Search Results (41)

Nitrogen-containing heterocycles of 3-pyrrolin-2-one series are widely represented in natural and synthetic compounds, with a broad spectrum of pharmacological activity and considerable potential in medicinal and synthetic organic chemistry. In this communication, we report the previously unknown acid-catalyzed transformation of a N-substituted derivative of 3-pyrrolin-2-one that generates two types of heterocyclic moieties. The reflux of 1-benzyl-3-chloro-5-hydroxy-4-[(4-methylphenyl)sulfanyl]-1,5-dihydro-2H-pyrrol-2-one in toluene in the presence of catalytic amounts of H₂SO₄ resulted in the formation of a mixture of 1-benzyl-3-[(4-methylphenyl)sulfanyl]-1H-pyrrole-2,5-dione and 1-benzyl-7-methyl-1H-benzo[4,5]thieno[3,2-b]pyrrole-2,3-dione. The structures of four novel nitrogen-containing heterocycles were elucidated through IR, NMR spectroscopy and HRMS spectrometry. A new derivative of the fused tricyclic compounds, possessing benzo[b]thiophene and pyrrole-1,2-dione fragments, was also characterized by single-crystal X-ray diffraction. Full article

Pyridazin-3(2H)one-based molecules have always attracted the attention of medicinal chemists due to their different pharmacological properties. The incorporation of such nuclei in therapeutically active molecules either as monocyclic units or as fused bi- or tricyclic scaffolds results in a wide range of pharmacological effects such as anti-inflammatory, analgesic, anticancer, antimicrobial, antiviral, cardiovascular-protective, antiulcer, and many other useful pharmacological activities. In accordance with our consolidated experience gained over the years in the chemistry and biology of tricyclic pyridazin-3(2H)ones, this review summarizes SAR studies of such pyridazinone-based polycyclic compounds endowed with various biological and therapeutic properties. Full article

A novel class of chiral sulfonium salts, derived from L- and D-methionine, was designed and successfully employed for the diastereoselective synthesis of epoxy amides. This new methodology of asymmetric epoxidation was exploited for the stereoselective construction of fused polycyclic ethers, which are structural motifs present in a great variety of natural products of marine origin. This methodology proved to be useful for the synthesis of the tricyclic A–C system contained in yessotoxin and adriatoxin, and also in many other related natural products of marine origin belonging to the fused polycyclic ether toxins. 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

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

The reaction of (Z)-5-phenyl-1,3-di-p-tolylpent-2-en-4-yn-1-ol (1) with trimethylsilyl chloride in dichloromethane at ambient temperature gave a dimeric ether compound 2 in 30% yield. Subsequently, heating 2 in toluene under refluxing temperature rendered the title compound quantitatively. The structure of this tricyclic-fused compound was characterized using NMR, mass spectroscopy, and X-ray crystallography. This unique linear tricyclic fused furan framework is reported for the first time. Full article

Isatropolone C from Streptomyces sp. CPCC 204095 features a fused cyclopentadienone-tropolone-oxacyclohexadiene tricyclic moiety in its structure. Herein, we report an isatropolone C dimer derivative, di-isatropolone C, formed spontaneously from isatropolone C in methanol. Notably, the structure of di-isatropolone C resolved by NMR reveals a newly formed cyclopentane ring to associate the two isatropolone C monomers. The configurations of four chiral carbons, including a ketal one, in the cyclopentane ring are assigned using quantum NMR calculations and DP4+ probability. The plausible molecular mechanism for di-isatropolone C formation is proposed, in which complex dehydrogenative C-C bond coupling may have happened to connect the two isatropolone C monomers. Like isatropolone C, di-isatropolone C shows the biological activity of inducing autophagy in HepG2 cells. Full article

A practical metal-free and additive-free approach for the synthesis of 6/7/8-membered oxacyclic ketone-fused isoxazoles/isoxazolines tetracyclic or tricyclic structures is reported through C_sp³–H bond radical nitrile oxidation and the intramolecular cycloaddition of alkenyl/alkynyl-substituted aryl methyl ketones. This convenient approach enables the simultaneous formation of isoxazole/isoxazoline and 6/7/8-membered oxacyclic ketones to form polycyclic architectures by using tert-butyl nitrite (TBN) as a non-metallic radical initiator and N–O fragment donor. Full article

We theoretically investigated the nitrogen substitution effect on the molecular structure and π-electron delocalization in linear nitrogen-substituted polycyclic aromatic hydrocarbons (N-PAHs). Based on the optimized molecular structures and magnetic field-induced parameters of fused bi- and tricyclic linear N-PAHs, we found that the local π-electron delocalization of subcycles (e.g., mono- and bicyclic constituent moieties) in linear N-PAHs is preserved, despite deviation from ideal structures of parent monocycles. The introduction of a fused five-membered ring with a pyrrolic N atom (N-5MR) in linear N-PAHs significantly perturbs the π-electronic condition of the neighboring fused six-membered ring (6MR). Monocyclic pyrrole exhibits substantial bond length alternations, strongly influencing the π-electronic systems of both the fused N-5MR and 6MR in linear N-PAHs, depending on the location of shared covalent bonds. A fused six-membered ring with a graphitic N atom in an indolizine moiety cannot generate monocyclic π-electron delocalization but instead contributes to the formation of polycyclic π-electron delocalization. This is evidenced by bifurcated diatropic ring currents induced by an external magnetic field. In conclusion, the satisfaction of Hückel’s 4n + 2 rule for both mono- and polycycles is crucial for understanding the overall π-electron delocalization. It is crucial to consider the unique characteristics of the three types of substituted N atoms and the spatial arrangement of 5MR and 6MR in N-PAHs. Full article

Access to complex three-dimensional molecular architectures via dearomatization of ubiquitous aryl rings is a powerful synthetic tool, which faces, however, an inherent challenge to overcome energetic costs due to the loss of aromatic stabilization energy. Photochemical methods that allow one to populate high-energy states can thus be an ideal strategy to accomplish otherwise prohibitive reaction pathways. We present an original dearomative rearrangement of heteroaryl acryloylallenamides that leads to complex fused tricycles. The visible-light-promoted method occurs under mild conditions and tolerates a variety of functional groups. According to DFT modeling used to rationalize the outcome of the cascade, the reaction involves a sequential [2+2] allene–alkene photocycloaddition, which is followed by a selective retro- [2+2] step that paves the way for the dearomatization of the heteroaryl partner. This scenario is original with respect to the reported photochemical reactivity of similar substrates and thus holds promise for ample future developments. Full article

The innovative synthesis of 3,8-dibromo-2,9-dinitro-5,6-dihydrodiimidazo [1,2-a:2′,1′-c]pyrazine and 3,9-dibromo-2,10-dinitro-6,7-dihydro-5H-diimidazo [1,2-a:2′,1′-c][1,4]diazepine is described in this study. The tricyclic fused molecular structures are formed by the respective amalgamation of piperazine and homopiperazine with the imidazole ring containing nitro. Compound 1 and 2 possess excellent high-density physical properties (ρ₁ = 2.49 g/cm³, ρ₂ = 2.35 g/cm³) due to the presence of a fused ring structure and Br atom. In addition to their high density, they have high decomposition temperatures (T_d > 290 °C) which means that they have excellent thermal stability and can be used as potential heat-resistant explosives. Low mechanical sensitivities (IS > 40 J, FS > 360 N) are observed. The twinning structure of 2 was resolved by X-ray diffraction. Non-covalent interaction analysis, Hirshfeld surfaces, 2D fingerprint plot, and Electrostatic potential analysis were used to understand the intramolecular interactions in relation to physicochemical properties. The unique structures of this type of compound provide new potential for the evolution of energetic materials. Full article

A new series of trifluoromethylated pyrimido[1,2-b]indazol-4(1H)-one derivatives was synthesized with good to excellent yields through a simple condensation of 3-aminoindazole derivatives with ethyl 4,4,4-trifluoro 3-oxobutanoate. The functionalization of the corresponding chlorinated fused tricyclic scaffolds via Suzuki-Miyaura and aromatic nucleophilic substitution reactions led to the synthesis of highly diverse trifluoromethylated pyrimido[1,2-b]indazole derivatives with good yields. Full article

Lysimachia foenum-graecum Hance (Primulaceae) is a medicinal plant used for cold, pain, ascariasis, etc., in China. Triterpenoid saponins have been found to be the main components of this genus. In this work, a pair of oleanane-type triterpenoid saponins with an unprecedented 4/5/6 fused tricyclic skeleton, foegraecumoside O (1) and foegraecumoside P (2) were isolated from the butanol fraction of the aerial parts of L. foenum-graecum. Their structures were determined using chemical methods and extensive spectroscopic analyses, along with quantum chemical calculations. Compound 2 displayed moderate cytotoxicity against HepG2, MGC-803, T24, NCI-H460, A549, and A549/CDDP (drug-resistant lung-cancer cell line) with IC₅₀ at 12.4–19.2 μM in an MTT assay, comparing with the positive control doxorubicin, which had IC₅₀ at 0.53–4.92 μM, but was inactive for A549/CDDP. Furthermore, a possible biosynthetic pathway for forming compounds 1 and 2 was proposed. Full article

A practical method was developed for the convenient synthesis of isoxazole-fused tricyclic quinazoline alkaloids. This procedure accesses diverse isoxazole-fused tricyclic quinazoline alkaloids and their derivatives via intramolecular cycloaddition of methyl azaarenes with tert-butyl nitrite (TBN). In this method, TBN acts as the radical initiator and the source of N–O. Moreover, this protocol forms new C–N, C–C, and C–O bonds via sequence nitration and annulation in a one-pot process with broad substrate scope and functionalization of natural products. Full article