known nitration product of hexaazaisowurtzitane compounds, was found to depend on the substrate structure and the nitrating mixture composition. The revealed dependence of the synthesis of various nitrated compounds on the holding time enables the synthesis of products with different physicochemical properties in a single process.

For the first time, the possibility of using hexafluoro-1,4-naphthoquinone for the construction of condensed heterocyclic system was demonstrated. As a result, two-step synthesis of previously unknown 5,6,7,8-tetrafluoro-1H-benzo[f]indol-4,9-dione derivatives was elaborated. The suggested method includes initial interaction of hexafluoro-1,4-naphthoquinone with various methyl 3-aminocrotonates and subsequent intramolecular cyclization into the target fluorinated benzo[f]indole-4,9-diones. The distinctive feature of considered protocol is regiospecific reaction of fluorine atoms in quinone fragment. Advantages of the presented approach are simple synthetic procedure avoiding chromatographic purification, atom economy and readily available starting materials. The structure of one of the synthesized compounds was established by x-ray analysis.

The novel serious of tricyclicthiazolo[5,4-d]pyrimidinone were designed and synthesized as acetylcholinesterase (AChE) inhibitor agents. The main factors affecting the reactions of syntheses and the structure–activity relationships (SARs) were investigated as well. All compounds were confirmed by ¹H NMR, ¹³C NMR, and HRMS. The in vitro enzyme assays proved that most of the compounds effectively inhibited AChE in the micromolar range with little cytotoxicity. Especially the compound G15 exhibited the best inhibitory activity against AChE with IC₅₀ values of 4.41 ± 0.46 μM. Furthermore, kinetic analysis and molecular modeling studies pointed out the competitive inhibition manner of G15 on AChE. Thus, the derivative G15 can be considered a promising leading compound on AChE.

A series of phenyl, substituted phenyl and thiophene bearing dihydrofuropyrimidin-4-ones (3a-p) were synthesized by Mn(OAc)₃ mediated, microwave irradiated radical cyclizations of 2-hydroxy-pyridopyrimidin-4-one derivatives (1a-j) with substituted phenylvinylthiophenes (2a-c) at 70°C in 2 min. Compounds 3a-j was obtained between 28% and 66% yields. Molecular structures of 3a-p were determined by ¹H NMR, ¹³C NMR, ¹⁹F NMR, FTIR and HRMS techniques. Inhibitory activity of 3a-p were evaluated against Acetylcholinesterase (AChE) and inhibition results of these compounds showed that the compounds had good inhibition with IC₅₀ values between 0.52 and 3.77 μM. In addition, molecular docking studies were carried out on the most potent inhibitory compounds 3d (IC₅₀ = 0.64 μM), 3p (IC₅₀ = 0.52 μM) and standart drug Donepezil. The binding energies for 3d, 3p and Donepezil are −9.12, −10.08 and −12.65 Kcal/mol, respectively. Based on these results, it was determined that, compounds 3d and 3p are promising AChE inhibitors.

Condensation of α-arylaminoketones bearing 3-hydroxypyran-4-one fragment with thiourea was studied. Based on considered investigation, the method for the synthesis of terarylenes with 2-aminothiazole bridge was elaborated. The presented process is the first example of construction of thiazole core starting from α-aminoketone precursor. The advantages of developed approach are easily available starting materials and convenient isolation of target products avoiding chromatographic purification. The structure of one of prepared products was confirmed by x-ray analysis. The synthetic utility of obtained 2-aminothiazoles with allomaltol substituent was demonstrated by reaction at amino and hydroxyl groups.

Pyrimidine and its derivatives play a paramount role in drug discovery as privileged pharmacophores with considerable chemical and biological significance and its presence in genes. This review aims to assemble a systematic evaluation of synthetic tactics of various fused pyrimidine derivatives containing nitrogen heterocycles such as pyridopyridines, pyridopyrimidines, and pyrimidopyrimidine from a pharmacological point of view and deliver an overview of methodologies presenting the chemistry of fused pyrimidine derivatives. The review details the importance of various catalysts and ring substitution using various electrophilic and nucleophilic reagents. These synthetic strategies were elaborated based on the different synthetic routes that lead to the specific type of pyrimidine and pyridine fused derivatives. The literature accumulates various developments in one-pot condensation, the Knoevenagel–Michael addition mechanism, microwave and ultrasound irradiation, intramolecular cyclization, nano-catalytic reactions, and so forth. Short reaction times, catalyst reusability, solvent-free conditions, excellent yields, and stereo-selectivity are some of the benefits of certain synthetic approaches.

A regioselective synthesis of 4H-pyrano[2,3-b]quinoline derivatives via DABCO-mediated Knoevenagel condensation/heterocyclization sequence has been executed. In this way some new fused heterocyclic compounds were synthesized from 2-chloroquinoline-3-carbaldehyde as a versatile and efficient synthetic building block. The one-pot three-component reaction of 2-chloroquinoline-3-carbaldehyde and diverse cyclic active methylenes for construction of highly substituted quinolines scaffold has been accomplished under mild condition. The strategy included herein shows significant advantages, including a facile process with easy purification, excellent yields, wide applicability, available substrates, and cost-effective/eco-friendly solvent and catalyst.

In this work, we report the synthesis of a series of new 4H-1,3,5-oxadiazine derivatives. The method of their production is based on the dehydrosulfurization reaction of N-(2,2,2-trichloro-1-(3-R-thioureido)ethyl)carboxamides under the action of a mixture of iodine and triethylamine in DMF. A possible reaction mechanism has been proposed. The target products have been obtained in 58%–75% yield. The structure of the obtained compounds has been confirmed by ¹H, ¹³C NMR, IR spectroscopy data, and x-ray diffraction analysis carried out for 6-(tert-butyl)-N-phenyl-4-(trichloromethyl)-4H-1,3,5-oxadiazin-2-amine.