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The metathesis reaction between carbonyl compounds and olefins has emerged as a potent strategy for facilitating swift functional group interconversion and the construction of intricate organic structures through the creation of novel carbon–carbon double bonds. To date, significant progress has been made in carbonyl–olefin metathesis reactions, where oxetane, pyrazolidine, 1,3-diol, and metal alkylidene have been proved to be key intermediates. Recently, several reviews have been disclosed, focusing on distinct catalytic approaches for achieving carbonyl–olefin metathesis. However, the summarization of cyclization strategies for constructing aromatic heterocyclic frameworks through carbonyl–olefin metathesis reactions has rarely been reported. Consequently, we present an up-to-date review of the cyclization strategies in carbonyl–olefin metathesis, categorizing them into three main groups: the formation of monocyclic compounds, bicyclic compounds, and polycyclic compounds. This review delves into the underlying mechanism, scope, and applications, offering a comprehensive perspective on the current strength and the limitation of this field. [ABSTRACT FROM AUTHOR]

Palladium‐catalyzed bicyclization of 1‐(2,2‐dibromovinyl)‐2‐alkenylbenzene with allenyl malonates has been achieved to afford a series of bicyclic compounds. The protocol involves intermolecular carbopalladation of allenes/cyclization/internal Heck reaction. Three C−C bonds and two rings are formed in one step. [ABSTRACT FROM AUTHOR]

Modular synthesis can combine different functional modules to flexibly regulate comprehensive properties and study the diversity of compounds. This study established a modular bicyclic synthesis strategy of combining polynitro energetic module with iodine‐containing biocidal module. Compounds 1–6 with high iodine content (48.72–69.56 %) and high thermal stability (Td: 172–304 °C) were synthesized and exhaustively identified. By modular synthesis, the detonation properties and gas‐production of 3–6 improved greatly expanding their biocidal efficacy and maintained the iodine atomic utilization of iodine‐containing module. Notably, 4,5‐diiodo‐3,4',5'‐trinitro‐1,3'‐bipyrazole (5) and 3,5‐diiodo‐4,4',5'‐trinitro‐1,3'‐bipyrazole (6) exhibit high detonation velocities (D: 5903 m s−1, 5769 m s−1, respectively) and highest gas production of 212.85 L mol−1 and 217.66 L mol−1 after decomposition. This study diversifies polyiodio‐nitro compounds, and also inspire the implementation of similar synthesis strategies to provide family‐level synthetic solutions to energetic biocidal materials. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a widespread global epidemic that affects individuals across all age groups and presents a significant public health challenge. Comprising various cardio-metabolic risk factors, MetS contributes to morbidity and, when inadequately addressed, can lead to mortality. Current therapeutic approaches involve lifestyle changes and the prolonged use of pharmacological agents targeting the individual components of MetS, posing challenges related to cost, compliance with medications, and cumulative side effects. To overcome the challenges associated with these conventional treatments, herbal medicines and phytochemicals have been explored and proven to be holistic complements/alternatives in the management of MetS. Thymoquinone (TQ), a prominent bicyclic aromatic compound derived from Nigella sativa emerges as a promising candidate that has demonstrated beneficial effects in the treatment of the different components of MetS, with a good safety profile. For methodology, literature searches were conducted using PubMed and Google Scholar for relevant studies until December 2023. Using Boolean Operators, TQ and the individual components of MetS were queried against the databases. The retrieved articles were screened for eligibility. As a result, we provide a comprehensive overview of the anti-obesity, anti-dyslipidaemic, anti-hypertensive, and anti-diabetic effects of TQ including some underlying mechanisms of action such as modulating the expression of several metabolic target genes to promote metabolic health. The review advocates for a paradigm shift in MetS management, it contributes valuable insights into the multifaceted aspects of the application of TQ, fostering an understanding of its role in mitigating the global burden of MetS. [ABSTRACT FROM AUTHOR]

The synthesis and biosynthesis of the complex saxitoxin (STX) structure have garnered significant interest. Previously, we hypothesized that the tricyclic skeleton of STX originates from the monocyclic precursor 11‐hydroxy‐IntC’2 during biosynthesis, although direct evidence has been lacking. In this study, we identified conditions to synthesize a proposed tricyclic biosynthetic intermediate, 12,12‐dideoxy‐decarbamoyloxySTX (dd‐doSTX), along with its 6‐epimer (6‐epi‐dd‐doSTX) and a bicyclic compound, in a single step from di‐Boc protected 11‐hydroxy‐IntC’2. The reaction mechanism involves successive aza‐Michael addition of a guanidino amine to the conjugated olefin. Notably, both dd‐doSTX and 6‐epi‐dd‐doSTX were detected in a toxin‐producing cyanobacterium, suggesting that the biosynthetic enzymes may generate these compounds via similar mechanisms. [ABSTRACT FROM AUTHOR]

Bridgehead alkenes are polycyclic molecules bearing at least one C=C bond that includes a bridgehead carbon atom. For small bicyclic systems, these bonds are highly strained due to geometric constraints placed on the sp2 hybridized carbon atoms. These small, strained molecules have been termed "anti-Bredt" alkenes. β-halo carbanions have served as convenient precursors to bridgehead alkenes in experimental studies. We observed that upon attempted computational geometric optimizations (ωB97X-D/aug-cc-pVDZ) of the precursors, spontaneous elimination of the halide occurs along with formation of the anti-Bredt alkene in many cases. Such computational eliminations were shown to faithfully mimic experimentally obtained results. Computational elimination was not observed for [1.1.1] or [2.1.1] frameworks, in agreement with predictions that these bridgehead alkenes are too strained to be formed. However, computational elimination from the [2.2.1] framework was observed to form 1-norbornene, a compound suggested in experimental work to be a reactive intermediate. Similarly, [3.1.1] frameworks and higher led to eliminations upon computational geometric optimization, in agreement with experimental findings. Natural bond order (NBO) calculations of the starting geometries proved to be excellent predictors as to whether elimination would take place. Those precursor compounds exhibiting delocalization energies in the order of 10 kcal/mol between the lone-pair electrons of the carbon atom and σ*C-Br were generally found to undergo elimination. Thus, computational optimization of β-halo substituted bicyclic precursor anions can be used to predict whether strained anti-Bredt alkenes are likely to be formed, thereby saving valuable time and costs in the experimental lab. [ABSTRACT FROM AUTHOR]

Fused bicyclic cyclopropanes were converted by Lewis acid‐catalysis with thioureas to furo‐, pyrano, and pyrrololactams with yields of up to 99 % and high diastereoselectivity. The formation of the title compounds, representing a formal [4+1]‐cycloaddition to a donor‐acceptor substituted cyclopropane, follows a cascade reaction involving SN1‐type ring‐opening addition and cyclization. Thiourea, being a cost‐effective and odorless reagent, acts as an N,N‐bis‐nucleophile to generate bicyclic compounds containing an N‐substituted γ‐lactam moiety. [ABSTRACT FROM AUTHOR]

Currently, antimicrobial resistance (AMR) is a serious health problem in the world, mainly because of the rapid spread of multidrug-resistant (MDR) bacteria. These include bacteria that produce β-lactamases, which confer resistance to β-lactams, the antibiotics with the most prescriptions in the world. Carbapenems are particularly noteworthy because they are considered the ultimate therapeutic option for MDR bacteria. However, this group of antibiotics can also be hydrolyzed by β-lactamases, including metallo-β-lactamases (MBLs), which have one or two zinc ions (Zn2+) on the active site and are resistant to common inhibitors of serine β-lactamases, such as clavulanic acid, sulbactam, tazobactam, and avibactam. Therefore, the design of inhibitors against MBLs has been directed toward various compounds, with groups such as nitrogen, thiols, and metal-binding carboxylates, or compounds such as bicyclic boronates that mimic hydrolysis intermediates. Other compounds, such as dipicolinic acid and aspergillomarasmin A, have also been shown to inhibit MBLs by chelating Zn2+. In fact, recent inhibitors are based on Zn2+ chelation, which is an important factor in the mechanism of action of most MBL inhibitors. Therefore, in this review, we analyzed the current strategies for the design and mechanism of action of metal-ion-binding inhibitors that combat MDR bacteria. [ABSTRACT FROM AUTHOR]

Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential to mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf)3‐catalyzed [3+2] cycloaddition of bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding a diverse array of polysubstituted 2‐amino‐bicyclo[2.1.1]hexenes in good to excellent yields. These products offer valuable starting materials for the construction of novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that the reaction involves a nucleophilic addition of ynamides to bicyclo[1.1.0]butanes, followed by an intramolecular cyclization of in situ generated enolate and keteniminium ion. We expect that these findings will encourage utilization of complex bioisosteres and foster further investigation into BCB‐based cycloaddition chemistry. [ABSTRACT FROM AUTHOR]

The exploration of the complex chemical diversity of bicyclo[n.1.1]alkanes and their use as benzene bioisosteres has garnered significant attention over the past two decades. Regiodivergent syntheses of thiabicyclo[4.1.1]octanes (S‐BCOs) and highly substituted bicyclo[2.1.1]hexanes (BCHs) using a Lewis acid‐catalyzed formal cycloaddition of bicyclobutanes (BCBs) and 3‐benzylideneindoline‐2‐thione derivatives have been established. The first hetero‐(4+3) cycloaddition of BCBs, catalyzed by Zn(OTf)2, was achieved with a broad substrate scope under mild conditions. In contrast, the less electrophilic BCB ester undergoes a Sc(OTf)3‐catalyzed [2π+2σ] reaction with 1,1,2‐trisubstituted alkenes, yielding BCHs with a spirocyclic quaternary carbon center. Control experiments and preliminary theoretical calculations suggest that the diastereoselective [2π+2σ] product formation may involve a concerted cycloaddition between a zwitterionic intermediate and E‐1,1,2‐trisubstituted alkenes. Additionally, the hetero‐(4+3) cycloaddition may involve a concerted nucleophilic ring‐opening mechanism. [ABSTRACT FROM AUTHOR]

Biofilm formation and surface attachment in multiple Alphaproteobacteria is driven by unipolar polysaccharide (UPP) adhesins. The pathogen Agrobacterium tumefaciens produces a UPP adhesin, which is regulated by the intracellular second messenger cyclic diguanylate monophosphate (c-di-GMP). Prior studies revealed that DcpA, a diguanylate cyclase-phosphodiesterase, is crucial in control of UPP production and surface attachment. DcpA is regulated by PruR, a protein with distant similarity to enzymatic domains known to coordinate the molybdopterin cofactor (MoCo). Pterins are bicyclic nitrogen-rich compounds, several of which are produced via a nonessential branch of the folate biosynthesis pathway, distinct from MoCo. The pterin-binding protein PruR controls DcpA activity, fostering c-di-GMP breakdown and dampening its synthesis. Pterins are excreted, and we report here that PruR associates with these metabolites in the periplasm, promoting interaction with the DcpA periplasmic domain. The pteridine reductase PruA, which reduces specific dihydro-pterin molecules to their tetrahydro forms, imparts control over DcpA activity through PruR. Tetrahydromonapterin preferentially associates with PruR relative to other related pterins, and the PruR-DcpA interaction is decreased in a pruA mutant. PruR and DcpA are encoded in an operon with wide conservation among diverse Proteobacteria including mammalian pathogens. Crystal structures reveal that PruR and several orthologs adopt a conserved fold, with a pterin-specific binding cleft that coordinates the bicyclic pterin ring. These findings define a pterin-responsive regulatory mechanism that controls biofilm formation and related c-di-GMP-dependent phenotypes in A. tumefaciens and potentially acts more widely in multiple proteobacterial lineages. [ABSTRACT FROM AUTHOR]

Synthesis of bicyclic scaffolds has emerged as an important research topic in modern drug development because they can serve as saturated bioisosters to enhance the physicochemical properties and metabolic profiles of drug candidates. Here we report a remarkably simple silver‐enabled strategy to access polysubstituted 3‐azabicyclo[3.1.1]heptanes in a single operation from readily accessible bicyclobutanes (BCBs) and isocyanides. The process is proposed to involve a formal (3+3)/(3+2)/retro‐(3+2) cycloaddition sequence. This novel protocol allows for rapid generation of molecular complexity from simple starting materials, and the products can be easily derivatized, further enriching the BCB cycloaddition chemistry and the growing set of valuable sp3‐rich bicyclic building blocks. [ABSTRACT FROM AUTHOR]

Herein, we have synthesized multifunctionalized 2‐oxa‐3‐azabicyclo[3.1.1]heptanes, which are considered potential bioisosteres for meta‐substituted arenes, through Eu(OTf)3‐catalyzed formal dipolar [4π+2σ] cycloaddition of bicyclo[1.1.0]butanes with nitrones. This methodology represents the initial instance of fabricating bicyclo[3.1.1]heptanes adorned with multiple heteroatoms. The protocol exhibits both mild reaction conditions and a good tolerance for various functional groups. Computational density functional theory calculations support that the reaction mechanism likely involves a nucleophilic addition of nitrones to bicyclo[1.1.0]butanes, succeeded by an intramolecular cyclization. The synthetic utility of this novel protocol has been demonstrated in the concise synthesis of the analogue of Rupatadine. [ABSTRACT FROM AUTHOR]

The metathesis reaction between carbonyl compounds and olefins has emerged as a potent strategy for facilitating swift functional group interconversion and the construction of intricate organic structures through the creation of novel carbon–carbon double bonds. To date, significant progress has been made in carbonyl–olefin metathesis reactions, where oxetane, pyrazolidine, 1,3-diol, and metal alkylidene have been proved to be key intermediates. Recently, several reviews have been disclosed, focusing on distinct catalytic approaches for achieving carbonyl–olefin metathesis. However, the summarization of cyclization strategies for constructing aromatic heterocyclic frameworks through carbonyl–olefin metathesis reactions has rarely been reported. Consequently, we present an up-to-date review of the cyclization strategies in carbonyl–olefin metathesis, categorizing them into three main groups: the formation of monocyclic compounds, bicyclic compounds, and polycyclic compounds. This review delves into the underlying mechanism, scope, and applications, offering a comprehensive perspective on the current strength and the limitation of this field.

Electrophilic double bond functionalization – intramolecular enolate alkylation sequence was used to obtain a series of bridged and fused bicyclo[m.n.k]alkane derivatives (i. e., bicyclo[4.1.1]octanes, bicyclo[2.2.1]heptanes, bicyclo[3.2.1]octanes, bicyclo[3.1.0]hexanes, and bicyclo[4.2.0]heptanes). The scope and limitations of the method were established, and applicability to the multigram synthesis of target bicyclic compounds was illustrated. Using the developed protocols, over 50 mono‐ and bifunctional building blocks relevant to medicinal chemistry were prepared. The synthesized compounds are promising isosteres of benzene and cycloalkane rings, which is confirmed by their physicochemical and structural characterization (pKa, LogP, and exit vector parameters (EVP)). "Rules of thumb" for the upcoming isosteric replacement studies were proposed. [ABSTRACT FROM AUTHOR]

Scalable [3+2] cycloaddition of alkynyl boronates and in situ generated unstabilized azomethine ylide is reported for the first time. The selective formation of either 1 : 1 or 1 : 2 cycloaddition products was achieved by carefully optimizing the reaction conditions, mainly by controlling the reactant stoichiometry, catalyst loading, and internal temperature. The developed protocol tolerated many valuable functional groups, including TMS, protected alcohol (as ether or THP derivatives), or aldehyde (as acetal). Further common C−C and C−heteroatom bond‐forming reactions, as well as scaled‐up procedures demonstrate the utility of the prepared compounds as building blocks for organic synthesis and drug discovery. [ABSTRACT FROM AUTHOR]

We report the Ni‐catalyzed cycloisomerization of 1,5‐allenynes. Substrates containing terminal alkynes afford cyclopentene derivatives, whereas internal alkynes lead to the formation of two consecutive C−C bonds to give fused 5–5 bicyclic compounds. The reaction shows a wide scope. Experimental and computational mechanistic studies suggest a Ni(0)−Ni(II) catalytic cycle. The reaction starts with an oxidative cyclometallation followed by a β‐hydrogen elimination. The trans arrangement of alkenyl and hydride ligands is key to allow formation of the second carbocycle. [ABSTRACT FROM AUTHOR]

An approach to gem‐difluoro‐3‐azabicyclo[3.n.1]alkane‐ derived building blocks through double‐Mannich addition– deoxofluorination sequence is described. The scope of the method was demonstrated for a series of saturated (hetero)cyclic ketones or ketoesters (including five‐ to seven‐membered cycloalkane derivatives and N‐, O‐, S‐containing saturated heterocycles). Further transformations of functional groups produced various bifunctionalized difluorinated building blocks, namely, N‐protected aminoacids, mono‐N‐Boc‐protected diamines, and unprotected aminoalcohols in good to excellent overall yields. For the azabicyclo[3.3.1]alkane series, a potential for isosteric replacements is demonstrated by evaluation of the key physicochemical properties (i. e., pKa(H) and LogP). [ABSTRACT FROM AUTHOR]

A straightforward approach to α‐CF3‐substituted saturated bicyclic amines starting from commercially available compounds is proposed. The key steps include addition of the Ruppert‐Prakash reagent to imine moiety and AlMe3‐promoted intramolecular heterocyclization. The reaction sequence provides access to fluorine‐containing azabicyclo[n.2.1]alkane (n=1–3) or azabicyclo[2.2.2]octane derivatives in 10–42 % overall yield. The physicochemical properties of the prepared compounds or their model derivatives (i. e., pKa and LogP) were measured and compared to those for the parent monocyclic or non‐fluorinated saturated heterocycles. As expected, amine basicity was lowered considerably upon introduction of the CF3 group (ΔpKa≈4), while the lipophilicity increased (by ca. 0.5 LogP units). The summarized data provides a convenient guideline for application of the synthesized compounds in drug discovery programs. [ABSTRACT FROM AUTHOR]

An efficient approach to the synthesis of previously unreported azabicyclo[4.1.0]heptane‐derived building blocks is reported following the divergent strategy. The common synthetic precursor – tert‐butyl 6‐(hydroxymethyl)‐3‐azabicyclo[4.1.0]heptane‐3‐carboxylate was obtained in four steps with 38 % overall yield and was involved in short reaction sequences (1–3 steps) to provide the target bifunctional derivatives, including novel bicyclic N‐Boc protected γ‐amino acid. The described compounds are interesting in terms of lead‐likeness concepts, according to which the rigid 3D‐shaped and sp3‐enriched frameworks are among the most promising entry points for drug discovery projects. [ABSTRACT FROM AUTHOR]

Photolyses of trans‐Fe(CO)3(P((CH2)n)3P) (n=10 (a), 12 (b), 14 (c), 16 (d), 18 (e)) in the presence of PMe3 provide the first economical and scalable route to macrobicyclic dibridgehead diphosphines P((CH2)n)3P (1). These are isolated as mixtures of in,in/out,out isomers that equilibrate with degenerate in,out/out,in isomers at 150 °C via pyramidal inversion at phosphorus. For the entire series, VT 31P NMR data establish or bound Keq, rates, and activation parameters for a variety of phenomena, many of which involve homeomorphic isomerizations, topological processes by which certain molecules can turn themselves inside out (e. g. in,in⇌out,out). This provides the first detailed mapping of such trends in homologous series of aliphatic bicyclic compounds XE((CH2)n)3EX with any type of bridgehead. Isomeric diborane adducts 1 a,d ⋅ 2BH3 are also characterized. Crystal structures of out,out‐1 a and in,in‐1 a ⋅ 2BH3 aid isomer assignments and reveal unusual cage conformations. [ABSTRACT FROM AUTHOR]

The carbodiimide-mediated coupling of 4-cyanonicotinic acid with L-amino acid methyl esters takes place with the predominant formation of bicyclic compounds – methyl 2-(1-imino-3-oxo-1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)alkanoates, which are monoimino derivatives of 4-azaphthalimide. Under the action of hydroxylamine they undergo pyrrolidine cycle opening with the formation of pseudopeptides – coupling products of nicotinic acid with amino acid esters bearing an amidoxime function at position 4. [ABSTRACT FROM AUTHOR]

Terpene compounds in the lower layer of the atmosphere can contribute to environmental problems through the formation of particulate material known as secondary organic aerosol (SOA). A clear understanding of the formation and composition of these particles hinges on reliable thermodynamic data. Quick estimation of these physical properties is highly desired. While experimental methods require significant resources and time, the prediction of pure-component properties through group contributions is easily applicable and straightforward. The present study compares the experimental enthalpies of vaporization at 298.15 K for bicyclic terpenes and related substances derived from the gas chromatography technique with estimated values provided by three group contribution methods. A new group contribution model specifically designed for terpene compounds is introduced. Furthermore, this study reveals previously unreported values in the literature for the enthalpy of vaporization at 298.15 K and the normal boiling temperature of Thymol methyl ether, Fenchyl alcohol, and Bicyclo [4.1.0] heptane-7-carboxylic acid. [ABSTRACT FROM AUTHOR]

Bicyclo[2.1.1]hexanes (BCHs) are becoming ever more important in drug design and development as bridged scaffolds that provide underexplored chemical space, but are difficult to access. Here a silver‐catalyzed dearomative [2π+2σ] cycloaddition strategy for the synthesis of indoline fused BCHs from N‐unprotected indoles and bicyclobutane precursors is described. The strain‐release dearomative cycloaddition operates under mild conditions, tolerating a wide range of functional groups. It is capable of forming BCHs with up to four contiguous quaternary carbon centers, achieving yields of up to 99 %. In addition, a scale‐up experiment and the synthetic transformations of the cycloadducts further highlighted the synthetic utility. [ABSTRACT FROM AUTHOR]

BODIPYs are bicyclic aromatic compounds with unique spectroscopic, photophysical, and chemical properties. This study aimed to find BODIPYs with characteristics biocompatible with human cell lines for possible use as imaging agents. Six BODIPY derivatives were synthesised with groups linked to boron, fluorine, phenol, or catechol, resulting in compounds with different physicochemical characteristics. NMR, absorption, and emission spectroscopy and mass spectrometry were subsequently used to characterise them. Afterwards, the biocompatibility of these compounds was evaluated using MTT, SRB, and cellular uptake assays in A549 and H1299 cell lines. Furthermore, a haemolysis assay was performed on human blood cells. To summarise the main results, BODIPYs 1 to 4 showed considerable fluorescence. In contrast, BODIPYs 5 and 6 showed very weak fluorescence, which could be related to the presence of the catechol group and its quenching properties. Regarding biocompatibility, all compounds had metabolic activity and viability above 80% and 70%, respectively. BODIPYs 3 and 6 presented the most consistent data, demonstrating good uptake and, in general, haemolytic activity below 25%. In conclusion, the cytotoxic effects of the compounds were not considerable, and the presence of cyclic alkoxides in BODIPYs 3 and 6 may introduce exciting features that should be highlighted for dual imaging for BODIPY 3 due to its fluorescence or for radioactive labelling in the case of both BODIPYs. [ABSTRACT FROM AUTHOR]

Objective: In the present study, we describe a novel class of small‐molecule synthetic compounds that ameliorate seizure‐like behavior, using an electroshock assay to examine seizure duration in Caenorhabditis elegans. We also examine the hypothesis that these compounds, which we have called resveramorphs (RVMs), act by an irreversible binding mechanism. Methods: Our electroshock assay examines seizure duration in C. elegans and can be used as a drug‐screening platform for the identification of novel anti‐seizure agents. The use of C. elegans allows for a rapid and efficient method of drug screening that may take years in other higher‐order model organisms. A novel wash method, paired with our electroshock assay, allows us to discern differences in biological activity when the C. elegans are incubated in different drug solutions, to establish whether these compounds can be "washed" off. Results: One of the RVMs (RVM‐3), reported here for the first time, was found to be potent at picomolar concentrations. Insights also provided information on the potential mechanisms of action of this compound. Covalent binding is thought to provide a strong irreversible bond because of a change in structure between two of the novel RVMs described in this work. This was also discerned through the novel wash method paired with our electroshock assay. Significance: RVM‐3 was evaluated using our assay and found to possess anti‐seizure activity at picomolar concentrations. These insights also provide information on the potential mechanisms of action of these compounds, which may include covalent binding. This was also discerned through a novel wash method paired with our electroshock assay. [ABSTRACT FROM AUTHOR]

A method for obtaining bromine-containing bicyclic unsaturated polyesters by the interaction of 1,4,5,6,7,7-hexabromobicyclo-[2,2,1]-hept-5-ene-2,3-dicarboxylic acid anhydride, propanetriol and maleic anhydride was developed. It was found that unsaturated polyethers synthesized by a two-step method have a higher molecular weight (3130), density (1.461 g/cm3), viscosity (105 St) and ether number (400 ml KOH/g). It was found that the compositions of epoxy resin ED-20 with unsaturated polyether obtained by method III possess higher tensile strength (90 MPa), higher relative elongation (9%), higher Vicat resistance (2500C) than unmodified epoxy resin. It was shown that in comparison with pure epoxy resin ED-20, its composition with unsaturated polyester synthesized by method I and cured in the presence of polyethylene polyamine (ED-20: unsaturated polyester: polyethylene polyamine), has flame retardant properties, high tensile strength, higher relative elongation and thermal resistance by Vicat. The best results are achieved when the content of unsaturated polyester in the composition is 20%. [ABSTRACT FROM AUTHOR]

A readily prepared and functionalized vinylogous nucleophile has been explored and utilized to construct bridged bicyclic compounds. The corresponding cascade Michael/Henry reaction occurred with relatively high reactivity under catalyst‐free and mild conditions. A range of structurally distinct bicyclo[3.2.1]octanes were generated in 40–96% isolated yields with excellent diastereoselectivities (≥10:1 dr). Gram‐scale synthesis was also demonstrated. [ABSTRACT FROM AUTHOR]

The reaction of N-phenyl iminoborane with benzaldehyde yielding a fused aromatic compound, recently reported by Liu et al., has been studied within the Molecular Electron Density Theory (MEDT). Formation of the fused aromatic compound is a domino process that comprises three consecutive reactions: (i) formation of a weak molecular complex between the reagents; (ii) an intramolecular electrophilic attack of the activated carbonyl carbon of benzaldehyde on the ortho position of the N-phenyl substituent of iminoborane; and (iii) a formal 1,3-hydrogen shift yielding the final fused aromatic compound. The two last steps correspond to a Friedel–Crafts acylation reaction, the product of the second reaction being the tetrahedral intermediate of an electrophilic aromatic substitution reaction. However, the presence of the imino group adjacent to the aromatic ring strongly stabilizes the corresponding intermediate, being the reaction product when the ortho positions are occupied by t-butyl substituents. This domino reaction shows a great similitude with the Brønsted acid catalyzed Povarov reaction. Although N-phenyl iminoborane can experience a formal [2+2] cycloaddition reaction with benzaldehyde, its higher activation Gibbs free energy compared to the intramolecular electrophilic attack of the activated carbonyl carbon of benzaldehyde on the ortho position of the N-phenyl substituent, 6.6 kcal·mol−1, prevents the formation of the formal [2+2] cycloadduct. The present MEDT study provides a different vision of the molecular mechanism of these reactions based on the electron density. [ABSTRACT FROM AUTHOR]

In light of the low yields and complex reaction routes of some well-known 5,5-fused and 5,6-fused bicyclic compounds, a series of 5,7-fused bicyclic imidazole-diazepine compounds were developed with high yields by only two efficient steps. Significantly, the seven-membered heterocyclic ring has a stable energetic skeleton with multiple modifiable sites. However, the 5,7-fused bicyclic energetic compounds were rarely reported in the area of energetic materials. Three neutral compounds 1, 2 and 4 were synthesized in this work. To improve the detonation performances of the 5,7-fused neutral compounds, corresponding perchlorate 1a and 2a were further developed. The physicochemical and energetic performances of all newly developed compounds were experimentally determined. All newly prepared energetic compounds exhibit high decomposition temperatures (Td: 243.8-336 °C) and low mechanical sensitivities (IS: >15 J, FS: >280 N). Among them, the velocities performances of 1a (Dv = 7651 m/s) and 4 (Dv = 7600 m/s) are comparable to that of typical heat-resistant energetic material HNS (Dv = 7612 m/s). Meanwhile, the high decomposition temperature and low mechanical sensitivities (Td = 336 °C; IS = 32 J; FS > 353 N) of 4 are superior to that of HNS (Td = 318 °C; IS = 5 J; FS = 250 N). Hence, the 5,7-fused bicyclic compounds with high thermostability, low sensitivities and adjustable detonation performance have a clear tendency to open up a new space for the development of heat-resistant energetic materials. [ABSTRACT FROM AUTHOR]

By using tetrazole as the parent structural unit, five new groups of bicyclic tetrazolium-containing compounds (A--E) were designed by introducing a variety of high-energy and bridging groups. The electronic properties and detonation performances of the 35 designed compounds were calculated and analyzed using the density functional theory method at B3LYP/6-311G (d, p) level, and their detonation parameters were compared with those of HMX and other explosives. The results show that the densities of the five kinds of designed compounds are 1.555 9-2. 051 0g/cm³, the heat of formation are 490. 79-1 607. 39kJ/mol, the detonation velocities are 7 590-10 110m/s, and the detonation pressures are 23.34-48.44GPa. When the substituent groups are nitro, nitroamino and trinitro-methyl, the bridging groups are --N(NO2)--CH2--N(NO2)--, --N=N(O)-- and --N=N--, the densities of these compounds are 1. 90-2. 051 0g/cm³, the detonation velocities are 9 000-10 110m/s, the heat of formation(HOFs) are 916--1607kJ/mol, and the energy gap values are 1.45-5.62eV, indicating that they are potential energetic compound candidates with high energy density and excellent performance. [ABSTRACT FROM AUTHOR]

Synthesis of bicyclic scaffolds has attracted tremendous attention because they are playing an important role as saturated bioisosteres of benzenoids in modern drug discovery. Here, we report a BF3‐catalyzed [2π+2σ] cycloaddition of aldehydes with bicyclo[1.1.0]butanes (BCBs) to access polysubstituted 2‐oxabicyclo[2.1.1]hexanes. A new kind of BCB containing an acyl pyrazole group was invented, which not only significantly facilitates the reactions, but can also serve as a handle for diverse downstream transformations. Furthermore, aryl and vinyl epoxides can also be utilized as substrates which undergo cycloaddition with BCBs after in situ rearrangement to aldehydes. We anticipate that our results will promote access to challenging sp3‐rich bicyclic frameworks and the exploration of BCB‐based cycloaddition chemistry. [ABSTRACT FROM AUTHOR]

Design, synthesis and application of benzene bioisosteres have attracted a lot of attention in the past 20 years. Recently, bicyclo[2.1.1]hexanes have emerged as highly attractive bioisosteres for ortho‐ and meta‐substituted benzenes. Herein we report a mild, scalable and transition‐metal‐free protocol for the construction of highly substituted bicyclo[2.1.1]hexan‐2‐ones through Lewis acid catalyzed (3+2)‐cycloaddition of bicyclo[1.1.0]‐butane ketones with disubstituted ketenes. The reaction shows high functional group tolerance as documented by the successful preparation of various 3‐alkyl‐3‐aryl as well as 3,3‐bisalkyl bicyclo[2.1.1]hexan‐2‐ones (26 examples, up to 89 % yield). Postfunctionalization of the exocyclic ketone moiety is also demonstrated. [ABSTRACT FROM AUTHOR]

Aromatic hydrocarbons represent a large fraction of anthropogenic volatile organic compounds and significantly contribute to tropospheric ozone and secondary organic aerosol (SOA) formation. Toluene photooxidation experiments were carried out in an oxidation flow reactor (OFR). We identified and quantified the gaseous and particulate reaction products at 280, 285 and 295 K using a proton-transfer reaction time-of-flight mass spectrometer (PTR-ToF-MS) coupled to a CHemical Analysis of aeRosol ONline (CHARON) inlet. The reaction products accounted for both ring-retaining compounds such as cresols, benzaldehyde, nitrophenols, nitrotoluene, bicyclic intermediate compounds, as well as ring-scission products such as dicarbonyls, cyclic anhydrides, small aldehydes and acids. The chemical system exhibited a volatility distribution mostly in the semi-volatile (SVOCs – semi-volatile organic compounds) regime. The saturation concentration (Ci*) values of the identified compounds were mapped onto the two-dimensional volatility basis set (2D-VBS). Temperature decrease caused a shift of Ci* towards lower values while there was no clear relationship between Ci* and oxidation state. The CHARON PTR-ToF-MS instrument identified and quantified approximately 70–80 % of the total organic mass measured by an aerosol mass spectrometer (AMS). The experiments were reproduced by simulating SOA formation with the SSH-aerosol box model. A semi-detailed mechanism for toluene gaseous oxidation was developed. It is based on the MCM and GECKO-A deterministic mechanisms modified following the literature in particular to update cresols and ring-scission chemistry. The new mechanism improved secondary species representation with an increment of the major identified species (+35 % in number). Light compounds formation (i.e. m/z < 100) is enhanced and accumulation of heavy compounds (i.e. m/z ≥ 100) is reduced, especially in the gas phase. Additional tests on (i) partitioning processes such as condensation into aqueous phase, (ii) interactions of organic compounds between themselves and with inorganics and (iii) wall losses were also performed. When all these processes were taken into account the simulated SOA mass concentration showed a much better agreement with the experimental results. Finally, an irreversible partitioning pathway for methylglyoxal was introduced and considerably improved the model results, opening a way to further developments of partitioning in models. Our results underline that the volatility itself is not sufficient to explain the partitioning between gas and particle phase: the organic and the aqueous phases need to be taken into account as well as interactions between compounds in the particle phase. [ABSTRACT FROM AUTHOR]

The study diagnosed chemistry teacher trainees’ difficulties in naming and writing structures of spiro and bicyclic compounds. The case study design was conducted in a constructivist environment to enhance chemistry teacher trainees’ ability to construct, represent, and interpret the structural formulae of spiro and bicyclic compounds. Purposive sampling technique was employed to select 126 1st-year chemistry teacher trainees from University of Education, Winneba for the study. The results revealed that chemistry teacher trainees had difficulties in naming and writing structural formulae of spiro and bicyclic compounds. However, through the effective use of molecular model kits in teaching naming and writing structures of spiro and bicyclic compounds, these chemistry teacher trainees became conscious of IUPAC rules for naming and writing spiro and other cyclic compounds. A t-test conducted indicated that a statistical significance difference existed between students’ performance before the implementation of the intervention and after the intervention. It is recommended that chemistry teachers should adopt the use of molecular model kits in teaching concepts of organic nomenclature.

3-Azabicyclo[3.1.0]hexanes are common structural components in natural products and bioactive compounds. Traditionally, the metal-mediated cyclopropanation domino reaction of chain enzymes is the most commonly used strategy for the construction of this type of aza[3.1.0]bicycle derivative. In this study, a base-promoted intramolecular addition of alkenes used to deliver conformationally restricted highly substituted aza[3.1.0]bicycles is reported. This reaction was tailor-made for saturated aza[3.1.0] bicycle-containing fused bicyclic compounds that may be applied in the development of concise and divergent total syntheses of bioactive compounds. [ABSTRACT FROM AUTHOR]

Sulfonylated aromatics are commonplace motifs in drugs and agrochemicals. However, methods for the direct synthesis of sulfonylated non‐classical arene bioisosteres, which could improve the physicochemical properties of drug and agrochemical candidates, are limited. Here we report a solution to this challenge: a one‐pot halosulfonylation of [1.1.1]propellane, [3.1.1]propellane and bicyclo[1.1.0]butanes that proceeds under practical, scalable and mild conditions. The sulfonyl halides used in this chemistry feature aryl, heteroaryl and alkyl substituents, and are conveniently generated in situ from readily available sulfinate salts and halogen atom sources. This methodology enables the synthesis of an array of pharmaceutically and agrochemically relevant halogen/sulfonyl‐substituted bioisosteres and cyclobutanes, on up to multidecagram scale. [ABSTRACT FROM AUTHOR]

Chitin, the second most abundant biopolymer in the planet after cellulose, represents a renewable carbon and nitrogen source. A thrilling opportunity for the valorization of chitin is focused on the preparation of biomass-derived N-doped carbonaceous materials. In this contribution, chitin-derived N-doped carbons were successfully prepared and functionalized with palladium metal nanoparticles. The physicochemical properties of these nanocomposites were investigated following a multi-technique strategy and their catalytic activity in reductive amination reactions was explored. In particular, a biomass-derived platform molecule, namely furfural, was upgraded to valuable bi-cyclic compounds under continuous flow conditions. [ABSTRACT FROM AUTHOR]

We represented herein a two-step synthesis of 1-methyl-6 H -indol-6-one which is an N -containing 6/5 fused bicyclic building blocks in Amaryllidaceae alkaloids. The key step featured is a 'one-pot' ozonolysis/reductive amination/cyclization of allylated cyclohexa-1,3-dione to give bicyclic compounds. Moreover, the formal total synthesis of natural product γ-lycorane could be achieved through a photo-promoted cyclization/oxidation cascade reaction from the resulting bicyclic intermediate. [ABSTRACT FROM AUTHOR]

We report the stereocontrolled synthesis of 1,6-diazecanes via a tandem aza-Prins type reaction of N-acyliminium ions with allylsilanes. It involves an aza-Prins type dimerization and cyclization in a single-step operation. This reaction represents the first example of 10-membered N-heterocycle synthesis using an aza-Prins reaction. Also, the interesting formation of an unusual tetracyclic compound through further cyclization of 1,6-diazecane and bicyclic compounds by the intramolecular cyclization of linear allylsilane are described. This tandem aza-Prins protocol provides a new synthetic strategy for the direct synthesis of medium-sized nitrogen heterocycles. [ABSTRACT FROM AUTHOR]

Despite the favorable properties that azetidine rings can engender on drug‐compounds, methods for the diversity‐oriented synthesis of azetidine‐based structures are significantly underdeveloped. Herein, we report the successful realization of a multicomponent [1,2]‐Brook rearrangement/strain‐release‐driven anion relay sequence and its application to the modular synthesis of substituted azetidines. The rapidity of the reaction, as confirmed by in situ infra‐red spectroscopy, leverages the strain‐release ring‐opening of azabicyclo[1.1.0]butane to drive the equilibrium of the Brook rearrangement. The three electrophilic coupling partners, added sequentially to azabicyclo[1.1.0]butyl‐lithium, could be individually varied to access a diverse compound library. The utility of this methodology was demonstrated in a 4‐step synthesis of the EP2 receptor antagonist PF‐04418948. [ABSTRACT FROM AUTHOR]

A number of highly efficient methods for the preparation of novel derivatives of 9-selenabicyclo[3.3.1]nonane in high yields based on selenium dibromide and cis,cis-1,5-cyclooctadiene are reported. The one-pot syntheses of 2,6-diorganyloxy-9-selenabicyclo[3.3.1]nonanes using various O-nucleophiles including alkanols, phenols, benzyl, allyl, and propargyl alcohols were developed. New 2,6-bis(1,2,3-triazol-1-yl)-9-selenabicyclo[3.3.1]nonanes were obtained by the copper-catalyzed 1,3-dipolar cycloaddition of 2,6-diazido-9-selenabicyclo[3.3.1]nonane with unsubstituted gaseous acetylene and propargyl alcohol. The synthesis of 2,6-bis(vinylsulfanyl)-9-selenabicyclo[3.3.1]nonane, based on the generation of corresponding dithiolate anion from bis[amino(iminio)methylsulfanyl]-9-selenabicyclo[3.3.1]nonane dibromide, followed by the nucleophilic addition of the dithiolate anion to unsubstituted acetylene, was developed. The glutathione peroxidase-like activity of the obtained water-soluble products was estimated and compounds with high activity were found. Overall, 2,6-Diazido-9-selenabicyclo[3.3.1]nonane exhibits the highest activity among the obtained compounds. [ABSTRACT FROM AUTHOR]

The norbornene scaffold has arisen as a promising structure in medicinal chemistry due to its possible therapeutic application in cancer treatment. The development of norbornene-based derivatives as potential chemotherapeutic agents is attracting significant attention. Here, we report an unprecedented review on the recent advances of investigations into the antitumoral efficacy of different compounds, including the abovementioned bicyclic scaffold in their structure, in combination with chemotherapeutic agents or forming metal complexes. The impact that structural modifications to these bicyclic compounds have on the antitumoral properties and the mechanisms by which these norbornene derivatives act are discussed in this review. In addition, the use of norbornene, and its related compounds, encapsulation in nanosystems for its use in cancer therapies is here detailed. [ABSTRACT FROM AUTHOR]

Among gynecological tumors, cervical cancer (CC) has the second‐highest prevalence and mortality rate. α‐Pinene is a bicyclic monoterpenoid compound extracted from pine needles that carried promising anticancer properties. Nevertheless, its effect on CC and the underlying mechanism has not yet been elucidated. Therefore, we investigated the effect of α‐Pinene on apoptosis in CC via in vitro assays of flow cytometry (FCW), terminal deoxynucleotidyl transferase‐mediated nick end labeling (TUNEL) assay, quantitative real‐time polymerase chain reaction (qRT‐PCR), and Western blot. Following that, we detected the proapoptotic function of α‐Pinene on HeLa cells in vivo by TUNEL assay and immunofluorescence staining. Our results displayed that the α‐Pinene inhibited the growth of HeLa cells and stalled the cells in the G0/G1 phase. Interestingly, we also detected that α‐Pinene induced HeLa cells to apoptosis. The results investigated that α‐Pinene induced HeLa cells apoptosis along with up‐regulating the expression of Bax, Bid, caspase‐9, caspase‐3, miR‐34a‐5p, and down‐regulating the expression of Bcl‐2 in vitro. At the same time, the expression levels of target genes in vivo were consistent with those in vitro. Our experiment proved that α‐Pinene promoted apoptosis, which will be used to hopefully maximize the therapeutic strategies in clinical studies in CC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Neuroprotective effects of 26 chiral bicyclic γ-butyrolactones were evaluated. • Bd showed good neuroprotective properties against oxidative stress. • The neuroprotective effects of bd were exerted by inhibiting apoptosis. Oxidative stress plays a pivotal role in various neurological disorders, encompassing both neurodegenerative diseases such as Alzheimer's and Parkinson's, and mood disorders like depression. The balance between the generation of reactive oxygen species (ROS) and the cell's antioxidant defenses, when disrupted, can lead to neuronal damage and neurologic dysfunction. In this study, we focused on the pathogenic role of oxidative stress in various neurologic disease models in vitro and investigated the neuroprotective capabilities of some novel bicyclic γ-butyrolactone compounds, with particular emphasis on the compound designated as 'bd'. Our investigation leveraged the HT22 and SH-SY5Y cells to model oxidative stress induced by H 2 O 2 or corticosterone (CORT), common triggers of neuronal damage in neurodegenerative and mood disorders. We discovered that compound bd robustly reduced ROS production and suppressed neuronal apoptosis, suggesting its potential in treating a wider array of neurological conditions influenced by oxidative stress. In conclusion, our research underscores the importance of addressing oxidative stress in the context of diverse neurological disorders. The identification of compound bd as a neuroprotective agent with potential efficacy against ROS-induced apoptosis in neural cells opens new horizons for therapeutic development, offering hope for patients suffering from neurodegenerative diseases, depression, and other stress-related neurological conditions. [ABSTRACT FROM AUTHOR]

A method for the synthesis of aminomethyl-substituted five-membered sultams has been developed. The aminomethyl sultams were synthesized from the corresponding iodomethyl derivatives by nucleophilic substitution of the iodine atom with sodium azide followed by reduction on Pd/C. This method was further expanded to side-chain-substituted sultams, starting from amino acid esters, to obtain aminomethyl-containing bicycles. The simple practical procedure and available starting amino acid esters, including chiral examples, make various bicyclic sultams readily available. [ABSTRACT FROM AUTHOR]

Functionalized 4,4‐difluorospiro[2.2]pentan‐1‐yl derivatives are proposed as promising building blocks for synthetic and medicinal chemistry. Scalable, efficient, and diastereoselective approach to their preparation via the difluorocyclopropanation of (2‐methylenecyclopropyl)methanol is developed. Stability of the title scaffolds towards common reaction conditions is confirmed by a series of typical functional group transformations. Physicochemical characteristics (pKa, logP, and aqueous solubility) and structural features of the key 4,4‐difluorospiro[2.2]pentan‐2‐yl derivatives are established and compared with those of non‐fluorinated analog, 2,2‐difluorinated isomer, as well as monocyclic gem‐difluorinated counterparts. [ABSTRACT FROM AUTHOR]

Transannular reactions have shown a remarkable performance for the construction of polycyclic scaffolds from medium- or large-sized cyclic molecules in an unconventional manner. Recent examples of transannular reactions reported from 2011 have been reviewed, emphasizing the excellent performance of this approach when accessing the target compounds. This review also highlights how this methodology provides an alternative approach to other commonly used strategies for the construction of cyclic entities such as cyclization or cycloaddition reactions. 1 Introduction 2 Transannular Cycloadditions and Electrocyclizations 3 Transannular Conjugate Additions 4 Transannular 1,2-Addition to Ketones, Imines, Esters, and Amides 5 Transannular Reactions via Electrophilic Activation of Olefins 6 Transannular Ring-Opening of Epoxides 7 Transannular Alkylations of Enolates and Related Species 8 Miscellaneous Transannular Reactions 9 Concluding Remarks [ABSTRACT FROM AUTHOR]

The study diagnosed chemistry teacher trainees' difficulties in naming and writing structures of spiro and bicyclic compounds. The case study design was conducted in a constructivist environment to enhance chemistry teacher trainees' ability to construct, represent, and interpret the structural formulae of spiro and bicyclic compounds. Purposive sampling technique was employed to select 126 1st-year chemistry teacher trainees from University of Education, Winneba for the study. The results revealed that chemistry teacher trainees had difficulties in naming and writing structural formulae of spiro and bicyclic compounds. However, through the effective use of molecular model kits in teaching naming and writing structures of spiro and bicyclic compounds, these chemistry teacher trainees became conscious of IUPAC rules for naming and writing spiro and other cyclic compounds. A t-test conducted indicated that a statistical significance difference existed between students' performance before the implementation of the intervention and after the intervention. It is recommended that chemistry teachers should adopt the use of molecular model kits in teaching concepts of organic nomenclature. [ABSTRACT FROM AUTHOR]

Donor‐acceptor cyclopropanes or cyclobutanes are dipolar reagents, which are widely used in the synthesis of complex organic (hetero)cycles in ring expansion reactions. Applying this concept to boron containing heterocycles, the four‐membered borete cyclo‐iPr2N‐BC10H6 reacted with the carbon donor ligands 2,6‐xylylisonitrile and the carbene IMes :C(NMesCH)2 with ring expansion and ring fusion, respectively. In particular, the tetracyclic structure formed with IMes displays zwitterionic character and absorption in the visible region. In contrast to the carbene IMes, the heavier carbenoids :Si(NDippCH)2 and :Ga(AmIm) with a two‐coordinate donor atom afford spiro‐type bicyclic compounds, which display four‐coordinate geometry at silicon or gallium. (TD‐)DFT calculations provide deeper insight into the mechanism of formation and the absorption properties of these new compounds. [ABSTRACT FROM AUTHOR]