Search Results (90)

Kynurenic acid (KYNA) derivatives condensed with an aromatic ring (tricyclic KYNA derivatives) have been successfully synthesized, and the reactivity of these analogues has been investigated in the modified Mannich reaction resulting in new Mannich bases. The N,N-dimethyl-ethylenediamine analogues of the tricyclic KYNA derivatives have also been successfully synthesized, and their reactivity in the modified Mannich reaction was investigated. The synthesized ring systems bear resemblance to molecules previously investigated as G-quadruplex binding agents. Based on this similarity, the synthesized tricyclic KYNA derivatives could be investigated as potential antiviral and anticancer molecules. Full article

A stereoselective and scalable strategy for the synthesis of phosphorus-containing bicyclic and tricyclic compounds from 1-phenylphosphin-2-en-4-one 1-oxide is presented. This activated dienophile, available in both racemic and enantiopure forms, undergoes smooth [4+2] cycloadditions with acyclic and cyclic dienes, affording products with excellent yields and controlled stereochemistry. Notably, the cis/trans-fusion of the cycloadducts (phosphadecalones and phosphahexahydrochrysene) can be selectively controlled by fine-tuning the conditions of microwave-assisted cycloaddition reaction. The influence of temperature, time, and steric effects on cis/trans and endo/exo selectivity was examined in detail. The molecular structure, including the absolute configuration, of eight products has been determined by X-ray crystallography. These analyses further established the endo-selective nature of the cycloaddition, favoring the P=O face of the dienophile. Post-cycloaddition transformations of selected P-stereogenic phosphadecalone, such as isomerization, reduction and deoxygenation, demonstrate the synthetic versatility of the resulting products. Full article

The diastereoselectivity of the liquid- and vapor-phase Catalytic Transfer Hydrogenation (CTH) of cyclic ketones: x-methylcyclohexanones (x = 2, 3 or 4), 4-t-butylcyclohexanone, and bicyclic ketones: 2-norbornanone, camphor, fenchone, and a tricyclic ketone (2-adamantanone) with secondary alkanols (2-propanol, 2-butanol, 2-pentanol, or 2-octanol) as hydrogen donors in the presence of ten metal oxides as the catalysts was studied. Among the oxides, only four, namely, MgO, ZrO₂·nH₂O, ZrO₂, and Al₂O₃, exhibited good or high activity. The reaction products are diastereoisomeric alcohols, the relative ratio of which depends on the structure of the ketone, mode of reaction, temperature, and, in the liquid-phase mode, reaction time. The results of vapor-phase CTH revealed that, in this mode of reaction, the diastereoselectivity to the trans isomer is lower than in the liquid phase. For the three x-methylcyclohexanones, the most pronounced difference between the experimental values and reference values was noted for x = 3. For bicyclic ketones, the implementation of heterogeneous catalysts allowed us to obtain a substantial excess of the less favorable diastereomer. In the case of 2-norbornanone, the thermodynamic equilibrium mixture contains 21% endo and 79% exo alcohols, whereas our product mixtures contained up to 79% of the endo isomer. Full article

Designing bifunctional catalysts for efficient hydroisomerization of phenanthrene to alkyl-adamantane is a great challenge for producing high-density fuels. Herein, a bifunctional Pt catalyst was fabricated by developing hierarchical H-MSY-T zeolites with an NOA-co strategy. The influence of different mesopore template agents on the hierarchical structure of H-MSY-T zeolite was investigated. Effective regulation of pore structure and acid distribution of zeolites was achieved by adjusting the templating agents. The block copolymer P123 promoted the formation of mesoporous structures via self-assembly with a large mesopore centered at 8 nm. Large mesoporous structure and suitable distribution of Bronsted acid boosted the hydroisomerization of phenanthrene. The highest alkyl-adamantane yield of 45.9 wt% was achieved on the Pt/MSY-P1 catalyst and a reaction network of hydroisomerization was proposed. This work provides guidance to design highly selective bifunctional catalysts for the one-step hydroconversion of tricyclic aromatic hydrocarbons into high-density fuels. Full article

Spirocalcaridines A and B are among the most challenging members of the marine invertebrate-derived Leucetta alkaloids. Approaches to the construction and elaboration of the highly compact spirocyclic core are described. The synthesis of tricyclic guanidine via tandem oxidative amination dearomatizing spirocyclization (TOADS) using hypervalent iodine set the stage for total synthesis via the migration of the C4/C8 double bond to the C4/C5 position, followed by oxidation. The undesired but not surprising propensity of the spirocyclic cyclohexadienone to undergo rearrangement to the phenol hindered the desired olefin migration. Furthermore, initial efforts to install the oxidation sequentially, first at C5 and then at C4 in the complete carbon skeleton, were fraught with unforeseen challenges and unusual outcomes. In addition, the scope and limitations of hypervalent iodine-mediated tandem oxidative dearomatizing spirocyclization on various substrates were explored. Urethanes and thiourethanes underwent spirocyclization with an excellent yield, whereas the reaction with allylic substrates and species lacking the p-methoxy substituent did not proceed. Attempts to prepare other guanidine precursors are briefly discussed. Full article

Background/Objectives: Fungal pathogens are increasingly developing concerning resistance against the currently available antifungal drugs, which creates a constant demand for new antifungal agents. Methods: Here, we report the synthesis of C3,N4-substituted triazole derivatives containing a N4-(2-((4-methoxybenzyl)thio)phenyl) group. By selectively removing the 4-methoxybenzyl group, we were able to access the free thiol analogs which, under oxidative conditions, undergo a cyclization reaction yielding a C5-substituted benzo[4,5]thiazolo[2,3-c][1,2,4]triazole. We were able to show a broad functional group tolerance for the preparation of the triazole derivatives, as well as the tricyclic heteroarenes prepared thereof. Mechanistic investigations suggest that the oxidative cyclization reaction proceeds via an ionic pathway involving a disulfide intermediate. Isolation of the disulfide intermediate and resubjecting it to the reaction conditions shows that the presence of acid significantly increases its rate of conversion to the corresponding benzo[4,5]thiazolo[2,3-c][1,2,4]triazole. Antifungal testing of both the novel triazoles and the benzo[4,5]thiazolo[2,3-c][1,2,4]triazoles was carried out with Candida albicans (SC5314) and a clinical strain of Trichosporon asahii (OK01). Results: Most of the novel sulfur-containing triazoles and benzo[4,5]thiazolo[2,3-c][1,2,4]triazoles showed activity against Candida albicans (SC5314) and the emerging pathogen Trichosporon asahii (OK01). Conclusions: A series of new sulfur-containing triazoles and benzo[4,5]thiazolo[2,3-c][1,2,4]triazoles were synthesized. Antifungal testing revealed modest activity against Candida albicans (SC5314) and Trichosporon asahii (OK01). Full article

Atherosclerosis, a chronic inflammatory disease, is driven by complex molecular mechanisms involving inflammatory cytokines and immune pathways. According to recent research, tricyclic antidepressants (TCAs), which are typically prescribed to treat depressive disorders, have strong anti-inflammatory effects. TCAs, including imipramine and amitriptyline, alter inflammatory signaling cascades, which include lowering the levels pro-inflammatory cytokines like TNF-α, IL-1β, and IL-6 and inhibiting NF-κB activation. By inhibiting the NLRP3 inflammasome and suppressing pathways including JAK/STAT, MAPK, and PI3K, these effects are produced, improving endothelial function and reducing oxidative stress. The intricacy of TCAs’ anti-inflammatory actions has demonstrated by the existence of contradictory findings about how they alter IL-6 levels. The dependence of the heterogeneity of the reaction on the use of particular TCAs and experimental settings is shown by the fact that some studies show reduced IL-6 production, while others indicate increases or no changes. This review explores the multifaceted mechanisms through which TCAs modulate inflammatory pathways. TCAs inhibit NF-κB activation, reduce oxidative stress, and suppress the production of key inflammatory mediators, including IL-6 and TNF-α. They also regulate Toll-like receptor (TLR) signaling and NOD-, LRR-, and NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome activation, reducing the release of IL-1β and IL-18, critical drivers of endothelial dysfunction and plaque instability. Given their capacity to target critical inflammatory molecules and pathways, TCAs provide great potential in the therapy of atherosclerosis, particularly for individuals with associated depression and cardiovascular risk factors. Nevertheless, further research is essential to clarify the precise molecular mechanisms, resolve inconsistencies in current findings, and establish the clinical applicability of TCAs as anti-inflammatory agents in atherosclerosis management. Full article

A first syn-type tricyclic 8-8-8 (three fused-8-membered ring) laddersiloxane functionalized with four azido groups was successfully synthesized through efficient and highly selective hydrosilylation and nucleophilic substitution, achieving an excellent overall yield. The starting material, a tetravinyl-substituted 8-8-8 laddersiloxane, was prepared via a straightforward and scalable method. The obtained azido-functionalized ladder compound, fully characterized, constitutes a versatile building block for hybrid materials. Reacting this compound with 2-ethynylpyridine via click chemistry yielded a multidentate ligand containing four 2-triazole-pyridyl moieties. This N,N-bidentate ligand was subsequently employed in copper-catalyzed alcohol oxidative dehydrogenation reactions, demonstrating its potential in catalysis. Full article

Oxazole, a versatile and significant heteroarene, serves as a bridge between synthetic organic chemistry and applications in the medicinal, pharmaceutical, and industrial fields. Polycyclic aromatic compounds with amino groups substituted at the 2-position of an oxazole, such as 2-aminonaphthoxazoles, are expected to be functional probes, but their synthetic methods are extremely limited. Herein, we describe electrochemical reactions of 3-amino-2-naphthol or 3-amino-2-anthracenol and isothiocyanates in DMSO, using a graphite electrode as an anode and a platinum electrode as a cathode in the presence of potassium iodide (KI), which afford N-arylnaphtho- and N-arylanthra[2,3-d]oxazol-2-amines via cyclodesulfurization. This reaction is the first example of synthesis of 2-aminoxazole-based polycyclic compounds using an electrochemical reaction. An examination of the spectroscopic properties of polycyclic oxazoles revealed that the λ_abs value of the tetracyclic oxazoles was redshifted relative to that of the tricyclic oxazoles. Moreover, synthesized naphthalene/anthracene-fused tricyclic and tetracyclic oxazoles exhibited extended π-conjugated skeletons and fluoresced in the 340–430 nm region in chloroform. Full article

Isoquinoline derivatives exhibit a range of biological properties, including antibacterial activity, and are thus attractive as a scaffold for developing broad-spectrum antibacterial compounds. A series of six isoquinoline-based compounds were synthesized using the reaction of 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline with dimethyl acetylenedicarboxylate (DMAD) to provide the tricyclic (2Z)-[2-oxo-5,6-dihydropyrrolo[2,1,a]isoquinolin-3-ylidene]-2-ethanoate. The [2 + 3] cycloaddition of DMAD with C-6 and C-7 substituted 1-methyl-3,4-dihydroisoquinolines proceeded using aryl ethers or unsubstituted compounds, but not with amine, amide or nitro moieties at the C-7 position. Compounds 8d and 8f were found to have antibacterial properties against some Gram-positive pathogens (Staphylococcus aureus—8d = 16 µg/mL, 8f = 32 µg/mL; Streptococcus pneumoniae—8f = 32 µg/mL; and Enterococcus faecium—8d = 128 µg/mL, 8f = 64 µg/mL). Evaluation of their cytotoxic properties against mammalian cell lines revealed some cytotoxic effects (8b and 8d, 125 µM, 24 h, HEp-2 cells) and (8a, 8b, 8d = 125 µM, 8f = 62.5 µM, 24 h, McCoy B cells), suggesting limitations in their antibacterial applications without further development. Full article

Background: The increasing prevalence of antimicrobial resistant highlights the urgent need for the new therapeutic agents. This study aimed to design and synthesize fused tricyclic benzimidazole–thiazinone derivatives (CS1–CS10) through a convenient method and evaluate their antimicrobial activity against various microorganisms. Methods: A series of fused tricyclic benzimidazole–thiazinone derivatives was rationally designed and synthesized in one pot by the reaction between trans substituted acrylic acids and 1H-benzo[d]imidazole-2-thiol using coupling reagent TBTU (2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate). The structure of these compounds was confirmed through various spectroscopic techniques like IR, ¹H and ¹³C NMR, the DEPT and 2D-HMQC NMR techniques were also performed to confirm the relation of both carbon and proton. Further, the compounds were in vitro evaluated for their effectiveness against the Candida species and a panel of standard bacterial isolates. Results: The synthesized compounds showed moderate antimicrobial activity. Among all of the compounds, CS4 exhibited potent inhibition against Pseudomonas aeruginosa and Escherichia coli at 256 and 512 μg/mL concentrations, respectively. Additional research indicated that compound CS4 demonstrated a synergistic effect after combining with the standard antibacterial drug ciprofloxacin. Conclusions: These results suggest that CS4 is the best-synthesized antibacterial agent particularly in combination therapies. These findings highlight its promise for further development as a novel antibacterial agent. Full article

We report herein that bis(tricyclic) aromatic enes (BAEs) consisting of 6-6-6-membered frameworks such as acridine, xanthene, thioxanthene, and thioxanthene-S,S-dioxide act as a new class of organic luminophores that exhibit blue-to-green fluorescence in the solid state and in polymer film with good to excellent quantum yields. The BAEs were prepared by the palladium-catalyzed double cross-coupling reaction of phenazastannines or 10,10-dimethyl-10H-phenothiastannin with 9-(dibromomethylene)xanthene, 9-(dibromomethylene)thioxanthene, or 9-(dibromomethylene)-9H-thioxanthene-10,10-dioxide. Microcrystals or powder samples of the BAEs exhibited brilliant fluorescence with good to high quantum yields (Φ = 0.45–0.88). Furthermore, more efficient emission of blue-to-green light (Φ = 0.59–0.91) was observed for the BAEs dispersed in the poly(methyl methacrylate) (PMMA) films. Density functional theory (DFT) calculations suggest that the photo-absorption of the (thio)xanthene moiety-containing BAEs proceeds via π–π* transitions, whereas the optical excitation of 10,10-dioxido-9H-thioxanthene moiety-containing BAEs involves an intramolecular charge transfer from the acridine/thioxanthene part to the electron-accepting 10,10-dioxido-9H-thioxanthene moiety. Full article

As the most common psychiatric symptom, depression represents a subject of high interest for the medical community. Background/Objectives: International guidelines consider selective serotonin reuptake inhibitors (SSRIs) the first-line treatment of depression. Although having better efficacy and tolerability in comparison to tricyclic antidepressants or monoamine oxidase inhibitors, the diversity and potential severity of adverse effects and interactions manifested by SSRIs, combined with the frequency of prescriptions, lead to the necessity of evaluating real-world data. The aim of this study was to identify and evaluate the drug interactions reported in EudraVigilance (EV) for the six SSRIs representatives that are authorized in Europe: fluoxetine (FXT), fluvoxamine (FVM), citalopram (CIT), escitalopram (ESC), paroxetine (PAR) and sertraline (SER). The entire class of SSRIs was examined as a comparator to identify whether one of the representatives was more prone to reporting. Methods: Descriptive analysis and disproportionality analysis were conducted on data extracted from the EV database. Results: A total of 326,450 adverse reactions (ADRs) were reported for the SSRIs group. Approximately a quarter of these (n = 83,201; 25.46%) were reported for SER and 22.37% (n = 73,131) for PAR. Of the total ADRs reported, 2.12% (n = 6925) represent preferred terms related to drug-drug interactions (DDIs): SER (n = 1474; 22.37%), CIT (n = 1272, 19.86), and FXT (n = 1309, 19.83%). Specific ADRs related to inhibitory activity represent 0.98%, and for potentiating activity, 1.89%. Conclusions: Although representing a small value of the total ADRs, DDIs may be related to severe outcomes. Awareness should be raised for this category of ADRs that can be reduced by the joined efforts of physicians and pharmacists. Full article

The chemical reaction of 2-(methylsulfinyl)naphtho[2,3-d]thiazole-4,9-dione (3) using different amines, including benzylamine (4a), morpholine (4b), thiomorpholine (4c), piperidine (4d), and 4-methylpiperazine (4e), produced corresponding new tricyclic naphtho[2,3-d]thiazole–4,9–dione compounds (5a–e) in moderate-to-good yields. The photophysical properties and antimicrobial activities of these compounds (5a–e) were then characterized. Owing to the extended π-conjugated system of naphtho[2,3-d]thiazole–4,9–dione skeleton and substituent effect, 5a–e showed fluorescence both in solution and in the solid state. The introduction of nitrogen-containing heterocycles at position 2 of the thiazole ring on naphtho[2,3-d]thiazole-4,9-dione led to large bathochromic shifts in solution, and 5b–e exhibited orange-red fluorescence with emission maxima of over 600 nm in highly polar solvents. Staphylococcus aureus (S. aureus) is a highly pathogenic bacterium, and infection with its antimicrobial-resistant pathogen methicillin-resistant S. aureus (MRSA) results in serious clinical problems. In this study, we also investigated the antimicrobial activities of 5a–e against S. aureus, MRSA, and S. epidermidis. Compounds 5c with thiomorpholine group and 5e with 4-methylpiperazine group showed potent antimicrobial activity against these bacteria. These results will lead to the development of new fluorescent dyes with antimicrobial activity in the future. Full article

Natural products play an important part in synthetic chemistry since they have many pharmacological properties and are used as active drug compounds in pharmaceutical chemistry. However, synthesis of these complex molecules is difficult due to the requirement of various synthetic steps, which include highly regio- and stereoselectivity. Therefore, oxidative radical cyclization assisted by manganese(III) acetate serves as an important step in obtaining spiro-, tricyclic, tetracyclic, and polycyclic derivatives of these compounds. Manganese(III)-based reactions offer a single-step regio- and stereoselective cyclizations and α-acetoxidations, reducing the number of synthetic steps. Also, the manganese(III)-mediated oxidative free radical cyclization method has been successfully applied for the synthesis of cyclic structures found in many natural products. This article presents a broad overview of manganese(III)-based radical reactions of natural products as a key step in overall synthesis. The authors have classified natural product synthesis processes assisted by manganese(III) acetate as intermolecular, intramolecular, oxidation, acetoxidation, aromatization, and polymerization reactions, respectively. Full article