Synthesis Of Rings Research Articles

Ring Expansion Reactions via C-N Bond Cleavage in the Synthesis of Medium-sized Cycles and Macrocycles

The literature review discusses and systematizes synthetic approaches to medium-sized cycles and macrocycles based on ring expansion reactions of bi- or polycyclic systems via C-N bond cleavage. Ring expansion reactions of bicyclic ammonium salts proceed via thermal decomposition or the action of strong bases. Bi- or polycyclic systems containing a common amine group can be reduced with strong reducing reagents, e.g. lithium aluminum hydride. Ammonium derivatives are much more prone to nucleophilic attack and quite often are used as starting materials for the synthesis of medium-sized cycles. Bicyclic systems containing a common aminal or amidine group are used for the synthesis of medium-sized rings and macrocycles via cleavage of the endocyclic C-N bond. Various methods of their activation and reduction are discussed in the review.

The Synthesis, Structure, and Supramolecular Chemistry of Anthracene Rings and Cages

The Synthesis, Structure, and Supramolecular Chemistry of Anthracene Rings and Cages

Phosphetene-Based Polyaromatics: Structure-Property Relationships and Chiroptical Tuning.

We describe the synthesis of π-extended phosphetene rings (4-member P-rings) flanked with PAH systems of various topologies. These compounds are fully characterized including X-ray diffraction. The impact of both the polyaromatic platform and the P-ring on the structure, and the optical and redox properties are investigated both experimentally and theoretically. Although neither the P centre nor the 4-membered ring significantly takes part in the HOMO or LUMO orbitals, both structural features have an important modulating role in distorting the symmetry of the orbitals, leading to chiroptical properties. The stereogenic P-atom is used as a remote chiral perturbator to induce circularly polarized luminescence of the polyaromatic system. The dissymmetry factor is highly dependent on the polyaromatic topology, as supported by theoretical calculations.

Polyketide Origin of the Indole Ring during the Biosynthesis of Indole Alkaloid Coprisidins.

Coprisidins, a new class of indole alkaloids, feature a 1,4-naphthoquinone moiety attached to C-3 of 2-oxindole. Heterologous expression of a type II polyketide synthase-containing gene cluster resulted in the generation of three coprisidins. Gene disruption and isotope feeding studies suggested that the 2-oxindole moieties of coprisidins originate from a tetracyclic aromatic polyketide through oxidative rearrangements. This represents a novel biosynthetic route for the synthesis of indole rings in nature.

Unified Synthesis of NOPQ and STUV Rings of Brevisulcenal-F

Abstract The unified synthesis of the NOPQ and STUV rings of brevisulcenal-F was achieved from a common intermediate based on a convergent strategy via two-ring construction. The STUV ring was synthesized via radical reduction of an O, S-acetal, and the NOPQ ring was constructed via ring expansion giving a seven-membered ring ketone, methylation of an O, S-acetal, and introduction of the cis-1,2-diol moiety at C60–C61.

Visible light-induced pericyclic cascade reaction for the synthesis of eight-membered rings

A visible light-induced pericyclic cascade reaction for the synthesis of eight-membered rings is described. The reaction proceeds via [2 + 2]-photocycloaddition, base-promoted elimination, and retro-4π-electrocyclization. It exhibits broad substrate scope and good functional group tolerance.

Designed Synthesis of an Aluminum Molecular Ring Based Rotaxane and Polyrotaxane.

Mechanically interlocked molecules, such as rotaxanes, have drawn significant attention within supramolecular chemistry. Although a variety of macrocycles have been thoroughly explored in rotaxane synthesis, metal-organic macrocycles remain relatively under-investigated. Aluminum molecular rings, with their inner cavities and numerous binding sites, present a promising option for constructing rotaxanes. Here, we introduce an innovative "ring-donor⋅⋅⋅axle-acceptor" motif utilizing Al8 molecular rings, enabling the stepwise assembly of molecules, complexes, and polymers through tailored coordination chemistry. This novel approach can not only be applied to macrocycle-based systems like catenanes but also enhance specific functionalities progressively.

Enantioselective Nickel-Catalyzed α-Spirocyclization of Lactones.

Herein we report a strategy for the enantioselective synthesis of spirocycles containing all-carbon quaternary centers via nickel-catalyzed intramolecular addition of lactone enolates to aryl nitriles. The established lactone α-spirocyclization efficiently and enantioselectively forges 5-, 6-, and 7-membered rings, performing best in the synthesis of 7-membered rings (up to 90% ee). This discovery represents an expansion of the synthetic toolkit for enantioselective spirocyclization, providing access to chiral, pharmaceutically relevant spirocyclic products.

Synthesis of Oxa-bridged Medium-Sized Carbocyclic Rings

Abstract: Natural products with oxa-bridged medium-sized carbocyclic ring structure units play an important role in nature. Therefore, developing novel and efficient methods is essential for synthesizing complex natural products containing oxygen-bridged rings. In this article, progress toward the synthesis of oxygen-bridged seven and eight-membered rings is reviewed in terms of the strategies employed.

Modular and Regioselective Synthesis of Benzo-Fused Five-Membered Rings Enabled by Co/Ti Synergism.

The regiocontrol in constructing benzo-fused five-membered rings by C-H cyclization remains an important challenge. We report a highly general and regioselective methodology to access such heterocycles and indenones, where under the catalysis of CoBr2/bipyridine, aryl titanates, alkynes and EX2 (E = NR, S(O), RP(O), R2Si, CO, etc.) were assembled to various heterocycles and indenones in a modular manner. Unprecedented 1,2-Co/Ti heterobimetallic arylene and benzotitanole intermediates have played crucial roles in these syntheses.

Designed Synthesis of an Aluminum Molecular Ring Based Rotaxane and Polyrotaxane

Mechanically interlocked molecules, such as rotaxanes, have drawn significant attention within supramolecular chemistry. Although a variety of macrocycles have been thoroughly explored in rotaxane synthesis, metal‐organic macrocycles remain relatively under‐investigated. Aluminum molecular rings, with their inner cavities and numerous binding sites, present a promising option for constructing rotaxanes. Here, we introduce an innovative "ring‐donor···axle‐acceptor" motif utilizing Al8 molecular rings, enabling the stepwise assembly of molecules, complexes, and polymers through tailored coordination chemistry. This novel approach can not only be applied to macrocycle‐based systems like catenanes but also enhance specific functionalities progressively.

Transition metal complexes of hydrazones as potential antimicrobial and anticancer agents: A short review.

Hydrazones display an interesting profile of biological activities, which includes mainly antimicrobial and antiproliferative properties. Hydrazones also play an important role in the synthesis of heterocyclic rings and in coordination chemistry. Currently, the synthesis of complexes of hydrazones with transition metals is quite frequently reported in the scientific literature. The interest in this topic is largely due to diverse biological activities of the metal complexes of hydrazones that in some cases are much more effective than hydrazones themselves. This review focuses on the complexes of hydrazones with transition metals which display antibacterial, antitubercular, antifungal and anticancer activities. In the following subchapters devoted to a given activity, an attempt has been made to present the most active complexes of hydrazones, their trends in their activity and application in medicinal chemistry. The paper presents the literature data from 2009 to 2023. This review constitutes a useful guide for the researchers who intend to synthesize and investigate complexes of hydrazones in terms of their antimicrobial and anticancer activities.

Design Synthesis and Spectral Characterization of Novel Morpholine ring fused with Substituted Pyrazoline Derivatives as Promising Anticancer, Antimicrobial Activity of in vitro and in silico studies

A search for new anticancer agents has prompted the design and synthesis of new novel morpholine ring fused with substituted pyrazoline derivatives MCP 1-4 as potent anticancer agents. MCP compounds were synthesized and the compounds structures were elucidated using elemental analysis and spectroscopic techniques like FT-IR, 1H NMR and 13C NMR. MCP derivatives binding affinities values were predicted by Auto Dock version, which shows the MCP derivatives as good anticancer 1OQA protein and antimicrobial properties, bacterial protein 1UAG and 5KEE with good binding affinity values from -6.2 to -6.5 kcal/mole and -7.6 to -8.9 kcal/ mole respectively. Among the four MCP compounds, the compounds MCP-1,3 and 4 have the similar binding interaction values of 6.5 kcal/mole. The MCP derivatives have good virus inhibition activity and these compounds are docked with SARS COVID 19 CORONA virus protein 6LU7 to have the docking score values -7.4 to 7-7.6 kcal/ mole. In silico ADME predictions were carried for the synthesized MCP 1-4 derivatives by online tool Swissadme. MCP derivatives have the good log p value of <5. MCP derivatives were also evaluated by antimicrobial activity, the compound MCP-3 showed zone of inhibition values on all the sixteen bacterial cell lines. The compound MCP-3 was subjected to anticancer screening on MCF-7 cell line, the compound showed the good IC50 value.

Efficient and green synthesis of 2,3-benzofuran via gas–solid catalytic route

Biologically active molecule 2,3-benzofuran is an important category of heterocyclic compounds for pharmacological agents, which is usually produced via multistep organic synthesis routes under acidic, alkaline, or halogen conditions. It remains a challenge to develop a green approach for the production of 2,3-benzofuran. Herein, we report an unprecedent green synthesis of 2,3-benzofuran with co-production of styrene in the selective oxidation of ethylbenzene reaction over Sr2+ modified FeOx/SiO2 catalyst. Characterizations with O2-TPD, UV–Vis, XANES, and XRD demonstrate that the addition of Sr2+ increased the content of adsorbed oxygen and dispersion of the iron species. Kinetic investigations and DFT calculations reveal that firstly ethylbenzene reacted with oxygen adsorbed on the Fe3+ species to form the intermediate 2-ethylphenol, followed by selective oxidation of 2-ethylphenol to efficiently generate 2,3-benzofuran. These discoveries present an efficient pathway to produce 2,3-benzofuran and offer novel insights into the synthesis of furan rings, thereby contributing to advancement in chemical synthesis processes.

Aluminum Molecular Ring Meets Deep Eutectic Solvents: Adaptive Assembly and Optical Behavior.

Different from the previous neutral reaction solvent system, this work explores the synthesis of Al-oxo rings in ionic environments. Deep eutectic solvents (DESs) formed by quaternary ammonium salts hydrogen bond acceptor (HBA) and phenols hydrogen bond donor (HBD) further reduce the melting point of the reaction system and provide an ionic environment. Further, the quaternary ammonium salt was chosen as the HBA because it contains a halogen anion that matches the size of the central cavity of the molecular ring. Based on this thought, five Al8 ion pair cocrystals were synthesized via "DES thermal". The general formula is Q+ ⊂ {Cl@[Al8(BD)8(μ2-OH)4L12]} (AlOC-180-AlOC-185, Q+ = tetrabutylammonium, tetrapropylammonium, 1-butyl-3-methylimidazole; HBD = phenol, p-chlorophenol, p-fluorophenol; HL = benzoic acid, 1-naphthoic acid, 1-pyrenecarboxylic acid, anthracene-9-carboxylic acid). Structural studies reveal that the phenol-coordinated Al molecular ring and the quaternary ammonium ion pair form the cocrystal compounds. The halogen anions in the DES component are confined in the center of the molecular ring, and the quaternary ammonium cations are located in the organic shell. Such an adaptive cocrystal binding pattern is particularly evident in the structures coordinated with low-symmetry ligands such as naphthoic acid and pyrene acid. Finally, the optical behavior of these cocrystal compounds is understood from the analysis of crystal structure and theoretical calculation.

Enantioselective Synthesis of Oxazocines via MQ-Phos Enabled Palladium-Catalyzed Asymmetric Formal [4+4]-Cycloadditions.

Oxazocines are key structural intermediates in the synthesis of natural products and pharmaceutical molecules. However, the synthesis of oxazocines especially in a highly enantioselective manner, is a long-standing formidable challenge due to unfavorable energetics involved in cyclization. Herein, a series of new PNP-Ligand P-chiral stereocenter is first designed and synthesized, called MQ-Phos, and successfully applied it in the Pd-catalyzed enantioselective higher-order formal [4+4]-cycloaddition of α, β-unsaturated imines with 2-(hydroxymethyl)-1-arylallyl carbonates. The reaction features mild conditions, excellent regio- and enantiocontrol and a broad substrate scope (54 examples). Various medium-sized rings can be afforded in moderate to excellent yields (up to 92%) and excellent enantioselectivity (up to 99% ee). The newly developed MQ-Phos is critical for synthesis of the medium-sized ring in excellent catalytic reactivity and enantioselectivity.

Synthesis and Urease Inhibition Activities of Some New Schiff Bases Benzimidazoles Containing Thiophene Ring

Synthesis and Urease Inhibition Activities of Some New Schiff Bases Benzimidazoles Containing Thiophene Ring

Click chemistry beyond metal-catalyzed cycloaddition as a remarkable tool for green chemical synthesis of antifungal medications.

Click chemistry is widely used for the efficient synthesis of 1,4-disubstituted-1,2,3-triazole, a well-known scaffold with widespread biological activity in the pharmaceutical sciences. In recent years, this magic ring has attracted the attention of scientists for its potential in designing and synthesizing new antifungal agents. Despite scientific and medical advances, fungal infections still account for more than 1.5 million deaths globally per year, especially in people with compromised immune function. This increasing trend is definitely related to a raise in the incidence of fungal infections and prevalence of antifungal drug resistance. In this condition, an urgent need for new alternative antifungals is undeniable. By focusing on the main aspects of reaction conditions in click chemistry, this review was conducted to classify antifungal 1,4-disubstituted-1,2,3-triazole hybrids based on their chemical structures and introduce the most effective triazole antifungal derivatives. It was notable that in all reactions studied, Cu(I) catalysts generated insitu by the reduction in Cu(II) salts or used copper(I) salts directly, as well as mixed solvents of t-BuOH/H2O and DMF/H2O had most application in the synthesis of triazole ring. The most effective antifungal activity was also observed in fluconazole analogs containing 1,2,3-triazole moiety and benzo-fused five/six-membered heterocyclic conjugates with a 1,2,3-triazole ring, even with better activity than fluconazole. The findings of structure-activity relationship and molecular docking of antifungal derivatives synthesized with copper-catalyzed azide-alkyne cycloaddition (CuAAC) could offer medicinal chemistry scientists valuable data on designing and synthesizing novel triazole antifungals with more potent biological activities in their future research.

Theoretical study of [3 + 3] annulation reaction of bromoenal with β-tetralone catalysed by N-heterocyclic carbene

N-heterocyclic carbenes (NHCs) are effective organocatalysts, which are widely used in various cycloaddition reactions. Among them, the [3 + 3] cycloaddition reaction type can be used for the synthesis of six-membered ring, which is also one of the most important methods for the formation of carbon–carbon bonds in organic chemistry. In this paper, a possible reaction pathway for the stereoselective [3 + 3] cycloaddition of bromoenal and β-tetralone have been investigated at the M06-2X/6–31G(d,p)/IEFPCM(THF) level. Our suggested mechanism includes binding of the NHC to bromoenal, 1,2-proton transfer, debromination, 1,3-proton shift, Michael addition, protonation, deprotonation and cyclisation, and NHC regeneration. The stereochemistry of the reaction is determined by the Michael addition step, and the favourable pathway generates the R-configurational dihydropyranone. Furthermore, through the use of global reactivity indexes (GRIs), we are able to demonstrate that the nucleophilicity of the bromoenal is increased by the NHC. The mechanistic insights gained in this work should be helpful in the rational design of potential catalysts for analogous reactions.

SYNTHESIS OF NEW γ-LACTONE RING DERIVATIVES CONTAINING PYRIDINE AND TRICONDENSED SYSTEMS

Lactone-pyridone rings contain many biologically active molecules of natural and artificial origin. The molecules contained in these two rings, represented by Cerpegine and its derivatives, will also exhibit high biological activity. It is also necessary to take into account that both natural and synthetic multi-substituted lactones have high biological activity. Thus, research in the field of multi-substituted lactones and further transformations are of particular interest. The synthesis of such systems began with the synthesis of a 2-acetylfuranone ring. In the next step, condensation of ethylcyanoacetate with 2-acetylfuranone by Knewenegel produced 3-substituted lactones, which according to the NMP 1H spectroscopy are a mixture of E and Z isomers. Then, when 3-substituted lactones were heated with dimethylformamide dimethylacetal DMFA/DMA, 3-substituted lactones containing a diene fragment in the structure were obtained. Stereoselective attachment E was detected using the NMR 1H spectrum. Then, under the action of the corresponding amine, the intermolecular substitution reactions produce compounds containing a lactone and pyridine group isolated by a σ-bond (serpegenous compound). Due to the proximity of the cyanide group of the pyridine ring and the fourth blight group of the lactone ring, intramolecular cyclization occurs during heating in the alkaline medium to form new tricondensed systems. Thus, an optimal method of synthesis of serpegenous compounds has been developed. These systems are of interest because in their skeleton they have not only a condensed system but also spirocycles. The connections themselves may be a promise for further exploration. For citation: Hakobyan R.M., Kharatyan L.A., Hayotsyan S.S., Attaryan H.S., Melikyan G.S. Synthesis of new γ-lactone ring derivatives containing pyridine and tricondensed systems. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 7. P. 28-40. DOI: 10.6060/ivkkt.20246707.7068.