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We report facile and versatile procedures for the synthesis of exo - and endo -isomeric spirocyclic hybrids of pharmacophoric (1 R ,5 S)-8-azabicyclo[3.2.1]octane (nortropane) and 1,3-oxazinan-2-one fragments. Our approach consists of the hydrocyanation of endo - and exo -isomeric N -Cbz-protected nortropane-3-spiroepoxides, the reduction of hydroxy nitriles into amino alcohols, the synthesis of N -alkylated amino alcohols via reductive amination, the spirocyclization of the amino alcohols, N -alkylation of the unsubstituted 1,3-oxazinan-2-one fragment in the spiro compounds, and removal of the Cbz protecting groups. [ABSTRACT FROM AUTHOR]

The unique reactivity and beneficial features of the 5-aminotetrazole synthon (1 H -tetrazol-5-amine) have made it a versatile and effective building block in the synthesis of heterocyclic compounds. In addition, several drugs containing this scaffold with a wide array of biological properties have been already introduced. Heterocyclic structures are the backbone of many biologically active and industrially important compounds. 5-Aminotetrazole is one of the favored synthons used in the preparation of heterocycle-bearing compounds, especially in multicomponent synthesis. This review highlights a comprehensive overview of the emerging applications of 5-aminotetrazole as a key component in the synthesis of heterocyclic frameworks through multicomponent reactions, reported between 2017 and July 2023. 1 Introduction 2 5-Aminotetrazole 3 Tetrazolopyrimidine Compounds 4 Spiro Compounds 5 Miscellaneous 6 Conclusion [ABSTRACT FROM AUTHOR]

Here a base‐mediated formal [2+4] annulation of 3‐hydroxyoxindoles with 1,2‐bis(bromomethyl)benzene have been accomplished, affording spirooxindole‐fused oxacycles in good yields. This protocol features great functional group tolerance in mild reaction conditions. Gram‐scale synthesis and further transformation have also been demonstrated. [ABSTRACT FROM AUTHOR]

A chiral shape‐persistent macrocyclic compound (Si‐[3]), designed by the C/Si substitution in the spiro‐atom of spirobifluorene in the cyclic trimer (C‐[3]), has been successfully synthesized in this study. The C/Si substitution made the spiro‐conjugation and energy levels of HOMO and LUMO decrease. Due to the silicon substitution, the macrocyclic compound Si‐[3] was able to be degraded by fluoride ions, but its reaction rate was slower than that of the unsubstituted spirosilabifluorene, showing the chemical stability of Si‐[3]. Furthermore, the chiroptical properties of Si‐[3] with D3‐symmetric macrocyclic structure were investigated, and (P,P,P)‐Si‐[3] showed a high emission quantum yield (Φf=80 %) and moderate dissymmetry factor of circularly polarized luminescence (CPL) (glum,exp=−1.2×10−3). According to the time‐dependent density‐functional theory (TD‐DFT) calculations using polarizable continuum model (PCM), the bright CPL from Si‐[3] was explained by a planarization of one bisilafluorenyl moiety at the excited state, which is responsible for the almost fully‐allowed radiative transition with a short emission lifetime of τf=1.89 ns. [ABSTRACT FROM AUTHOR]

A new method for the intramolecular electrophilic ipso -cyclization of alkynes with triflic anhydride-activated sulfoxides, followed by demethylation with triethylamine in one pot, is described for the synthesis of 3-thiospiro[4.5]-decatrienones in moderate to good yields. This method provides a facile strategy for assembling the sulfur-substituted spirocyclic compounds. [ABSTRACT FROM AUTHOR]

4′-Nitro-2 H -spiro[acenaphthylene-1,2′-pyrrolidine]-2-one derivatives are prepared via [3+2] cycloaddition reactions of azomethine ylides, generated in situ from acenaphthoquinone and primary amines, with β-nitrostyrenes in the presence of (i Pr)2 NEt in methanol. Evidence for the structures of the products was obtained from single-crystal X-ray analysis. The important feature of this diastereoselective synthesis of NH-unprotected spiropyrrolidines is the formation of four contiguous stereogenic centers, one of which is quaternary, with high selectivity. [ABSTRACT FROM AUTHOR]

Noncovalent spatial interaction has become an intriguing and important tool for constructing optoelectronic molecules. In this study, we linearly attached three conjugated units in a multi π‐stacked manner by using just one trident bridge based on indeno[2,1‐b]fluorene. To achieve this structure, we improved the synthetic approach through double C−H activation, significantly simplifying the preparation process. Due to the proximity of the C10, C11, and C12 sites in indeno[2,1‐b]fluorene, we derived two novel donor|acceptor|donor (D|A|D) type molecules, 2DMB and 2DMFB, which exhibited closely packed intramolecular stacking, enabling efficient through‐space charge transfer. This molecular construction is particularly suitable for developing high‐performance thermally activated delayed fluorescence materials. With donor(s) and acceptor(s) constrained and separated within this spatially rigid structure, elevated radiative transition rates, and high photoluminescence quantum yields were achieved. Organic light‐emitting diodes incorporating 2DMB and 2DMFB demonstrated superior efficiency, achieving maximum external quantum efficiencies of 28.6 % and 16.2 %, respectively. [ABSTRACT FROM AUTHOR]

Nucleophilic ring-opening of 1,6,10,14-tetraoxatetraspiro[2.1.25.1.29.1.213.13]hexadecane, a cyclooctane structure spiro-fused with four oxirane fragments, under the action of sodium azide was studied. Depending on the relative configuration of stereocenters in the starting compound, the reaction proceeded as an intramolecular transannular cyclization with the formation of a 9-oxabicyclo[3.3.1]nonane skeleton or as an independent nucleophilic opening of the oxirane rings, leading to tetraazido tetraols of the cyclooctane series. [ABSTRACT FROM AUTHOR]

Spirocyclic scaffolds have received increasing interest because of their wide use in medicinal chemistry and the need for designing new effective drugs on their basis. Electroorganic synthesis is an environmentally friendly method for the preparation of organic compounds because hazardous and toxic redox reagents are replaced by electric current and the overall energy costs are reduced. Modern methods for the electrosynthesis of spiro compounds and the prospects of their development are analyzed. The review summarizes the data on the types of electrochemical and electrocatalytic methods. The potential practical applications of these methods for the preparation of individual classes of spirocycles are discussed. [ABSTRACT FROM AUTHOR]

The reactivity of an isolable 2‐germapropadiene with acids, ketones, and amines was investigated. The reactions of 2‐germapropagiene 1 with hydrogen chloride and acetic acid afforded the corresponding dichlorogermane (2) and diacetoxygermane (3), respectively, indicating that the central germanium atom of 1 is electrophilic. The reaction of 1 with benzaldehyde proceeds via a formal [2+2] cycloaddition to afford the corresponding spiro compound (4). Moreover, 1 reacts smoothly with acetone to furnish germane 5, which contains a six‐membered ring involving two acetone molecules. Furthermore, 1 undergoes N−H bond insertion with methylamine or aniline to afford diamino germanes 7 and 8, respectively. The reaction of 1 with urea selectively afforded the corresponding N−H−insertion product (8). [ABSTRACT FROM AUTHOR]

This article explores the synthesis of medium-sized lactones, which are important structural components in natural products and pharmaceuticals. The authors provide examples of specific lactones and their biological activities. They then discuss their own research on synthesizing benzannulated lactams and lactones using a specific starting material and different reaction conditions. The article includes a table summarizing their experimental results, demonstrating the formation of various lactones. The authors conclude by discussing the implications and potential applications of their findings. The study was supported by Evonik Industries, and the authors express gratitude to individuals who assisted in the laboratory. [Extracted from the article]

The previously unknown cyclopropane spiro-fused with isoxazol-5-one ((1RS,3SR)-1-(4-methylbenzyl)-7-phenyl-5-oxa-6-azaspiro[2.4]hept-6-en-4-one) was synthesized from benzylideneisoxazol-5-one in 34% yield via double methylene transfer from diazomethane. The structure of the compound was established based on 1H, 13C, and 2D NMR spectroscopy and high-resolution mass spectrometry, and confirmed by X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Within this work we have investigated spiro‐based tetrathiafulvalenes (TTFs) obtained as mixtures of stereoisomers from racemic spiro[5.5]undeca‐1,8‐dien‐3‐one. Compared to previously described spiro‐TTFs, enantiomeric and diastereoisomeric forms have been here separated by chiral HPLC and fully characterized both experimentally and theoretically. The two types of spiro‐based chiral derivatives contain either one (2) or three (1) chiral centres out of each one is spiro‐type. Experimental CD, supported by TD‐DFT calculations, shows differences in the optical activity between the 1 and 2 and their intermediates. The low optical activity of 2 and 3 (spiro alone chirality) was attributed to the presence of two conformers in the solution (ax and eq) of opposite Cotton effect whereas in the case of 1 and 5 (spiro and stereogenic centres) the spiro chirality seems to be responsible of the Cotton effect in the high energy region whereas the R and S chirality in the low energy region. Racemic and enantiopure forms have been successfully used for the synthesis of charge transfer complexes with tetracyanoquinodimethane (TCNQ) based acceptors. [ABSTRACT FROM AUTHOR]

The derivatives of 1,2,4- triazole have attracted great attention among medicinal chemists due to their wide range of biological activity, good pharmacodynamic and pharmacokinetic profiles, and low toxicity, that necessitates the development of various synthesis methods and a comprehensive study of their reaction mechanisms. A detailed investigation of possible pathways for formation of new spiro-condensed [1,2,4]triazolo[1,5-c]quinazolines, that combine two structural domains with different biological properties, was performed by computational study at the SMD/B3lyp/6-31+G(d) theory level. The mechanism of interaction between [2-(3-hetaryl-1,2,4-triazol-5-yl)phenyl]amine and cyclohexanone in methanol involves three main processes: formation of carbinolamine by addition of an amine to double bond C=O, elimination of a water molecule, and intramolecular cyclization leading to formation of spiro compounds. Results show increase in reactivity of reactants during acid-catalyzed reaction compared to uncatalyzed one. The nature of the heterocyclic substituent on the triazole ring has little effect on the reaction energy, while the mechanism is unchanged. [ABSTRACT FROM AUTHOR]

Elaborated molecular architectures, specifically those bearing one or more carbon stereocenters, stand as an important class of carbocyclic and heterocyclic frameworks because they are frequently occurring core structures in numerous natural products and biologically active pharmaceutical molecules. Over the past few decades, the development of versatile synthetic approaches via cascade cyclization reactions of 1,6‐enynes for the construction of a series of fused and spiro compounds has been the focus of a great deal of research initiatives. These synthesis strategies are peculiarly fascinating in the context of the assembly of a wide array of pharmaceutical molecules, natural products, agrochemicals, and functional materials. In this review, recent developments in the transformations of 1,6‐enynes with diverse coupling reagents are summarized since 2018, which could be divided into five categories: 1) Introduction; 2) Transition metal catalyzed cyclization of 1,6‐enynes; 3) Metal‐free cyclization of 1,6‐enynes; 4) Visible‐light‐induced cyclization of 1,6‐enynes; 5) Electrocatalytic cyclization of 1,6‐enynes. [ABSTRACT FROM AUTHOR]

Two previously described Brønsted acidic ionic liquids, 3,3′-(1,6-hexanediyl)bis(1-methyl)-1H-imidazolium hydrogen sulfate (Cat1) and 1,1′-(1,6-hexanediyl)bis(pyridinium) hydrogen sulfate (Cat2), were used as catalysts for the preparation of spiro[furan-2,3′-indoline]-3-carboxylate derivatives via a three-component reaction of anilines, isatins (N-alkyl-indoline-2,3-diones), and diethyl acetylenedicarboxylate, in high yields. The use of ultrasonic (US) irradiation led to the targeted products (1a–15a) in high yields ranging from 80% to 98%. Under the same conditions, the use of sulfuric acid and acetic acid as a Brønstedt catalyst did not yield the desired benchmark product 1a. [ABSTRACT FROM AUTHOR]

Trifluoro‐ and trichloroacetamides serving as pronucleophiles undergo enantioselective Lewis base catalyzed N‐allylation with Morita‐Baylis‐Hillman carbonates to produce enantioenriched β‐amino acid derivatives. The reactions proceed as a kinetic resolution to give the allylation products and the remaining carbonates in good yields and high enantioselectivity. The obtained products are amenable to diastereoselective derivatization to produce a library of spiro‐isoxazoline lactams. [ABSTRACT FROM AUTHOR]

The condensation of 3-benzyl-2-sulfanylidene-2,3-dihydro-1H-spiro[benzo[h]quinazoline-5,1′-cyclo-heptan]-4(6H)-one with 5,5-dialkyl-2-(chloromethyl)benzo[h]quinazolines gave bis-benzo[h]quinazoline compounds in which the spiro[benzo[h]quinazoline-5,1′-cycloheptane] fragment is linked through the 2-position to another benzo[h]quinazoline moiety via a SCH2 spacer. 3-Benzyl-2-sulfanylidene-2,3-dihydro-1H-spiro-[benzo[h]quinazoline-5,1′-cycloheptan]-4(6H)-one reacted under similar conditions with methylene iodide to produce 2,2′-[methylenebis(sulfanediyl)]bis{3-benzyl-3H-spiro[benzo[h]quinazoline-5,1′-cycloheptan]-4(6H)-one}. The initial benzo[h]quinazoline was converted to 2-hydrazinyl derivative which underwent elimination of the hydrazine moiety by the action of alkali with the formation of 3-benzyl-3H-spiro[benzo[h]quinazoline-5,1′-cycloheptan]-4(6H)-one. The 2-hydrazinyl derivative was used to obtain the corresponding phenylhydrazone, thiosemicarbazide, and 4-benzyl-4H-spiro[benzo[h][1,2,4]triazolo[4,3-a]quinazoline-6,1′-cycloheptanone]-5(7H)-one. The alkylation of 4-benzyl-1-sulfanyl-4H-spiro[benzo[h][1,2,4]triazolo[4,3-a]quinazoline-6,1′-cycloheptan]-5(7H)-one with alkyl halides afforded the corresponding 1-alkylsulfanyl derivatives. The synthe-sized compounds were tested for antibacterial activity. [ABSTRACT FROM AUTHOR]

The enhancement of 3D character in chemical scaffolds has become an unavoidable space and a key component for diverse applications. Herein, we report a simple phenol-derived catalyst with synergistic involvement of electronic and electrostatic sites to access spirocyclic carbonates from spiroepoxy oxindoles and carbon dioxide. The metal-free and co-catalyst free catalytic system demonstrates excellent activity in synthesizing diverse spirocyclic carbonates with good conversions (up to 99%) under ambient reaction conditions. Volumetric and NMR investigations enabled the synergistic role of the key chemical functionalities in the catalyst and elucidated the probable reaction mechanism. The calculated values of different green metrics revealed the suitability and practical applicability of the catalytic system. [ABSTRACT FROM AUTHOR]

A domino SNAr‐ihDA/rDA reaction was developed from rarely exploited 3‐fluoro‐1,2,4‐triazines with bifunctional alkyne tethered nucleophiles to construct various fused non‐aromatic/heteroaromatic bicycles in yields ranging from 56 to 99%, notably within the family of valuable spirooxindole derivatives. In this study, the challenging enantioselective phase‐transfer catalyzed arylation of a sulfonyl‐triazine was also demonstrated with up to 66% ee. In both racemic and asymmetric processes, the nature of the leaving group at C3 was key to successfully achieve these sequences. [ABSTRACT FROM AUTHOR]

Isatin, also known as indoline‐2,3‐dione, is a fused, N‐heterocyclic aromatic compound first isolated and purified in 1841. Since then, isatin and its derivatives emerged as a hot research topic for the scientific community. The number of research publications on isatin justifies their popularity. Researchers explored isatins and their derivatives as potential candidates in multidisciplinary research areas, including medicinal chemistry, synthetic organic chemistry, and polymer science. Synthetic chemists' perspective of tailoring isatin and its family members led to more efficient synthesis strategies in which ring‐opening reactions of isatins were particularly significant due to the product's importance. Our investigation aims to group the different types of cascade ring expansion reactions of isatin to synthesise fused heterocyclic compounds such as derivatives of quinolines, quinazolinones, acridines, acridones, and few spiro heterocyclic compounds, all of which highlight an inevitable role in the field of medicinal chemistry. [ABSTRACT FROM AUTHOR]

Herein, we report the unusual skeletal rearrangement of spiro[4.5]decadienone to benzoxepane. In particular, Lewis acid‐promoted epoxide‐opening ipso‐cyclization of aryl epoxides afforded spiro[4.5]decadienone intermediates. Subsequent thermal activation assembled a benzoxepane core via rearomative molecular reorganization. The sequence was high‐yielding and highly diastereoselective but sensitive to the aromatic substitution pattern and the epoxide side chain. Mechanistic studies suggested that the rearrangement proceeded via an uncommon intramolecular enolate attack onto the electrophilic O of p‐quinone oxonium zwitterion. DFT calculations helped rationalize the product distribution and the origin of diastereoselectivity. Initial investigation into the application of this chemical transformation is also presented. [ABSTRACT FROM AUTHOR]

Spiro compounds with unique structural and electronic properties are beneficial for thermally activated delayed fluorescence (TADF) emitters. Herein, a series of spiro boron‐nitrogen (B‐N) compounds are reported with donor–acceptor (D‐A) interaction through homoconjugation. Three phenyl acridine‐containing spiro B‐N compounds exhibit highly efficient photoluminescence (PL) in degassed toluene and solid‐state with obvious TADF character. The separation of HOMO and LUMO for these compounds is confirmed by theoretical calculations, as is the small ΔEST of phenyl acridine‐containing compounds. These three compounds are used as emitting layers in solution‐processed organic light‐emitting diodes (OLEDs), resulting in deep‐blue to green emission colors with different acceptor moieties. Impressively, an excellent external quantum efficiency (EQE) of 22.1% is recorded for the TPA‐s‐FMesBF‐based OLED device, which is comparable with the highest value from solution‐processed OLEDs based on spiro D‐A emitting materials. This work presents a facile synthetic route to novel B, N‐substituted spiro compounds, as well as the structure‐property relationship of spiro D‐A compounds for highly efficient TADF emitters. [ABSTRACT FROM AUTHOR]

In this research, 2-amino-4,7-dihydro-5H-spiro[benzo[b]thiophene-6,2'- [1,3]dioxolane]-3-carbonitrile (ST) was synthesized using the Gewald method, starting with 1,4-dioxaspiro[4,5]decan-8-one ketone. The structures of compounds were characterized through FT-IR, 1H-NMR, and 13C-NMR spectra. The antimicrobial properties of the compounds were examined by the disk diffusion process. The compounds (N1-3) did not exhibit effectiveness against the E. Coli (ATCC) and S. Aureus (ATCC) bacteria. The molecular electrostatic potential surface (MEP) of all compounds was calculated via DFT calculations based on the optimized geometries at the B3LYP/6-31G (d,p) level of theory. Negative potential regions were located over the oxygen and nitrogen atoms, whereas positive potential regions were identified over the oxygen and sulfur atoms. Conceptually, computations of the molecular structures of the compounds were carried out using molecular modeling software, specifically GaussView 5.0 and the GAUSSIAN 09 package programs. Additionally, computations were performed for the HOMO and LUMO molecular orbitals of isolated molecules in the gas phase. Molecular electrostatic potential (MEP) surfaces were used to visualize potential interactions between receptors and ligands over the steady-state geometries of the molecules and to highlight the electrophilic and nucleophilic regions of the molecules. [ABSTRACT FROM AUTHOR]

The previously unknown cyclopropane spiro-fused with isoxazol-5-one ((1RS,3SR)-1-(4-methylbenzyl)-7-phenyl-5-oxa-6-azaspiro[2.4]hept-6-en-4-one) was synthesized from benzylideneisoxazol-5-one in 34% yield via double methylene transfer from diazomethane. The structure of the compound was established based on 1H, 13C, and 2D NMR spectroscopy and high-resolution mass spectrometry, and confirmed by X-ray diffraction analysis.

The regioselective transformation of alkynes represents a highly efficient bond-forming strategy in organic synthesis. However, the enantiocontrol in the conversion of alkynes remains challenging, especially for the metal-free approach. Herein, we describe a chiral Brønsted acid-catalyzed enantioselective spirocyclization of alkynyl thioethers via dearomatization of phenols. This metal-free protocol leads to the green and atom-economical preparation of chiral spiro[4.5]decan-6-ones in good to excellent yields with high enantioselectivities. Importantly, this protocol represents the first metal-free example of the asymmetric transformation of alkynyl thioethers. [ABSTRACT FROM AUTHOR]

Cyclic [3]spirobifluorenylene with bulky alkyl groups at the ends (1) was designed and synthesized to investigate the electron transfer phenomena in a π‐conjugated system including orthogonal π‐conjugated chains. The three bifluorenyl units in 1 are conjugated to each other via spiro‐conjugation, resulting in the splitting of the HOMO levels to a small extent. Therefore, the SOMO‐HOMO gap of the radical cation species is small, which is considered to allow the facile intramolecular electron transfer. The electronic properties of 1 and its partial structures were characterized by absorption and fluorescence measurements and electrochemical analysis. From the electrochemical oxidation, the interchain Coulombic repulsion was observed. In the TD‐DFT calculations for the radical cation species of 1, the geometry‐featured interchain electronic transitions were visualized by NTO calculations. The radical cation species of 1 generated by chemical oxidation with SbCl5 exhibited a broadened and lower‐energy NIR absorption band exceeding 2000 nm. Considering the results of the TD‐DFT calculations, the NIR band of the radical cation of 1 was attributed to the intramolecular electron transfer processes among the bifluorenyl units in the macrocycle. ESR experiments also indicated the delocalization of a spin of 1⋅+ in the whole molecule via hole hopping in the ESR time scale at room temperature. This work demonstrates the usefulness of spiro‐conjugation as a bridging unit in molecular wires to facilitate smooth electron transfer. [ABSTRACT FROM AUTHOR]

A series of new spiro heterocyclic compounds having carbazole and pyrrolidine units were successfully synthesized through a one‐pot, three component, 1,3‐dipolar cycloaddition reaction in good yields with high diastereoselectivity. Simple reaction, easily accessible chemicals, high yield and diastereoselective formation of monospiropyrrolidine and monospiropyrrolizidine carbazole derivatives in one step are some advantages of this method. The structure of the obtained products was characterized by using spectroscopic techniques. [ABSTRACT FROM AUTHOR]

The forthcoming generation of materials, including artificial muscles, recyclable and healable systems, photochromic heterogeneous catalysts, or tailorable supercapacitors, relies on the fundamental concept of rapid switching between two or more discrete forms in the solid state. Herein, we report a breakthrough in the "speed limit" of photochromic molecules on the example of sterically-demanding spiropyran derivatives through their integration within solvent-free confined space, allowing for engineering of the photoresponsive moiety environment and tailoring their photoisomerization rates. The presented conceptual approach realized through construction of the spiropyran environment results in ~1000 times switching enhancement even in the solid state compared to its behavior in solution, setting a record in the field of photochromic compounds. Moreover, integration of two distinct photochromic moieties in the same framework provided access to a dynamic range of rates as well as complementary switching in the material's optical profile, uncovering a previously inaccessible pathway for interstate rapid photoisomerization. Rapid switching between discrete states in the solid state is a cornerstone for the technological development of devices based on stimuli-responsive materials. Here authors break the speed limit of common classes of photochromic molecules through tailoring framework environments. [ABSTRACT FROM AUTHOR]

The reactions of isatins, 3-amino-1-pheyl-1H-pyrazol-5(4H)-one, and monocyclic ketones, have been developed for preparation of spiro[indoline-3,4'-pyrazolo[3,4-b]quinoline]-2,3'(6'H)-dione, spiro[cyclohepta[b]pyrazolo[4,3-e]pyridine-4,3'-indoline]-2′,3-dione, spiro[cycloocta[b]pyrazolo[4,3-e]pyridine-4,3'-indoline]-2′,3(6H)-dione, and spiro[cyclo dodeca[b]pyrazolo[4,3-e]pyridine-4,3'-indoline]-2′,3(6H)-dione derivatives in aqueous and acetic acid mixed medium. Studies have shown that water was an excellent medium for this reaction. The significant features of this method are wide substrate scope, high yields, operational simplicity, and minimal environment impact. [ABSTRACT FROM AUTHOR]

Herein, an efficient approach to synthesize various hexahydro‐1H‐xanthene‐1,8‐dione or dibenzo xanthene containing bioactive spirooxindole derivatives is reported by using FeCl3 ⋅ 6H2O mediated spiro coupling of 1,3‐diketone or naphthalene‐1‐ol with peroxyoxindole. This new approach proceeds via a sequential oxidative cleavage of the C−C bond of peroxyoxindoles to generate the isatin intermediate and further reaction with two molecules of cyclic‐1,3 diketones through a series of reactions such as Knoevenagel condensation, Michael addition, and dehydration in one‐pot conditions. Furthermore, this sequential reaction of peroxyoxindole with malononitrile afforded 2‐(2‐oxoindolin‐3‐ylidene)malononitriles in very good yields in the presence of the most abundant Fe‐catalyst. A plausible mechanistic pathway in this transformation has been supported with experimental evidence and control experiments. [ABSTRACT FROM AUTHOR]

The article discusses the Hauser-Kraus (H-K) annulation, a reaction used to synthesize natural products and aromatic compounds. It is an environmentally friendly and cost-effective alternative to other methods of benzannulation. The H-K annulation has been successfully used to synthesize quinones, which are found in various natural products and drugs. The article provides examples of the H-K annulation being used in the total synthesis of specific natural products, demonstrating its potential in medicinal chemistry. Various methodologies for the synthesis of different compounds using the H-K annulation reaction are discussed, along with the mechanisms of these reactions. The H-K annulation is a method for synthesizing polycyclic aromatic hydrocarbons and has been used to synthesize various drug molecules and natural products. It does not require transition-metal-mediated conditions and provides products in excellent yields. Recent developments have expanded its potential for synthesizing fused and spiro heterocycles, and further research is expected in the future. [Extracted from the article]

The highly enantioselective organocatalytic synthesis of spirocyclic compounds by Diels‐Alder reactions via trienamine using cyclic 2,5‐dienones as bisvinylogous precursors and different nitroalkenes as dienophiles is described. The use of cinchonidine‐based primary amine as catalyst and benzoic acid as co‐catalyst has allowed the construction of a wide variety of spiro compounds containing three stereogenic centres in good yields and excellent diastereo‐ and enantioselectivities. Additionally, other dienophiles have been evaluated exhibiting different behaviour depending on the electron withdrawing group nature. Subsequent transformations have yielded complex structures with up to five stereocentres. The plausible reaction mechanism has been investigated by computational methods. [ABSTRACT FROM AUTHOR]

Designing deep‐blue fluorophores with a low CIEy is an important request for organic light‐emitting diode (OLED) technology either for display applications or to develop new applications such as light source with antibacterial properties. The challenge of deep‐blue emitting OLEDs mainly relies on the difficulty to reach efficient emitters fulfilling all the characteristics desired to insure a high device performance with suitable CIE coordinates. Herein, we report on the synthesis, the physico‐chemical properties and the application as emissive layer in an OLED of two deep‐blue emitters constructed on the association of Spirofluorene‐N‐PhenylAcridine (SPA‐F) and SpiroBiFluorene (SBF) molecular fragment. Two emitters, 2,2‐SPAF‐SBF and 2,3‐SPAF‐SBF have been constructed following a similar design strategy. The emission wavelength is tuned by the substitution pattern of the SBF backbone (meta or para linkage). Through a structure/properties relationship study, the electrochemical, photophysical and thermal/morphological properties are discussed. When used as emitter in a multi‐layer OLED, 2,2‐SPA‐SBF displays a deep‐blue emission reaching an EQE of ≈1.7% and a Von of 4 V. The electroluminescent spectrum displays a λmax below 400 nm (i.e. 394 nm) and CIE coordinates of (0.182, 0.054). The CIEy coordinate of 0.054 is low and fits the NTSC and EBU standards. [ABSTRACT FROM AUTHOR]

The highly efficient construction of complicated heterocyclic frameworks in an atom‐ and step‐economic manner is still one of the cores of synthetic chemistry. Dearomatization reactions show the unique advantage for the construction of functionalized heterocycles and have attracted widespread attention over the past two decades. The metal‐free approach has proved to be a green and sustainable paradigm for the synthesis of spirocyclic, polycyclic and heterocyclic scaffolds, which are widely present in natural products and bioactive molecules. In this review, the advances in the recent six years (2017–2023) in metal‐free dearomatization reactions are highlighted. Emphasis is placed on developments in the field of organo‐catalyzed dearomatization reactions, oxidative dearomatization reactions, Brønsted acid‐ or base‐promoted dearomatization reactions, photoredox‐catalyzed dearomatization reactions, and electrochemical oxidation dearomatization reactions. [ABSTRACT FROM AUTHOR]

BackgroundAntimicrobial resistance (AMR) in Neisseria gonorrhoeae is an urgent global health threat. Zoliflodacin is a novel antibiotic undergoing clinical trials for the treatment of gonorrhoea. While there are limited data regarding zoliflodacin resistance in N. gonorrhoeae, three amino acid mutations have been associated with increased MICs of zoliflodacin.ObjectivesTo determine the prevalence of three amino acid mutations associated with zoliflodacin resistance within a large, public database of nearly 13 000 N. gonorrhoeae genomes.MethodsPathogenWatch is an online genomic epidemiology platform with a public database of N. gonorrhoeae genomes. That database was used to extract gyrB sequence data and a Basic Local Alignment Search Tool (BLAST) search was performed to identify any of the three amino acid mutations in GyrB that are associated with increased zoliflodacin MICs: D429N, K450N or K450T. As a control for the search methodology, all GyrA sequences were also extracted and S91F mutations were identified and compared with the PathogenWatch database.ResultsIn total, 12 493 N. gonorrhoeae genomes from the PathogenWatch database were included. Among those genomes, none was identified that harboured any of the three mutations associated with increased zoliflodacin MICs. One genome was identified to have a mutation at position 429 in GyrB (D429V).ConclusionsThe findings suggest that the prevalence of the three mutations associated with zoliflodacin resistance in N. gonorrhoeae is very low. However, further research into the mechanisms of zoliflodacin resistance in N. gonorrhoeae is needed. Genomic epidemiology platforms like PathogenWatch can be used to enhance the global surveillance of AMR.

Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation of intron selection has emerged as a route for cancer therapy. Splicing modulators alter the splicing patterns in cells by binding to the U2 snRNP (small nuclear ribonucleoprotein)-a complex chaperoning the selection of branch and 3' splice sites. Here we report crystal structures of the SF3B module of the U2 snRNP in complex with spliceostatin and sudemycin FR901464 analogs, and the cryo-electron microscopy structure of a cross-exon prespliceosome-like complex arrested with spliceostatin A. The structures reveal how modulators inactivate the branch site in a sequence-dependent manner and stall an E-to-A prespliceosome intermediate by covalent coupling to a nucleophilic zinc finger belonging to the SF3B subunit PHF5A. These findings support a mechanism of intron recognition by the U2 snRNP as a toehold-mediated strand invasion and advance an unanticipated drug targeting concept.

Herein, we report a synthetic methodology towards the construction of new cylic alkoxyamines without the prior obtention of their respective nitroxides. These systems are constituted by an indene core connected to a pyrrolidine nucleus through a spiro carbon atom, containing an adjacent α‐hydrogen to the N atom, in order to exhibit the 1‐azaspiro[4.4]nonane frame. Alkoxyamines were synthesised by a free radical‐based spirocyclization, starting from functionalized oxime ethers, involving aryl and neutral alkoxyaminyl radicals in 16–40 % yields. Then, the novel spirocyclic aminoxyl radicals (nitroxides) were detected in ESR spectra, when alkoxyamines were subjected by the thermal homolytic cleavage of their −C−O−N− bond. In general, the temperatures found were in accordance with the increase in the stability of the carbon‐centred radical for the same type of nitroxides. In addition, a spirocyclic alkoxyamine 8 b with α‐hydrogen was employed as initiators/mediators in the styrene bulk homopolymerization, obtaining high conversions and relatively narrow dispersity (Ð~1.5). This suggests that the synthetic methodology used in this research work to obtain α‐hydrogen spirocyclic alkoxyamines would have the potential to be applied in nitroxide‐mediated polymerization (NMP). [ABSTRACT FROM AUTHOR]

Notably, substrates B 1s b and B 1t b bearing a heteroaryl group and a naphthyl group, respectively, also served as suitable reaction partners, participating in the formal (2+1) cycloaddition to provide the benzofuranone-based spirocyclopropanes B 3sa b and B 3ta b , respectively (entries 19 and 20). [15][16][24][32][33] As shown in Scheme 1a, benzofuran-derived oxadienes are widely used as two-atom building blocks in highly diastereoselective (2+3) cycloadditions. Moreover, I ortho i -, I meta i - and I para i -substituted phenyl groups were found to be suitable R SP 1 sp groups for the benzofuran-derived oxadienes B 1 b , affording the target products B 3fa b - B ra b in overall high yields and moderate to good diastereoselectivities (entries 6-18). Keywords: (2+1) cycloaddition; diastereoselectivity; benzofurans; oxadienes; bromomalonates; spiro compounds EN (2+1) cycloaddition diastereoselectivity benzofurans oxadienes bromomalonates spiro compounds 1704 1708 5 08/18/23 20230901 NES 230901 Graph Benzofuran is an important class of oxygen-containing heterocycles that frequently occur as substructures in natural products and synthetic compounds. [Extracted from the article]

Under catalyst-free conditions, an environmentally friendly synthesis of a class of spiropyrane, spiropyranopyrazole, spirobenzofurane, spirobenzofuropyrazole, spirooxadiazolidine, spiro-triazolooxadiazole, spirotriazole, and spirophenanthrene from isatin and different reagents was designed, synthesized, and evaluated for their anticancer activities. Compounds 3, 4, and 9 were formed via a one-pot three-component fusion, and the process of synthesis was interpreted using Knoevenagel condensation, Michael addition, and intramolecular cyclization. The technique of preparation has important benefits such as simple reaction conditions, an easy work-up method, simple separation, and nonchromatographic purification of the products. The 1H, 13C-NMR, and mass spectra of the investigated compounds (2–10) were estimated and matched rather well with the experimental results. The National Cancer Institute (NCI, Bethesda, USA) examined all produced derivatives and found that compound 3 had high anti-cancer cell line activity against non-small cell lung-HCI-H522 (GI% = 93.52%) and melanoma-LOX IMVI (GI%=71.63%). Compounds 7 and 8 also showed inhibitory action, with mean GI% ranging from 9.63% to 35.90%. While Compound 10 demonstrated efficacy against a variety of cell lines representing multiple tumor subpanels, with GI% equal to or more than 40%. Docking experiments with Tyrosine Kinase (PDB ID: 2J5F) were carried out to validate NCI findings. In silico investigations revealed that the majority of the produced spiro compounds satisfied Lipinski's criteria. [ABSTRACT FROM AUTHOR]

Spirocyclic compounds have been extensively studied in recent years. Due to their wide variety of properties, they have a broad range of industrial and pharmacological applications. This has stimulated interest in the synthesis of new derivatives. The aim of the current contribution was to synthesize new multifunctional spirocyclic compounds from tetrahydrobenzoxazolones, which served as versatile starting products for the elaboration of more complex molecules. The spirocyclic compounds were then functionalized in different ways. [ABSTRACT FROM AUTHOR]

A stereo‐, regio‐ and chemoselective synthesis of a series of structurally diverse novel oxobenzothiophene embedded spirooxindolopyrrolidine/pyrrolizidine hybrid heterocycles were achieved in excellent yields by multicomponent 1,3‐dipolar cycloaddition reaction process. The 1,3‐dipole component employed was generated in situ from isatin and N‐methylglycine/L‐proline while the dipolarophile, ethyl 2‐(3‐oxobenzo[b]thiophen‐2(3H)‐ylidene)acetate was prepared from thiophenol in two good yielding steps. The formation of spiroheterocyclic hybrids occurred through the formation of two C=C and one C−N bonds in a single synthetic transformation. The compounds formed consists of three adjacent stereocenters, out of which two are spirocarbons. The synthesized spiro compounds were assayed for their AChE/BChE inhibitory activity and most of the spirocompounds showed promising cholinesterase inhibitory activity. Among them, spiropyrrolidine that substituted with chlorine atom on the oxindole ring displayed significant activity (4.16±0.09 μM) with respect to standard drug, galantamine (2.09±0.11 μM). Molecular modelling simulation was explored for the most potent compound that revealed interesting binding templates to the active site of enzyme. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Benzothiadiazine‐1,1‐dioxide scaffold is bioactive framework with wild utility and applications. Synthesis of benzothiadiazine‐fused isoquinoline derivatives and spiro benzothiadiazine derivatives through transition metal‐catalyzed C—H activation/annulation was reported. 3‐Phenyl‐2H‐benzothiadiazine‐1,1‐dioxide was used as the reaction substrate, and vinylene carbonate and 4‐diazopyrazolone were used as the coupling reagents, respectively. This strategy provides straightforward access to complex N‐heterocycles in a highly efficient and simple manner. [ABSTRACT FROM AUTHOR]

In this study, regio‐ and diastereoselective ring‐opening cyclization of spirocyclopropanes with phosphorus ylides stabilized by electron‐withdrawing groups were developed. The reaction of various cyclohexane‐1,3‐dione‐2‐spirocyclopropanes with phosphorus ylides bearing alkoxycarbonyl groups proceeded smoothly without any additives to provide the corresponding 6,7‐dihydroindan‐4‐ones in 32–87% yields. Cycloheptane‐1,3‐dione‐2‐spirocyclopropanes were also used in this reaction, producing the corresponding products 1,2,3,6,7,8‐hexahydroazulen‐4‐ones in 52–67% yields. The resulting [5.6]‐ and [5.7]‐fused carbocyclic products were readily converted into highly substituted indanes and azulenes, respectively, by oxidation. [ABSTRACT FROM AUTHOR]

Phosphonium‐based compounds gain attention as promising photofunctional materials. As a contribution to the emerging field, we present a series of donor‐acceptor ionic dyes, which were constructed by tailoring phosphonium (A) and extended π‐NR2 (D) fragments to an anthracene framework. The alteration of the π‐spacer of electron‐donating substituents in species with terminal −+PPh2Me groups exhibits a long absorption wavelength up to λabs=527 nm in dichloromethane and shifted the emission to the near‐infrared (NIR) region (λ=805 nm for thienyl aniline donor), although at low quantum yield (Φ<0.01). In turn, the introduction of a P‐heterocyclic acceptor substantially narrowed the optical bandgap and improved the efficiency of fluorescence. In particular, the phospha‐spiro moiety allowed to attain NIR emission (797 nm in dichloromethane) with fluorescence efficiency as high as Φ=0.12. The electron‐accepting property of the phospha‐spiro constituent outperformed that of the monocyclic and terminal phosphonium counterparts, illustrating a promising direction in the design of novel charge‐transfer chromophores. [ABSTRACT FROM AUTHOR]

A new type of neutral mixed‐valence system was synthesized using a facile one‐pot procedure. The spiro‐conjugated framework is additionally "fastened" with a biphenyl bridge, which does not directly participate in spin delocalization but makes the molecule stable and influences the reorganization energy and the energy barrier of the intramolecular electron transfer. The in‐depth experimental and quantum‐chemical study allowed determining the radicals as the Class II Robin‐Day‐mixed‐valence systems. The structure of the radicals was confirmed by the X‐ray data, which are relatively rare for Class II MV molecules. Advanced properties of the radicals, such as an ambipolar redox behavior and panchromatic absorption in the visible and NIR regions, along with their stability, make them of interest for materials science. All radicals demonstrate the SOMO‐HOMO inversion phenomenon, which was supported by the DFT and the experimental study. [ABSTRACT FROM AUTHOR]

Two series of compounds viz. spiro naphthyridine pyrimidine derivatives and N‐(quinolin‐8‐yl)acetamide derivatives which possess the quinoline core moiety were designed and synthesized. The spectral analysis viz. FT‐IR, 1H‐NMR, 13C‐NMR and mass was carried out to establish the structures for the synthesized compounds. In vitro anti‐tubercular activity was done against Mycobacterium tuberculosis H37Rv by following "microplate alamar blue assay (MABA)". The synthesized compounds showed good anti‐tuberculosis (TB) activity with the least minimum inhibitory concentration (MIC) value of 6.25 μg/mL. Computational molecular docking studies were performed out with Mycobacterium tuberculosis enoyl reductase (INHA) (PDB code: 4TZK) using AutoDock to predict the key binding interactions responsible for the activity and the Swiss ADME (absorption, distribution, metabolism, and excretion) tool computed the in silico drug likeliness properties. The synthesized title compounds create a way for the optimization and development of potential drugs against tuberculosis. [ABSTRACT FROM AUTHOR]