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Doping of polycyclic conjugated hydrocarbons (PCHs) with sulfur atoms is becoming more and more important as a means of creating unique functional materials. Recently, thiophene‐containing multiple helicenes have garnered enormous attention due to their intriguing electronic and (chir)optical properties compared with carbohelicenes. However, the efficient synthesis of thiopyran‐containing multiple helicenes and the underlying sulfur doping mechanisms are rather unexplored. Herein, the synthesis and structural analysis of a thiopyran‐containing double [7]helicene 3 are reported. X‐ray crystallographic analysis reveals 3 and its dication with C2‐symmetric propeller‐shape structures and compact interactions in the solid state. 3 exhibits deep‐red to near‐infrared (NIR) fluorescence emission. Tunable aromaticity of the central benzene ring and thiopyran rings is found by chemical oxidation, which is further confirmed by nucleus‐independent chemical shift (NICS), anisotropy of the induced current density (ACID) and harmonic oscillator model of aromaticity (HOMA) analysis. Furthermore, the chiral and photosensitizing characters of 3 are investigated. The excellent deep‐red to NIR fluorescence, circularly polarized luminescence (CPL) and photosensitizing activities suggest that 3 can be used as an outstanding photosensitizer in photodynamic therapy (PDT) and bioimaging, especially paving the way for future CPL‐PDT and CPL‐bio‐probe applications. [ABSTRACT FROM AUTHOR]

A series of 2-thiopyrimidines and thiopyrans were prepared by the reaction of the corresponding α,β-unsaturated ketones with thiourea and Lawesson's reagent, respectively. The synthesized compounds were characterized by spectral analysis and screened for antimicrobial and antioxidant activity. The antimicrobial activity was examined in vitro against gram-positive, gram-negative bacteria and yeast where the results showed that gram-positive bacteria were more susceptible to the tested compounds than gram-negative bacteria and yeast. Among all the compounds evaluated for antioxidant activity, four compounds showed the highest activity (97, 96, 95, and 89%). In silico molecular docking, investigations were undertaken to validate the antibacterial results. The molecular docking results were compatible with the in vitro antibacterial findings. [ABSTRACT FROM AUTHOR]

The alkylation of 4-hydroxythiocoumarins (1a–f) was carried out with various allyl bromides as well as propargyl bromides using K2CO3 (2 equiv.) in anhydrous acetone at room temperature, and the corresponding regioselective S-alkylated products 4a–l and 5a–n were obtained in good yields. Then, the synthesis of a variety of new sulfur heterocycles is accomplished by employing thio-Claisen rearrangement from the corresponding S-allyl ethers (4a–l) and S-propargyl ethers (5a–n) to provide the cyclised products 7a–o and 8a–n in good yields. Interestingly, the S-propargyl ethers of the corresponding 4-hydroxythiocoumarins (1a–f) provided two different products depending on the solvent. Furthermore, various 4-hydroxythiocoumarins provided the cyclised products 10a–f directly upon reaction with 2-methylbut-3-yn-2-ol (9) in the presence of 10 mol% p-TSA as catalyst in nitromethane solvent at 80 °C. DFT calculations were performed to investigate the formation of different products, and the findings have been thoroughly discussed. The results demonstrate several notable attributes, including good to excellent yield, highly regioselective product formation, and high atom economy. [ABSTRACT FROM AUTHOR]

A C–H arylation of thiopyran derivatives with aryl halides has been developed. Under the catalysis of Pd(OAc)2/Ag2CO3, the C–H arylation takes place at the α-position of the thiopyran ring. When dibromo-substituted compounds are used as reactants, double C–H arylations may occur on the same thiopyran ring at its α- and β-positions. [ABSTRACT FROM AUTHOR]

Thiochalcones undergo cycloaddition reactions in THF solution at 60 °C with the synthetically unexplored 1-phenyl-4H-phosphinin-4-one 1-oxide in a highly regio- and stereoselective manner, yielding hitherto unknown bicyclic P,S-heterocycles containing fused thiopyran and phosphinine rings. The stereochemical structures of two of the obtained (4+2)-cycloadducts were unambiguously assigned by means of the X-ray single-crystal analysis. Based on these assignments, a concerted mechanism of the hetero-Diels–Alder reaction via the preferred endo approach of the heterodiene from the less hindered P=O side of the phosphininone molecule is postulated to explain the established rac-(4RS,8SR,9SR,10SR)-configured (4+2)-cycloadducts isolated as major products. [ABSTRACT FROM AUTHOR]

The development of small molecule anti-tumor drugs has emerged as a promising strategy for cancer treatment, meanwhile the EGFR is associated with tumor formation and progression. In this paper, we designed, synthesized and obtained a series of novel bis-oxidized thiopyran derivatives, and the compound S-16 was identified as the most promising compound for treating NSCLC. A series of experiments (cell cycle, apoptosis assays, in vitro/in vivo animal model and western blotting) were performed to investigate the anti-tumor mechanisms of S-16. The results indicated that S-16 could inhibit A549, H1975 and MCF-7 cancer cells (IC50 of 4, 3.14 and 0.62 μM, respectively), block the cell cycle of H1975 in the G0/G1 phase and induce apoptosis with dose-dependent effects. What is more, the toxicity of S-16 was estimated using the hemolytic test in vitro and H&E staining and blood biochemical analysis in vivo. In addition, H1975 xenograft tumor-bearing BALB/c nude mice were established to evaluate the antitumor activity in vivo, and the results showed that a dose of 80 mg kg−1 of S-16 could inhibit 46.07% tumor growth. These data suggest that S-16 exhibited strong in vitro and in vivo antitumor activity. The molecular docking results also showed that S-16 had a high binding affinity for the EGFR protein. In conclusion, the results of this study suggest that S-16 could be a potential anti-tumor drug for targeting the EGFR. [ABSTRACT FROM AUTHOR]

In this publication, we reported an efficient MOF-based catalytic system for the synthesis of thiopyran and oxospiro-indolinethiopyran derivatives. For the first time, magnetic NH2.MIL-101(Fe)/ED was synthesized through anchoring FeCl3 on CoFe2O4 magnetic nanoparticles surface and then 2-aminoterphthalic acid was used to form MOF structure. In the final step, metal centers were modified with ethylenediamine (ED). Different techniques such as Fourier transmission infrared spectroscopy, X-ray diffraction, Field emission scanning electron microscopy, Transmission electron microscopy, Brunauer–Emmett–Teller analysis, and Thermogravimetric analysis were used to characterize the catalyst structure. Also using X-ray crystallography, the structure of the final product was determined. Nanomagnetic NH2.MIL-101(Fe)/ED gave us a satisfactory answer, affording the corresponding products with high to excellent yields (up to 93% yield). It seems that among the other available procedures, this catalytic system provided higher final product yields which result from the superior activity of this synthesized catalyst. Highlights Designing an efficient basic metal-organic framework catalyst. Novel MOF-based catalytic system for scalable and high-yielding synthesis of thiopyran and oxospiro-indolinethiopyran derivatives. Easy access to important classes of building blocks. Simple work-up procedure, clean reaction profiles and excellent product yields. [ABSTRACT FROM AUTHOR]

A simple method for the synthesis of five- and six-membered ring sulfone carbamates was elaborated. The method includes reaction of the corresponding starting alcohols with trichloroacetyl isocyanate following the hydrolysis of trichloroacetyl protecting group with potassium carbonate in methanol. Rh2(OAc)4 catalyzed cyclization of carbamates was investigated. It was shown that carbamates with saturated sulfone moiety tend to give products of elimination of carbamic acid (corresponding unsaturated sulfones) due to high acidity of C–H bond in α-position of sulfone ring. Unsaturated sulfone carbamate (1,1-dioxido-2,3-dihydrothiophen-3-yl carbamate) in similar reaction conditions afforded new heterocyclic system confirmed by 2D NMR: tetrahydro-3H-4-oxa-2-thia-2b-azacyclopropa[cd]pentalen-3-one 2,2-dioxide. This result can be explained by more favorable aziridination of the double C=C bond by the nitrenoid intermediate compared to the elimination pathway. In silico pharmacological profile of new heterocyclic compound was evaluated. The compound showed good ADME and acute toxicity properties and high probability level of anticancer activity for prostate carcinoma cell line PC-3. [ABSTRACT FROM AUTHOR]

1-(4-substitutesd)-2-(5-phenyl-3-(1H-pyrrol-2-yl)-4,5-dihydropyrazol-1-yl)thiazol-5-yl)-2-aryldiazene 9a-f were prepared through reactions of 5-phenyl-3-(1H-pyrrol-2-yl)-4, 5-dihydropyrazole-1-carbothioamide 5 with hydrazonoyl halides. Furthermore, thioamide 5 was utilized as starting materials for thiazolidone synthesis 10 and arylidene thiazoles 15a–c. Also pyran derivatives 12a-b, 13a-b,14a-b and thioanilide derivaives 16 were obtained from the reaction of thiazilidone 10 with arylidenemalononitrile and phenyl isothiocyanat, respectively. When possible, the structures of experimentally synthesized compounds were identified by elemental analysis, spectral analysis, and alternative synthesis routes. Some of the synthesized compounds as 9f, 10, 12b, and 16 were screened for their cytotoxicity against MCF-7 and HCT-116 cells using the MTT assay. They exhibited remarkable cytotoxic activities with promising IC50 values. Interestingly, compound 16 exhibited potent cytotoxicity against MCF-7 and HCT-116 with IC50 values of 5.05 and 3.08 μM, compared to doxorubicin with IC50 values of 7.27 and 8.92 μM, respectively show interesting biological activities as anticancer activities. Additionally, the tested compounds were nontoxic against WISH cells with higher IC50 values. Hence, these compounds may serve as potent and selective cytotoxic agents. [ABSTRACT FROM AUTHOR]

The use of biodegradable and recyclable deep eutectic solvent (DES) based on choline chloride and urea for the synthesis of 4H-thiopyrans has been reported. The reaction proceeds efficiently under mild conditions without the use of an additional catalyst with better yields. The ease of recovery and reusability of solvent with consistent activity makes this method efficient and environmentally benign. This method is also energy efficient and easy to handle. The synthesized compounds were evaluated for antibacterial activities. The highest antibacterial activity against the tested bacteria Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Salmonella typhi was observed for 2-amino-5-(4-chlorobenzoyl)-4-(4-chlorophenyl)-6-(methylsul-fanyl)-4H-thiopyran-3-carbonitrile. [ABSTRACT FROM AUTHOR]

Benzoylacetone (1) underwent a series of multi-component reactions with aromatic aldehydes and malononitrile or ethyl cyanoacetate to produce the pyran derivatives 4a-f. The latter compounds reacted with malononitrile or ethyl cyanoacetate to yield the condensation products 5a-m. On the other hand, the reaction of 4af with either the diazonium salts 6a-c yielded the arylhydrazone derivatives 7a-i. The multi-component reaction of (1) with aromatic adehydes and cyclohexan-1,3-dione produced the pyran derivatives 9a-c. Compound 1 underwent the Gewald's reactions with elemental sulfur and malononitrile or ethyl cyanacetate yielding the thiophene derivatives 10a,b. Evaluations of the synthesized products were carried out against some selected cancer cell lines and the most active compounds were further evaluated against the seventeen cancer cell lines classified according to the disease. Morphological changes of A549 cell line by the effect of compound 7k was studied using microenvironment of the lung tissue where an excellent results was obtained. [ABSTRACT FROM AUTHOR]

Reaction of thiopyrano[4,3-b]indole-3(5H)-thiones and dimethyl acetylenedicarboxylate (DMAD) proceeds via two competing cascade pathways. Initially, both the pathways begin from thiocarbonyl sulfur and acetylene carbon atoms interaction. Then two parallel processes take place: an alkyne–thiocarbonyl metathesis and a (3 + 2) cycloaddition. In the next stages, in both cases, thiophene ring formation and thiopyran ring opening proceed. Finally, (4 + 2) cycloaddition reactions of intermediate thioketones and a second equivalent of DMAD leads to the resulting thiopyrano[4,3-b]indole derivatives bearing thienyl substituent. The kinetic and thermodynamic characteristics of both pathways were compared on the basis of DFT and ab initio 6-311++G(d,p) quantum chemical calculations. [ABSTRACT FROM AUTHOR]

Despite significant effort, a majority of heavy‐atom‐free photosensitizers have short excitation wavelengths, thereby hampering their biomedical applications. Here, we present a facile approach for developing efficient near‐infrared (NIR) heavy‐atom‐free photosensitizers. Based on a series of thiopyrylium‐based NIR‐II (1000–1700 nm) dyads, we found that the star dyad HD with a sterically bulky and electron‐rich moiety exhibited configuration torsion and significantly enhanced intersystem crossing (ISC) compared to the parent dyad. The electron excitation characteristics of HD changed from local excitation (LE) to charge transfer (CT)‐domain, contributing to a ≈6‐fold reduction in energy gap (ΔEST), a ≈10‐fold accelerated ISC process, and a ≈31.49‐fold elevated reactive oxygen species (ROS) quantum yield. The optimized SP@HD‐PEG2K lung‐targeting dots enabled real‐time NIR‐II lung imaging, which precisely guided rapid pulmonary coronavirus inactivation. [ABSTRACT FROM AUTHOR]

Spiropyrans modified with reactive polyfunctional substituents are of great interest as building blocks for the creation of various smart systems with controllable properties for materials science and biomedicine. In this study, a new highly modified spiropyran of the indoline series, methyl 5′-chloro-8-formyl-5-hydroxy-1′,3′,3′-trimethyl-spiro[chromene-2,2′-indoline]-6-carboxylate, was obtained via the cyclocondensation reaction from 5-chloro-1,2,3,3-tetramethyl-3H-indolium perchlorate and methyl 3,5-diformyl-2,4-dihydroxy-benzoate. The molecular structure of the target compound was confirmed by 1H, 13C NMR, and IR spectroscopy, as well as LC/MS and elemental analysis. Photochemical studies revealed photochromic activity for the obtained spiropyran at room temperature. The photoinduced merocyanine form demonstrated an enhanced lifetime and fluorescent properties in the red region of the spectrum. [ABSTRACT FROM AUTHOR]

Three S‐fused polycyclic aromatic hydrocarbons (PAHs) bearing cyclopenta[b]thiopyran moieties have been designed and successfully synthesized. With the conjugation extension, the absorption onset of the longest PAH reaches 1110 nm. All the three S‐fused PAHs exhibit significant halochromic properties in both solution and solid states. Upon protonation, the proton is incorporated on the cyclopentadiene ring while the positive charge is localized on the thiopyrylium ring. Moreover, no significant difference can be found for the two shorter PAHs upon the protonation by different organic acids, such as trifluoroacetic acid (TFA) and trifluoromethanesulfonic acid (TfOH), while the longest PAH can be only mono‐protonated by TFA but di‐protonated by stronger TfOH. Furthermore, after protonation, the non‐emissive S‐fused PAHs exhibit strong fluorescence and can be regenerated by simply neutralization with triethylamine. The enhanced emission of mono‐protonated products stem from S2→S0 transitions, which disobey the Kasha's rule. [ABSTRACT FROM AUTHOR]

We developed a sulfur-embedding annulative π-extension (thia-APEX) reaction that could construct a sulfur-embedding cationic hexagonal aromatic ring, thiopyrylium, onto unfunctionalized aromatics in one step. The key of thia-APEX is the use of S-imidated ortho-arenoyl arenethiols, and a variety of π-extended thiopyryliums can easily be synthesized. The synthesized thiopyryliums showed diverse absorption and emission properties over the visible light to NIR region, depending on minor structural differences. [ABSTRACT FROM AUTHOR]

Chemoselective annulations of phosphoryl carbenes generated from diazo(aryl)methyl(diaryl)phosphine oxides with pyridinium 1,4-zwitterionic thiolates were performed under microwave irradiation, affording 1-diarylphosphoryl-1H-benzo[c]thiopyran derivatives via [3+3] annulation and indolizine derivatives via ([1+5]-1) annulation with P-Cope elimination as the key step. The annuloselectivity was controlled by the steric hindrance of pyridiniums in pyridinium 1,4-zwitterionic thiolates. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: S‐fused heterocycles have become popular building blocks to construct functional polycyclic compounds. In contrast to the abundant synthetic methodologies for thiophene‐fused aromatics, the synthesis of S‐heterocycles containing six‐membered thiopyran and seven‐membered thiepine rings is much less reported owing to their unfavorable synthetic protocols and the thermal instabilities. Herein, a series of thiepine‐containing polycyclic S‐heterocycles have been successfully synthesized via different synthetic routes which involve initial construction of sulfur bridges and final ring‐closure reactions. Therefore, the dilithium intermediates are excluded, which facilitates the fusion on the thiepine ring with different S‐heterocycles, including thiophene and thiopyran derivatives. Typically, a S‐fused multi‐membered polycyclic compound simultaneously involving thiophen, thiopyran, and thiepine rings has been successfully prepared. Interestingly, nucleus‐independent chemical shift calculations reveal that the incorporated thiopyran and thiepine rings demonstrate aromatic and nonaromatic characteristics, respectively. Moreover, the thermal stabilities of the thiepine derivatives have been tremendously improved after the fusion on the three vinyl groups in the thiepine unit, which is attributed to the enhancements of the activation energies for the S‐extrusion reactions, as revealed by density functional theory calculations. Therefore, our findings not only provide a facile synthetic methodology for S‐fused multi‐membered polycyclic heterocycles, but also furnish a novel construction strategy towards thermally stable thiepine derivatives. [ABSTRACT FROM AUTHOR]

In recent years, magnetic nanoparticles and nanocomposites play an important role as a nanocatalyst in the creation of a wide range of bioactive heterocycles with extraordinarily high activity and selectivity, low energy consumption, and extended life. Among all heterocycles, many natural products, pharmaceuticals, and bioactive compounds contain pyran scaffolds which have a wide range of uses in biomedical research, industry, and medicine. Additionally, these are also widely used in the synthesis of novel heterocyclic systems as precursors. This study focused on recent advances in the last 5 years in using various magnetic recoverable and recycled nanoparticles and nanocomposites to synthesize pyran derivatives and their pharmacological activity. This article has been classified into three subsections: (i) MNPs‐metal nanocomposite catalyzed reactions, (ii) MNPs‐organic based nanocomposite catalyzed reactions, and (iii) MNPs‐ionic liquid nanocomposite catalyzed reactions and (iv) MNPs‐acid based nanocomposite to describe catalytic efficiency of magnetic nanocomposites for the synthesis of pyran derivatives. A comparative study of nanocomposites and different approaches for green synthesis of pyrans by highlighting the advantages and disadvantages along with catalyst recovery and recyclability has been mentioned, which will help scientists to probe and stimulate the study of these scaffolds. [ABSTRACT FROM AUTHOR]

2-Amino-3-cyano-4H-pyran and -thiopyran derivatives were synthesized by three-component reac-tions of aldehydes, dimedone, and CH acids. The molecular and crystal structures of the synthesized compounds were determined by X-ray analysis. [ABSTRACT FROM AUTHOR]

The photophysical properties and a detailed mechanism of the photoinduced ring-opening reactions of benzothiazolinic spiropyran derivatives BTSP–X1-3 (X1–3 = NO2, OMe, and NH2) with the X substituent in the para position as well as an OMe group in the ortho position of the phenolic oxygen atom were investigated at the TD-CAM-B3LYP/6-31G(d) level of theory in gas and solvent media. The environmental effects of the solvent on the transition energies were accounted for by the corrected linear-response (CLR-IEFPCM) formalism in seven steps. Based on the calculated energy barriers, the cis-BTMC → trans-BTMC step is predicted to be the rate-determining step of BTSP to trans-BTMC switching in the excited state. The process of BTSP–X1-3 → BTMC-X1-3 photoswitching in the excited state is predicted to be much faster than in the ground state. From the obtained results, it is predicted that the process of the Cbtspiro–O1 bond dissociation occurs more easily in the more polar solvents and for BTSP-X1 it is easier than the others. In the gas and solvent media, the more populated (bright) state is predicted to be the S2 state for BTSP-X1 and the S1 state for BTSP-X2,3. The redshift in fluorescence wavelength of the trans BTMC-X1-3 on going from polar solvent to nonpolar one is in the range of 31.6 to 66.8 nm for X1 = NO2, 196.2 to 212.3 nm for X2 = OMe and 179.2 to 199.7 nm for X3 = NH2, indicating that its value for X2,3 is greater than X1. [ABSTRACT FROM AUTHOR]

2-Amino-6-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (3) was prepared from the reaction of cyclohexane-1,4-dione with elemental sulfur and malononitrile in 1,4-dioxane and triethylamine as catalyst. The latter compound reacted with triethyl orthoformate and either malononitrile or ethyl cyanoacetate in 1,4-dioxane in the presence of triethylamine to produce 4H-thieno[2,3-f]chromene derivatives 10a,b. In addition, fused pyran and pyridine derivatives were synthesized starting from compound 3. The cytotoxicities of the synthesized compounds were studied using the six cancer cell lines together with c-Met kinase and PC-3 cell line. The most active compounds were tested against five tyrosine kinases and Pim-1 kinase, most of which showed strong inhibition, encouraging further work. [ABSTRACT FROM AUTHOR]

Chiral heterocycles occur in many compounds of interest, but their efficient synthesis is challenging. This study concerns the enantioselective and diastereoselective synthesis of densely substituted chiral pyran derivatives. Diastereodivergence of the oxa‐Diels‐Alder reaction is achieved by using either a bifunctional amino‐thiourea or a monofunctional quinine organocatalyst under ball‐milling conditions. Liquid‐assisted grinding proves a highly efficient means of affording pyrans in high yield, with high enantiomeric purities and short reaction times. [ABSTRACT FROM AUTHOR]

Magnetic nanofiber cellulose (NFC) was selected as a biopolymer surface for the reaction with ferric metformin and a novel nanocatalyst was prepared. This green heterogeneous organometallic catalyst was analyzed by physiochemical techniques. The new metformin drug complex supported on magnetic NFC was used as a powerful and efficient catalyst for the synthesis of functionalized 4H-pyrans derivatives. The antimicrobial activity of the products showed excellent activity against all the bacterial and fungal strains (especially compounds 7q and 6r). [ABSTRACT FROM AUTHOR]

A series of tetrahydrobenzo[b]pyrans derivatives were synthesized with substituted pyrazole carbaldehydes, malononitrile and dimedone by ecofriendly L-proline catalyst in aqueous ethanol. The synthesized compounds were characterized using FTIR, 1H NMR, 13C NMR and Mass spectral techniques. This method holds the advantages of one-pot multicomponent, simple synthetic route, mild reaction conditions, high yield, use of less toxic chemicals and use of eco-friendly catalyst. We also report the study of the synthetic protocol by green chemistry metrics indicates a green relevance. Also, synthesized compounds were screened for their anti-inflammatory and antioxidant activity. Most of the tetrahydrobenzo[b]pyrans derivatives exhibit excellent activity. A series of tetrahydrobenzo[b]pyrans derivatives were synthesized with substituted pyrazole carbaldehydes, malononitrile and dimedone using eco-friendly L-proline as a catalyst in aqueous ethanol. We also report the examination of the synthetic protocol by green chemistry metrics suggests that synthetic protocol has green relevance. Anti-inflammatory activity and antioxidant activity for tetrahydrobenzo[b]pyran derivatives are performed. Some of the synthesized compounds showed excellent anti-inflammatory as well as antioxidant activity. [ABSTRACT FROM AUTHOR]

In the present study, a general approach for the synthesis of 1-(1H-indol-3-yl)-3,3-dimercaptoprop-2-en-1-one (1) and 5-(1H-indol-3-yl)-3H-1,2-dithiole-3-thione (2) was performed. They are currently used as efficient precursors for the synthesis of some new compounds bearing five- and/or six-membered heterocyclic moieties, e.g., chromenol (3, 4), 3,4-dihydroquinoline (7, 8) and thiopyran (10, 12)-based indole core. In addition, molecular docking studies were achieved, which showed that all the newly synthesized compounds are interacting with the active site region of the target enzymes, the targets UDP-N-acetylmuramatel-alanine ligase (MurC), and human lanosterol14α-demethylase, through hydrogen bonds and pi-stacked interactions. Among these docked ligand molecules, the compound (9) was found to have the minimum binding energy (−11.5 and −8.5 Kcal/mol) as compared to the standard drug ampicillin (−8.0 and −8.1 Kcal/mol) against the target enzymes UDP-N-acetylmuramatel-alanine ligase (MurC), and Human lanosterol14α-demethylase, respectively. Subsequently, all new synthesized analogues were screened for their antibacterial activities against Gram-positive (Bacillus subtilis), and Gram-negative bacteria (Escherichia coli), as well as for antifungal activities against Candida albicans and Aspergillus flavus. The obtained data suggest that the compounds exhibited good to excellent activity against bacterial and fungi strains. The compound (E)-2-(6-(1H-indole-3-carbonyl)-5-thioxotetrahydrothieno [3,2-b]furan-2(3H)-ylidene)-3-(1H-indol-3-yl)-3-oxopropanedithioic acid (9) showed a high binding affinity as well as an excellent biological activity. Therefore, it could serve as the lead for further optimization and to arrive at potential antimicrobial agent.

A simple and environmentally friendly method to prepare S-heterocycles by cyclization of aromatic thiols and diols with H2 O as a byproduct is described. The Sc(OTf)3-catalyzed dehydrative cyclizations of aromatic thiols and diols provided the corresponding thiopyran and thiophene derivatives. Control experiments were also performed to obtain insights into the reaction pathway [ABSTRACT FROM AUTHOR]

3-Chloro-3-chlorosulfenyl-4′-methylspiro[chroman-2,1′-cyclohexane]-4-one (4) was prepared from the reaction of spiro 4′-methylcyclohexan-1′,2-chroman-4-one (3) with thionyl chloride according to reported method. Furthermore, treatment of compound 4 with potassium iodide gave 1,2-bis (3-chloro-4′-methylspirochroman-2,1′-cyclohexyl-4-one)disulfane (6) in addition to 4,4‴-dimethyltrispiro[cyclohexane-1,2′-chroman-3′,2″-2H-chromeno[3,4-e][1,3,4]-oxadithiin-5″,1‴-cyclohexan]-4′-one (5). The formation of compound 5 could be presumably explained via the formation of unstable intermediate oxo-thioketone A. The formation of the latter intermediate A was confirmed chemically through the thermal reaction of compound 5, or compound 6 with 1,3-homodiene such as: 1,3-cyclohexadiene, isoprene, and 2,3-dimethyl-1,3-butadiene to afford the products 7–9, respectively. The chemical structures of the newly prepared compounds were confirmed by spectroscopic methods (IR, 1H & 13C NMR, and MS). The synthesized compounds were evaluated against lung (A549), prostate (PC3), pancreatic (PACA2), and breast (MDA) cancer cell lines. Compound 3 exhibited prominent cytotoxicity against A549, PC3, and PACA2 cancer cell lines with IC50 values from 12.4 to 16.1 µM, which was comparable or superior to the reference drug (Doxorubicin). Compounds 7–9 showed better cytotoxicity against breast (MDA) cancer cell line than the reference drug (Doxorubicin). [ABSTRACT FROM AUTHOR]

Three-component condensation of in situ generated pyridinium aroylmethylides with isatins or aromatic aldehydes and cyclic 1,3-dicarbonyl compounds gave a series of condensed 2-aroyl-2,3-dihydrofurans. The reaction proceeds diastereoselectively and represents a cascade process involving the Knoevenagel condensation, the carbo-Michael reaction, and intramolecular nucleophilic substitution. The possibility of reductive rearrangement of spirocyclic furanyl-substituted oxindole into a pyran derivative by the action of zinc in acetic acid was shown. [ABSTRACT FROM AUTHOR]

Design of some novel functionalized thiophene, thieno[2,3-b]thiophene, thiopyran and thiopyrano[2,3-b]thiopyran bearing phosphonate groups was described in one-pot through simple two steps. The methodology depended on the reaction of three-component of chloroacetyl chloride with triethyl phosphite in the presence of sodium 2,2-dicyanoethene-1,1-bis(thiolate) or sodium (2,2-dicyano-1-methylthioethen-1-yl)thiolate in a certain sequence. [ABSTRACT FROM AUTHOR]

Polyurethanes represent a versatile class of polymers and are one of the most employed in the thermoset market. However, due to their thermodynamically stable carbamate bond, they suffer from a lack of reprocessability, recyclability, and degradability, and are therefore usually discarded after use. Recently, transcarbamoylation in polyurethane thermosets has been demonstrated via associative exchange in the presence of a strong organic acid. Intending to introduce spatiotemporal control in the processability of polyurethane materials, in this work we investigate dynamic transcarbamoylation by the addition of a latent acidic catalyst into an aromatic and an aliphatic polyurethane network. We introduce three photoswitches based on merocyanine/spiropyran compounds which, upon exposure to visible light, undergo a reversible cyclization reaction, resulting in the formation of strong acids. The use of such photoswitches prevents the presence of a permanent acidic species in the network, which would eventually lead to its degradation over time. Importantly, due to the reversible nature of the cyclization reaction, the release of the acidic catalyst is not permanent, as evidenced by stress relaxation measurements. Overall, the evidence of the light-induced, acid-catalyzed transcarbamoylation is supported by stress relaxation, optical microscopy, and self-healing measurements. [Display omitted] • Reversible Spiropyran photoswitches can catalyze the dynamic transcarbamoylation in polyurethanes. • The use of such photoswitches prevents the presence of a permanent acidic species in the network, preventing degradation over time. • Due to the reversible nature of the photoswitch, the release of acid is not permanent, as evidenced by stress-relaxation measurements. [ABSTRACT FROM AUTHOR]

Herein, we present a new one-pot procedure for the 3,6′-dithionation of pomalidomide derivatives in which the key 3-position sulfur atom is preferentially installed at the desired (but sterically congested) carbonyl of the aminophthalimide system and with regiochemistry distinct from Lawesson's Reagent thionation methods. When heated in 1,4-dioxane with P4 S10 –pyridine complex, pomalidomides are smoothly and reproducibly converted into their 3,6′-dithionated analogues in roughly 30% isolated yield and at various scales. While detrimental to the desired 3,6′-type outcome when employing Lawesson's Reagent, we hypothesize that the pomalidomide aniline group instead facilitates P4 S10-type thionation at the otherwise hindered 3-position carbonyl, contributing to the selectivity observed. When paired with classical methods of thionation, this approach offers an interesting and appealing addition to the synthetic toolbox, permitting facile late-stage access to complementary thionated pomalidomides in direct single-flask procedures. [ABSTRACT FROM AUTHOR]

We represent here, a divergent approach for the total synthesis of (±)‐Mahanine and twelve other naturally occurring carbazole alkaloids. Remarkably, we have utilized a simplified scalable Suzuki coupling for C−C bond formation and a metal‐free C−N coupling sequence to synthesize the functionalized carbazole scaffold from a single intermediate. Subsequently, either functional group manipulations or late‐stage pyran ring annulation furnished a library of 13 carbazole alkaloids mostly isolated from a traditional medicinal plant Murraya koenigii. The construction of carbazole moiety at the initial‐stage followed by late‐stage pyran annulation under mild condition overcomes the decomposition problem of pyran‐ring under acidic or other harsh reaction conditions. [ABSTRACT FROM AUTHOR]

The reaction of β-keto sulfones and β-keto sulfonamides bearing an unsubstituted α-methylene unit with (diethylamino) sulfur trifluoride (DAST) and morpholinosulfur trifluoride (morphDAST) led to α-fluoro-α-(dialkylamino)thio-β-keto sulfones (sulfonamides). For the β-keto sulfonamides bearing an α-methyl substituent, the Cα Cβ bond cleavage was observed upon reaction with DAST reagents, resulting in formation of (αfluoro-α-(dialkylamino)thio)ethyl sulfonamides. The structure of the products was confirmed by an X-ray diffraction study, and mechanistic insights of the process have been presented. [ABSTRACT FROM AUTHOR]

The synthesis of nitrogen- and oxygen-containing heterocycles has found many applications in the preparation of biomedical intermediates, yet actual synthetic procedures display limitations such as high-loading catalysts, harsh reaction conditions and tedious preparation of heterogeneous catalysts. Alternatively, photocatalysis allows to access functional products with minimum synthetic procedures and waste generation. Here, we present an efficient, simple, green protocol for the synthesis of N- and O-containing six-membered-ring compounds under mild conditions under visible blue light. Various aldehydes and 1,3-diketones can be reacted to afford eight series of corresponding 1,4-dihydropyridines and 4H-benzo[b]pyrans. This protocol has some merits such as the use of abundant and sustainable aqueous ethanol as solvent, short reaction time (within 60 min), no need of catalyst and broad functional group tolerance to afford 81 different series of target molecules in 75–96% yield under mild conditions. [ABSTRACT FROM AUTHOR]

A new series of marcocyclic ligands, 1,2,4,5,9,10,12,13‐octaaza[16]annulene derivatives were synthesized by using the condensation reaction of the correspondingly [2+2] 2‐heteroaryl‐substituted vinamidinium salts or phenyl vinamidinium salts and derivatives or halo‐substituted vinamidinum salt [1A‐10A] with thiocarbohydrazide in ethanolic medium under mild condition. Metal complexes were formed by reacting of ethanolic solution of Co, Ni, and Zn with macrocyclic ligand in ethanolic medium under mild condition. Purposed complexes have been characterized with the help of elemental analyses, comparative absorption band of ν(C=N), mass, and NMR. Geometry and complex formulation are out of scope of this work. The biological activities of carohydrazide and thiocarbohydrazide base of the ligands and purposed complexes such as antimicrobial, antitumor, and insecticides have attracted significant attention in bioorganic chemistry. [ABSTRACT FROM AUTHOR]

α‐Ketothioesters undergo triphenylphosphine (PPh3)‐catalyzed cyclization with acetylenedicarboxylate esters smoothly, in contrast to α‐ketooxoesters which require more drastic conditions with the limited substrate scope. The reaction works well with a wide range of α‐ketothioesters, delivering highly functionalized α,β‐unsaturated γ‐butyrolactones in moderate to excellent yields. The higher reactivity of the thioester derivatives is seemingly due to a favourable intramolecular non‐bonding electrostatic 1,4‐interaction involving C−S σ* orbital on the sulphur atom and the lone pair of electrons in the electron‐donating oxygen atom. This is apparent from the X‐ray crystallographically determined internuclear distance between the sulphur and ketone (C=O) oxygen atoms (2.71–2.85 Å), which is significantly less than the sum of their van der Waals radii (3.25–3.30 Å). The substitution on the S atom is oriented diametrically away from the ketone O atom to maximize the interaction between them. The trend is also seen in the 1,4‐S⋅⋅⋅O contact between the S and furan O atoms (2.70 Å) in the γ‐butyrolactone products. [ABSTRACT FROM AUTHOR]

In this work the multi-component reactions of either of the arylhydrazocyclohexan-1,3-dione derivatives 3a--c with either of benzaldehyde (4a), 4-chlorobenzaldehyde (4b) or 4-methoxybenzaldehyde (4c) and either malononitrile (5a) or ethyl cyanoacetate (5b) giving the 5,6,7,8-tetrahydro-4H-chromene derivatives 6a--r, respectively, are presented. The reaction of two equivalents of cyclohexan-1,3-dione with benzaldehyde gave the hexahydro-1H-xanthene-1,8(2H)-dione derivative 7. On the other hand, the multi-component reactions of compound 1 with dimedone and benzaldehyde gave 13. Both of 7 and 13 underwent heterocyclization reactions to produce fused thiophene, pyran and thiazole derivatives. Selected compounds among the synthesized compounds were tested against six cancer cell lines where most of them gave high inhibitions; especially compounds 3b, 3c, 6b, 6c, 6d, 6f, 6i, 6m, 6n, 8b, 14a, 15 and 16 being the most cytotoxic compounds. Further tests against the five tyrosine kinases c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR and Pim-1 kinase showed that compounds 3c, 6c, 6d, 6f, 6n, 14a and 15 were the most potent of the tested compounds toward the five tyrosine kinases and compounds 3c, 6c, 6d, 6n and 15 displayed the highest inhibitions toward Pim-1 kinase. [ABSTRACT FROM AUTHOR]

One‐pot four‐component reactions of phenacyl bromides, parabanic or thioparabanic acids, thiophenols, and triphenylphosphine in the presence of triethylamine afforded new derivatives of hydantoin or thiohydantoin in good to high yields (65%‐90%). Their antibacterial activities were evaluated against two Gram‐positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two Gram‐negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Among the synthesized compounds, the obtained products from 2‐hydroxythiophenol exhibited higher antibacterial activity than those obtained from 2‐aminothiophenol. Compound 9l including N,N′′‐diphenyl thiohydantoin moiety showed the highest antibacterial activity (26.0 ± 01.4) against B subtilis, in comparison with other synthesized samples. The antioxidant activities of the synthesized hydantoins and thiohydantoins were investigated by DPPH radical‐scavenging based on Blois method. The results showed that all the compounds have high DPPH inhibition potency (77.4%‐83.9%) that it could be due to existence of heteroatoms with lone pair electrons and exchangeable protons on their NH2 and OH groups. [ABSTRACT FROM AUTHOR]

This minireview summarizes important collection of cycloaddition strategies that were used for the synthesis of sulfur‐containing five‐ and six‐membered heterocycles from thiocarbonyl‐based synthons. Among various stepwise or concerted methods available to prepare thioheterocycles, cycloaddition reactions of thiocarbonyls in particular present an important class of reaction owing to their ability to function as super dipolarophiles and/or superdienophiles. Design and development of various reactions in recent years with thiocarbonyls have certainly superseded the general purview on this reactive synthon that it often leads to side reaction and oligomerization. This article, apart from including the advances in the known reaction manifold of thiocarbonyls, also provide updates on new developments of cycloaddition chemistry, which includes donor‐acceptor (D−A) cyclopropanes and azaoxyallyl cation as 1,3‐dipolar reaction partners. This review should serve the purpose of an important guiding tool for organic and medicinal chemist to design and develop new class of cycloaddition or related transformations with thiocarbonyls for the preparation of novel heterocycles. [ABSTRACT FROM AUTHOR]

The reactions of 3-perfluoroacyl-4Н-chromenes and 2-perfluoroacyl-1Н-benzo[f]chromenes with primary aromatic amines resulted in pyran ring cleavage, which was initiated by an aza-Michael reaction. The obtained enamino ketones underwent rearrangements in the presence of superacids, giving 2-perfluoroalkyl-4Н-chromene-3-carbaldehydes and 3-perfluoroalkyl-1Н-benzo[f]chromene-2-carbaldehydes, respectively. [ABSTRACT FROM AUTHOR]

A series of ethyl 4-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]-1-aryl-1H-pyrazole-3-carboxylates was obtained as a result of the reaction of ethyl 4-formyl-1-aryl-1H-pyrazole-3-carboxylates with rhodanine. Under the action of NaOH, the prepared pyrazole-3-carboxylates underwent recyclization to form 2-aryl-7-oxo-2,7-dihydrothiopyrano[3,4-c]pyrazole-5-carboxylic acids—the first representatives of new heterocyclic system. [ABSTRACT FROM AUTHOR]

An efficient and viable one‐pot protocol for the synthesis of a specific class of 2‐thioxothiopyrano[3,2‐c] chromen‐5(2H)‐ones has been devised by the cross‐coupling of 4‐hydroxycoumarin and α‐enolic dithioesters under metal‐ and additive‐free conditions in open air. The reaction proceeds via in situ generation of 4‐chloro‐3‐formylcoumarin followed by consecutive Michael‐type addition/intramolecular cyclization/ elimination cascade, enabling the creation of thiopyran‐2‐thione ring over coumarin framework through successive formation of C−C and C−S bonds. Remarkably, the benign conditions, atom‐economy, and quantifying forbearance of a wide horizon of functional groups are added characteristics to this strategy. [ABSTRACT FROM AUTHOR]

[Display omitted] A Sc(OTf) 3 -catalyzed diastereoselective [4 + 2] cycloaddition reaction of 3-benzylideneindoline-2-thiones with 2-alkylidene malonates has been realized, leading to biologically important indole-annulated thiopyran derivatives in moderate to good yields. Moreover, a gram-scale reaction and chemical transformation of the cycloadduct into a sulfone were carried out to further extend the synthetic utility. [ABSTRACT FROM AUTHOR]

From many decades, S -heterocycles have maintained their status as an important part and core of FDA approved drugs and medicinally active compounds. With exhaustive exploration of nitrogen heterocycles in medicinal chemistry, researchers have shifted their interest towards other heterocycles, especially, S -heterocycles. Thus several attempts have been made to synthesize a variety of new sulphur containing compounds with high medicinal value and low toxicity profile, in comparison to previous N -heterocycles. Till today, S -heterocycle containing compounds have been largely reported as anticancer, antidiabetic, antimicrobial, antihypertension, antivral, antinflammatory etc. In this review, the authors have tried to provide a critical analysis of synthesis and medicinal attributes of sulphur containing heterocycles such as thiirane, thiophene, thiazole, thiopyran, thiazolidine etc reported within last five years to emphasize the significance and usefulness of these S -heterocycles in the drug discovery process. Image 1 • This review compiles various S- heterocycles such as thiazole, thiazolidine, thiophene, thiopyran etc. • This review focused on various synthetic strategies of sulphur containing heterocycles. • Various pharmacological activities of S -containing heterocycles have been compiled together. • SAR and in-vitro studies of S -heterocycles have been discussed in details. [ABSTRACT FROM AUTHOR]

S- and Se-heteroarenes containing cyclopenta[b]thiopyran and/or cyclopenta[b]selenopyran moieties have been synthesized via PtCl2-catalyzed ring-expanding cycloaromatizations. Intervalence charge transfer bands can be observed for the three heteroarenes upon chemical oxidation, suggesting the electronic communication between S- and/or Se-fused aromatics. [ABSTRACT FROM AUTHOR]

A mononuclear complex [Cu(HL·S)2(NO3)2] (1) and a one‐ dimensional coordination polymer [Cu(HL·S)Cl2]n (2) [HL·S = 4‐(pyridin‐2‐ylmethyl)tetrahydro‐2H‐thiopyran‐4‐ol] showcase the structure‐directing role of the counterions in their formation reaction: monodentate ligation of NO3– and Cl– induces an octahedral (with two HL·S per Cu in 1) or trigonal‐bipyramidal (with one HL·S per Cu in 2) CuII coordination environment. In contrast to 1 exhibiting no coordinative metal–sulfur bonds in the crystal lattice (space group P21/c), 2 (P21/c) features intermolecular Cu–S contacts of 2.3188(7) Å. The coordination compounds are thermally stable up to ca. 160 °C. Whereas 1 demonstrates the spin‐like behavior of an isolated central CuII ion, compound 2 exhibits weak antiferromagnetic intra‐chain coupling with J ≈ –2.1 cm–1 between neighboring CuII ions. [ABSTRACT FROM AUTHOR]