A concise and efficient synthesis of the γ-lactam-fused azaphenanthrene alkaloid eupolauramine has been achieved. The key feature of the synthesis involves Au(I)-catalyzed cycloisomerization of N-naphthyl aminobutynamide intermediate and subsequent intramolecular Ullmann-type coupling reaction. This study clearly demonstrated the usefulness of coinage metal-catalyzed cycloisomerization strategy in the construction of architecturally sophisticated pyridine-fused heterocyclic scaffolds.
A one-pot, three-component reaction of ethyl 5-aminobenzofuran-2-carboxylate, arylglyoxals and cyclic 1,3-dicarbonyl compounds in the presence of acetic acid as an organocatalyst in ethanol medium under reflux conditions provided a series of new 6H-furo[3,2-e]indole derivatives in good yields.
This work presents the study results on the acid-catalyzed cascade condensation of p-toluenesulfonamide with glyoxal in H2SO4 in order to synthesize aza- and oxaazaisowurtzitanes—a platform for promising high-energy-density compounds—and explore their formation processes. The effects of the ratio of starting reactants, acidity, reaction medium concentration, and temperature on this process were studied in detail. Five novel compounds were derived, including four oxaazaisowurtzitanes comprising one to three aza groups, and one condensation intermediate. The most favorable conditions for the formation of the resultant caged compounds were established and some new regularities of the process were revealed. For instance, the reaction medium concentration was discovered for the first time to influence the generation process of oxaazaisowurtzitanes via direct condensation. The limiting stage of the cage formation process of oxaazaisowurtzitanes was identified. The formation rate of the oxaazaisowurtzitanes was shown to be dependent on their structure. The factor dramatically reducing the yield of the oxaazaisowurtzitanes at elevated synthesis temperature was also revealed.
First case of regiospecific formation of indole fused with a triterpene scaffold is observed. Starting from 3-oxo-24-nor-allobetulin Fischer reaction with phenylhydrazine under the influence of weak acid catalyst led to 3H-indole (indolenine) 4. This process was accompanied by a change in the configuration of the methyl group at C-4 that was confirmed by x-ray diffraction method. On the other hand, 3,2-indole 5 was synthesized under the influence of strong acid catalyst (using phenylhydrazine hydrochloride in AcOH acid or phenylhydrazine in MeOH with a few drops of HCl).
A series of novel [1,2,4]triazolo[4′,3′:1,5][1,2,4]triazolo[3,4-b][1,3,4]thiadiazines (4a-p) were synthesized from the reaction of 4-amino-5-hydrazinyl-4H-1,2,4-triazole-3-thiol (1) with different bromoethanones (2a-p) and substituted benzoic acids (3) via a one-pot, three-component reaction with good to excellent yields. The new fused tri-cyclic system was achieved without using a catalyst and metal by cyclo-condensation reaction through a one-pot approach. The structures of newly synthesized molecules were confirmed by using IR, 1H-NMR, 13C-NMR, Mass spectral, and analytical data. Molecular docking studies were carried out for the newly synthesized compounds against human cancer receptors (2TKB) with good results.
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.
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