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Conventional semiconductor photocatalysts produce superoxide and hydroxyl radicals as the major reactive oxygen species (ROS). Here, we report that Ag/Ag3PO4 catalyst efficiently generates singlet ...

A visible-light-driven multistep tandem reaction between vinyl azides and alkyl bromides has been developed leading to the formation of tetralone skeletons under mild conditions, which can be easily scaled up to the gram scale. Various 1-tetralone derivatives are synthesized and transformed into desired products in good to high yields.

Substituted tetralones such as 3,3,6,8-tetramethyl-1-tetralone undergo photoenolization to produce a photoenol excited state with a lifetime around ~ 3 μs, which involves the carbonyl triplet state of the ketone (τ ~ 1.9 ns), as a precursor; the excited photoenol also has biradical character and is useful for the fast synthesis of gold nanostructures. In the case of excited photoenols like this one, if metal ion trapping fails, they return to the original ketone precursor and remain available for future events that can lead to the target nanoparticles. This study includes the characterization of the photochemistry of the substituted tetralone, and the dual behavior of reaction intermediates, as biradicals and excited states, in energy and electron transfer processes.

Fourteen eremophilane sesquiterpenoids (1-14), including nine new congeners, septoreremophilanes A-I (1-9), together with three known sesquiterpenes (15-17), two known tetralone derivatives (18, 19), and two known cholesterol analogues (20, 21), were isolated from the endophytic fungus Septoria rudbeckiae. Compounds 1-6 and 7a belong to the family of the highly oxygenated eremophilane sesquiterpenoids with a 6/6/5 tricyclic system and bearing a hemiacetal moiety. The inhibitions of all metabolites against eight bacteria were estimated in vitro, and nine new metabolites (1-9) were tested for antineuroinflammatory activity. Notably, the effects of 4 against Pseudomonas syringae pv. actinidae and 20 against Bacillus cereus displayed potent inhibitory, with the MIC values of 6.25 and 6.25 μM, respectively. Further, scanning electron microscopy analyses indicated that 4 and 20 were to change the outer configuration of bacterial cells, respectively, and the investigations demonstrated that 4 and 20 may act as potential structure templates for the development of the agrochemical bactericides. Additionally, compound 6 displayed potent inhibition of NO generation in lipopolysaccharide-induced BV-2 microglial cells (IC50 = 12.0 ± 0.32 μM), and the conceivable anti-inflammatory mechanisms implicated were also investigated by molecular docking. Thus, the bioactive metabolites of the strain S. rudbeckiae may serve as a novel resource to be developed.

Atropo‐enantioselective biaryl coupling through C−H bond functionalization is an emerging technology allowing direct construction of axially chiral molecules. This approach is largely limited to electrophilic coupling partners. We report a highly atropo‐enantioselective C−H arylation of tetralone derivatives paired with aryl boronic esters as nucleophilic components. The transformation is catalyzed by chiral cyclopentadienyl (Cpx) iridium(III) complexes and enabled by oxidatively enhanced reductive elimination from high‐valent cyclometalated Ir‐species., A highly atropo‐enantioselective C−H arylation of tetralone derivatives paired with aryl boronic esters as nucleophilic components is presented. The transformation is catalyzed by chiral cyclopentadienyl (Cpx) iridium(III) complexes and enabled by oxidatively enhanced reductive elimination from high‐valent cyclometalated Ir‐species.

Background and purpose: Tyrosinase enzyme has a key role in melanin biosynthesis by converting tyrosine into dopaquinone. It also participates in the enzymatic browning of vegetables by polyphenol oxidation. Therefore, tyrosinase inhibitors are useful in the fields of medicine, cosmetics, and agriculture. Many tyrosinase inhibitors having drawbacks have been reported to date; so, finding new inhibitors is a great need. Experimental approach: A variety of 6-hydroxy-3,4-dihydronaphthalenone chalcone-like analogs ( C1 - C10 ) have been synthesized by aldol condensation of 6-hydroxy tetralone and differently substituted benzaldehydes. The compounds were evaluated for their inhibitory effect on mushroom tyrosinase by a spectrophotometric method. Moreover, the inhibition manner of the most active compound was determined by Lineweaver-Burk plots. Docking study was done using AutoDock 4.2. The drug-likeness scores and ADME features of the active derivatives were also predicted. Results/Findings: Most of the compounds showed remarkable inhibitory activity against the tyrosinase enzyme. 6-Hydroxy-2-(3,4,5-trimethoxybenzylidene)-3,4-dihydronaphthalen-1(2H)-one ( C2 ) was the most potent derivative amongst the series with an IC 50 value of 8.8 μM which was slightly more favorable to that of the reference kojic acid (IC 50 = 9.7 μM). Inhibitory kinetic studies revealed that C2 behaves as a competitive inhibitor. According to the docking results, compound C2 formed the most stable enzyme-inhibitor complex, mainly via establishing interactions with the two copper ions in the active site. I n silico drug-likeness and pharmacokinetics predictions for the proposed tyrosinase inhibitors revealed that most of the compounds including C2 have proper drug-likeness scores and pharmacokinetic properties. Conclusion and implications: Therefore, C2 could be suggested as a promising tyrosinase inhibitor that might be a good lead compound in medicine, cosmetics, and the food industry, and further drug development of this compound might be of great interest.

A formal synthesis of (±)-cochlearol A was accomplished. The synthesis features Suzuki coupling and Friedel-Crafts cyclization as a convergent strategy to the functionalized tetralone ring and an intramolecular construction of the C/D ring involving sequential epoxide formation/acetal formation.

A practical and scalable route to (3aR, 9bR)-8-fluoro-7-(perfluoropropan-2-yl)-9b-(phenylsulfonyl)-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole 10, an advanced intermediate en route to the synthesis o...

Substituted tetralones have played a substantial role in organic synthesis due to their strong reactivity and suitability as a starting material for a range of synthetic heterocyclic compounds, pharmaceuticals along with biological activities as well as precursors of many natural products and their derivatives. Many α-tetralone derivatives are building blocks that have been used in the synthesis of therapeutically functional compounds like some antibiotics, antidepressants, acetylcholinesterase inhibitors effective for treating Alzheimer’s disease and alkaloids possessing antitumor activity. In this review, there has been an attempt to explore the small molecule library having an α-tetralone scaffold along with their diverse biological activities. Structural features of α- tetralone derivatives responsible for potential therapeutic applications are also described.

A series of transition metal (II) complexes with general formula [M(L1−4)2(H2O)2] (where M = Co(II), Ni(II), Cu(II) and Zn(II)) was synthesized by the reaction of metal(II) acetates with hydrazones [HL1–HL4] obtained from condensation of tetralone with hydrazide derivatives. The characterization of synthesized compounds (1–20) was done by using elemental analysis, different spectral studies (UV–Vis, 1H NMR, 13C NMR, FT-IR, mass, ESR and fluorescence), magnetic susceptibility, molar conductance measurement and thermal (DTA, TGA and DTG) analysis. The characterization results suggested the bidentate nature of the hydrazones, which chelate with the metal ion via nitrogen of (C=N) group and deprotonated carbonyl oxygen in the enolized form, resulting in stable, non-volatile octahedral complexes. The antimicrobial potential of the compounds was evaluated against four bacterial, i.e. (S. aureus, B. subtilis, P. aeruginosa and E. coli), and two fungal species, i.e. (A. niger and C. albicans), by a serial dilution method with complexes 15 and 16 as most active compounds against microbes. All the compounds were also tested for its cytotoxicity (in vitro) against three human cancer cell lines (A549, HeLa and MCF-7) and one normal cell line (L6) by the MTT assay, which focussed on an increased activity of compounds 7 and 15 towards A549, MCF-7 and HeLa cancer cell line with IC50 values ranging from 10.76 to 16.42 μg/mL, and compounds were found to be non-toxic towards L6 cell line as compared to the standard drug doxorubicin. The results demonstrated that complexation enhanced the biological activity of compounds. The synthesized compounds (1–20) were screened for antitumor activities against A549, MCF7, Hela cancer cell lines. Copper complex (7) and (15) was found to be the most active antitumor agent and less toxic against L6—Rat myoblast normal cell line than standard doxorubicin.

Here we report a highly efficient room-temperature afterglow system based on difluoroboron β-diketonate (BF2bdk) dopants and tetralone matrices. The BF2bdk compounds have been synthesized by an efficient cascade reaction from aromatic substrates and exhibit high photoluminescence quantum yield in both solution and solid state. Upon doping, BF2bdk-tetralone materials at room temperature have been shown to display greenish yellow afterglow emission that can last for 4 s and to possess an afterglow quantum yield up to 26% under ambient conditions, which is among the highest yields of the reported dopant–matrix organic afterglow systems. After being ground into aqueous suspension with the aid of an aqueous solution of amphiphilic block copolymers, the BF2bdk-tetralone materials have been found to retain their afterglow properties, show capability in avoiding the interference of a strong fluorescence background, and exhibit both ex vivo and in vivo high-contrast bioimaging functionalities.

We report an enantioselective phase transfer α-chlorination of β-keto esters catalyzed by hybrid amide-based Cinchona derivatives. The chlorination process proceeds with proper quantitative yields (up to

C18H17NO3, triclinic, P 1 ‾ $P‾{1}$ (no. 2), a = 4.0929(4) Å, b = 12.9527(11) Å, c = 14.4228(12) Å, α = 70.171(8)°, β = 87.229(8)°, γ = 87.567(8)°, V = 718.16(12) Å3, Z = 2, R gt (F) = 0.0549, wR ref (F 2) = 0.1526, T = 99.9(3) K.

An appropriate and efficient Q-tube-assisted palladium-catalyzed strategy for the synthesis of novel, unparalleled diaza-dibenzo[a,e]azulene and diaza-benzo[a]fluorene derivatives has been sophisticated, which includes oxygen and AcOH-induced oxidative C(sp3)-C(sp2) cross-dehydrogenative coupling reactions of 1-amino-2-imino-4-arylpyridine-3-carbonitriles with benzocyclic ketones such as benzosuberone, tetralone, thiochromone, and chromone, respectively. This Q-tube gas purging kit assisted-protocol features safe due to easy pressing and sealing, a wide substrate scope, easy workup and purifying phases, and the use of O2 as a benign oxidant, in addition to being scalable and having a high atom economy. The suggested mechanistic pathway includes a formal dehydrative step followed by palladium AcOH-induced CH(sp3)-CH(sp2) oxidative cross-coupling. In this study, X-ray crystallographic analysis has been used to authenticate the targeted products.

The reaction of 5-phenylpenta-2,4-dienoic acid with benzene in CF3SO3H, depending on the reaction conditions, gives three products, namely, 5,5-diphenylpent-2-enoic acid and tetralone and indanone derivatives. These carbocyclic compounds are formed through the addition of two benzene molecules to the starting diene acid and subsequent intramolecular acylation.

Background: Tetralone derivatives, important resources for the development of new drugs which can act in the treatment of central nervous system disorders or participate in synthesis reaction for the synthesis of various pharmaceuticals, have great research value and a bright prospect in exploitation. Methods: A novel chiral HPLC method for efficient enantioseparation of eight tetralone derivative enantiomers was developed on cellulose based CHIRALPAK IC chiral stationary phase under normal mode by investigating the effects of type and content of organic modifier, column temperature and flow rate on retention and enantioselectivity. Besides, the specificity, linearity, stability, precision, accuracy and robustness of this method were also validated. Results: Satisfactory enantioseparation was obtained for all enantiomers in n-hexane/2-propanol mobile phase system at ambient temperature. The thermodynamic study indicated that the solute transfer from the mobile to stationary phase was enthalpically favorable, and the process of enantioseparation was mainly enthalpy controlled. This method met the requirements for quantitative determination of tetralone derivative enantiomers. Conclusion: This study can provide great and important application value for enantioseparation of eight pairs of newly synthesized tetralone derivative enantiomers under normal mode using CHIRALPAK IC chiral column.

The compound 4-hydroxy-α-tetralone (1) has been reported to possess potent anti-tubercular, anti-diabetic and anti-leishmanial activities. In our earlier studies the compound 1 and its various semi-synthetic derivatives showed potent bioenhancing activity in combination with nalidixic acid (NAL) and tetracycline (TET) reducing the minimum inhibitory concentration (MIC) of antibiotics up to 8 folds by inhibition of ABC efflux pump. However, in gram negative bacteria, resistance nodulation division (RND) family are considered as major efflux pump responsible for multidrug resistance (MDR). Hence, the current study was carried out to access the in-silico docking potential of compound 1 and its cinnamoyl (1a), 3, 4, 5-trimethoxybenzoyl (1b) derivatives against RND efflux pump target proteins AcrA, AcrB, TolC of E. coli. The docking study showed that the test compounds have good binding affinity with target proteins. The derivative 1a showed highest interaction with AcrA followed by AcrB showing binding energies -8.7 and -8.2 kcal/mol respectively. The low molecular weight ≤500, high hydrogen bonding, high log p value (>1) with hydroxy, methoxy and aromatic group of ligands make these compounds as effective efflux pump inhibitor. In drug likeliness studies, these compounds pass the safety criteria with enhanced bioavailability and absorption, less acute oral toxicity, less hepatotoxicity. This study promises that the compound 1 and its derivatives (1a & 1b) might be RND efflux pump inhibitors providing the initial platform for development of safer and cost-effective antibacterial drug to manage MDR infections.

To show the synthetic utility of the catalytic C-C activation of less strained substrates, described here are the collective and concise syntheses of the natural products (-)-microthecaline A, (-)-leubehanol, (+)-pseudopteroxazole, (+)-seco-pseudopteroxazole, pseudopterosin A-F and G-J aglycones, and (+)-heritonin. The key step in these syntheses involve a Rh-catalyzed C-C/C-H activation cascade of 3-arylcyclopentanones, which provides a rapid and enantioselective route to access the polysubstituted tetrahydronaphthalene cores presented in these natural products. Other important features include 1) the direct C-H amination of the tetralone substrate in the synthesis of (-)-microthecaline A, 2) the use of phosphoric acid to enhance efficiency and regioselectivity for problematic cyclopentanone substrates in the C-C activation reactions, and 3) the direct conversion of serrulatane into amphilectane diterpenes by an allylic cyclodehydrogenation coupling.

The rhodium-catalyzed cycloisomerization of ester-tethered 1,6-diynes bearing a cyclopropanol moiety produced tetralone/exocyclic diene hybrid molecules with thermodynamically unfavorable alkene geometry. The results of control experiments and density functional theory calculations suggest that the ester tether plays an important role in the efficiency of E/Z isomerization processes.

The remote C(sp3)–H functionalization enabled by a radical-mediated 1,5-hydrogen-atom transfer (HAT) process using vinyl azides and 1,4-dihydropyridines as precursors has been described. In this study, 1,4-dihydropyridines can function as 1,2-diradical synthons through sequential homolytic cleavage of an ipso-C–C bond and a β-C(sp3)–H bond. This reaction offers facile access to a diverse range of α-tetralones with excellent stereoselectivity. The utility of the present method is further highlighted by its application to rapid assembly of the tetracyclic scaffold present in furanosteroids as well as the synthesis of aromatic amines.

Phytochemical investigation and chromatographic separation of extracts from the aerial parts of Dianella ensifolia (L.) DC. (synonym Dianella nemorosa Lam. Ex. Schiler f.) led to the isolation of 10 compounds, the structures of which were determined by HR-ESI-MS and 1 D- and 2 D-NMR spectroscopies, and by comparisons with published studies. Among the isolated compounds were three flavans, a biflavan, a biflavone, a tetralone, a naphthalen glycoside, an aromatic compound, and two steroids. Six of these were known chemicals, while three were identified as new compounds: 7-acetyl-4R,8-dihydroxy-6-methyl-1-tetralone, 2(S),2′,4′-dihydroxy-7-methoxyflavan, and diaensi-biflavan. 2(S),7,4’-dimethoxy flavan was obtained for the first time as a natural product.

International audience; The tetralone and tetralone derivatives, as crucial structural scaffolds of potential novel drugs targeted at multiple biological end-points, are normally found in several natural compounds and also, it can be used as parental scaffold and/or intermediate for the synthesis of a series of pharmacologically active compounds with a broad-spectrum of bioactivities including antibacterial, antitumor, CNS effect and so on. Meanwhile, SAR information of its analogues has drawn attentions among medicinal chemists, which could contribute to the further research related to tetralone derivatives aimed at multiple targets. This review encompasses pharmacological activities, SAR analysis and docking study of tetralone and its derivatives, expecting to provide a general retrospect and prospect on tetralone derivatives.

In this study, the co-culture of Nigrospora oryzae and Beauveria bassiana, the pathogenic endophytes in the seeds of Dendrobium officinale, were examined for their antagonistic relationship by the production of metabolite. One new chlorotetralone (1) and five known compounds, murranoic acid A (2), 9,12,13-trihydroxy-10-octadecenoic acid (3), 3,3′-methylenebis(4-hydroxy-6-methyl-2H-pyran-2-one) (4), sclerin (5), and (4S)-4,6,8-trihydroxy-3,4-dihydro-1(2H)-naphthalen-1-one (6), were isolated. Compounds 1–5 showed antifungal activity against B. bassiana with MICs of 256, 128, 2, 32, and 64 μg/mL, and N. oryzae with MICs of 64, 256, 256, 256, and 64 μg/mL. Compound 4 showed significant antifungal activity against co-culture of B. bassiana and N. oryzae with MIC at 1 μg/mL.

A series of (aMnOx–CoOy)r/γ-Al2O3 catalysts with different molar ratio of metal and supports (r denotes as the molar ratio of metal and supports, r = 0.02,0.03,0.04,0.05,0.06,0.08) and varied metal molar ratio(a stands for the molar ratio of Mn:Co, r = 1/3,1/1,3/1,6/1,1/0) were fabricated through impregnation route and characterized using X-ray diffraction (XRD), Inductively coupled plasma-atomic emission spectrometry (ICP-AES), N2 adsorption–desorption, X-ray photoelectron spectroscopy (XPS), H2 temperature programmed reduction (H2-TPR) and Scanning emission microscope (SEM). Among the catalysts investigated, (3MnOx–CoOy)0.04/γ-Al2O3 exhibited the highest activity and stable recyclability in the selective oxidation of tetralin using oxygen as the oxidant with a tetralin conversion of 68% and α-tetralone selectivity of 75% under the optimized conditions, affording a TOF value of 6.53 h−1, where the optimal reaction temperature is 120 °C and the reaction time is 8 h.

Double Mannich bases obtained from α-indanone and α-tetralone contain a bis-β-amino ketone fragment and are promising intermediate compounds for the synthesis of nitrogen heterocycles via reactions with dimethyl acetylenedicarboxylate and methyl propiolate. The products of these reactions are determined by the activated acetylene structure. The reaction begins with attack of the activated acetylenic compound on the tertiary nitrogen atom of the Mannich base to give 1,3-zwitterionic intermediate. The subsequent domino reaction is driven by neutralization of the charge on the nitrogen atom through formation and/or rupture of several C–C bonds. Intramolecular attack of the negatively charged center of the 1,3-zwitterion derived from the indanone base and dimethyl acetylenedicarboxylate on the carbonyl carbon atom of the indanone fragment is followed by domino process, leading to the formation of dimethyl 2-methyl-1,2-dihydro-9H-indeno[2,1-c]-pyridine-3,4-dicarboxylate. The reaction of the same Mannich base with methyl propiolate involves 1,3-sigma-tropic rearrangement with neutralization of the positive charge on the nitrogen atom in the intermediate structure and negative charge transfer to the carbonyl oxygen atom. Next follows aldolization/crotonization with the second β-amino carbonyl fragment to produce methyl 2′-methyl-1-oxo-1,1′,2′,3,5′,11′-hexahydrospiro-[indene-2,6′-indeno[2,1-c]azocine]-4′-carboxylate. One more reaction direction leading to the formation of linear enamines via intramolecular proton migration from the indan fragment to the C-anionic center in the 1,3-zwitterion with simultaneous elimination of 2-methylideneindan-1-one has been revealed by HPLC/MS analysis of both reaction mixtures. Such enamines, methyl 3-{methyl[(1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]amino}prop-2-enoate and dimethyl (2Z)-2-{methyl[(1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)-methyl]amino}but-2-enedioate, were isolated in the reactions of activated acetylenic compounds with the Mannich base derived from tetralone. Previously described synthesis of 1-azabicyclo[3.3.1]nonanes from Mannich bases has been reproduced, and detailed analysis of the reaction mixtures has revealed products resulting from elimination of one alkylaryl group from the zwitterionic intermediate. The formation of linear enamines, dimethyl (2Z)-2-[methyl(3-oxo-3-phenylpropyl)amino]but-2-enedioate and dimethyl (2Z)-2-{methyl-[3-oxo-3-(thiophen-2-yl)propyl]amino}but-2-enediate, suggests facile retro-aldol reaction of 3-aroyl-4-aryl-1-methylpiperidin-4-ols as the necessary step. PASS online predicted diverse biological activities of all newly synthesized compounds with a probability of 65–80%.

1,3-Diketones with quaternary stereocenters are extraordinarily useful building blocks both in academic research and industrial production. However, the access to enantiopure acyclic 2,2-disubstituted 1,3-diketones has suffered from an extremely limited substrate scope and poor stereoselectivity control. In this paper, we report the successful organocatalytic kinetic resolution of 1,3-diketones with central quaternary stereocenters through the introduction of internal nucleophiles. Two basic resolution modes were established, allowing access to a broad scope of enantioenriched 1,3-diketones with quaternary stereocenters, together with a large variety of tetralone derivatives with vicinal fully substituted carbon centers, and both of them are not easily available via currently known methods. The inherent principles between the different combinations of ketone groups and the resolution patterns were also disclosed. This work constitutes a good complementary choice for the construction of 1,3-diketones with quaternary stereogenic centers and provides insightful information for further studies on diketone substrate-mediated intramolecular annulations and kinetic resolutions.

Here, we report a formal synthesis of the marine cytotoxic meroterpenoid actinoranone. Key steps include a semipinacol rearrangement/Wittig reaction sequence and a chiral pool approach for the syntheses of the tetralone and the ocatalin fragments, respectively. The presented route provides access to the natural product in 14 steps in the longest linear sequence.

International audience; The C-H functionalization of benzo-fused cycloalkanones represents a synthetic challenge since such scaffolds display different activation sites, at sp 2 and sp 3 carbons, a bicyclic structure and various sizes of the cycloalkanone ring. Anticipating the outcome of C-H functionalization and the impact of the presence and size of the cycloalkanone ring would help to foresee synthetic routes to more complex molecular architectures. The mechanism of C-H arylation was studied using DFT calculations for tetralone, benzosuberone and indanone and compared to acetophenone. Comparison of energetic profiles allowed identifying key steps of the process. Analysis of the topology of key intermediates allowed correlating the deformation of palladacycles to the potential reactivity of the benzo-fused cycloalkanone family members. The experimental results were in full agreement with the trend provided by the theoretical study. A wide panel of diversely substituted benzo-fused cycloalkanones has been successfully obtained using optimized conditions. Moreover, an approach towards polycyclic molecules has been illustrated featuring a C-H arylation and a second step taking advantage of the remaining ketone fragment and its ability to undergo diverse transformations leading to alternative pathways to more complex molecular architectures

A novel, expedient and effective methodology for the synthesis of distinctly substituted 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline systems has been developed with a new synthetic platform. This process includes ammonium acetate-mediated cyclocondensation reactions of 3-oxo-2-arylhydrazonopropanals with benzosuberone and tetralone precursors, respectively, using the high-pressure Q-tube reactor, which has been found to be superior to both conventional heating and microwave irradiation. The novel protocol benefits from its high atom efficiency, economy, ease of workup, broad substrate scope and is also applicable to gram-scale synthesis. To identify and confirm the newly synthesized targeted compounds, the X-ray single-crystal as well as all possible spectroscopic methods were utilized. The cytotoxicity of the newly synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a–j and 5,6-dihydrobenzo-[h]quinolines derivatives 6a–e were preliminary examined toward three cell lines of human cancer; lung cancer (A549), breast cancer (MCF-7) and colon cancer (HCT-116), by applying the MTT colorimetric assay. The achieved results reflected the promising profile of the prepared compounds in this study against cancer cells and have shown that members from the synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a–j exhibited promising cytotoxicity’s against MCF-7, and A549 cancer cells respectively, while the HCT-116 (colon) cancer cells were inhibited by certain examples of 5,6-dihydrobenzo[h]quinoline derivatives 6c,d. These promising results could serve as a good primary base for further research into the design of anticancer drugs.

The compound 4-hydroxy-α-tetralone (1) is major bioactive secondary metabolite of genus Ammannia (Family- Lythraceae). The compound 1 and its various derivatives are reported to possess anti-tubercular, anti-diabetic, anti-leishmanial and bioenhancing activities. A quantitative structure activity relationship (QSAR) model for predicting anti-inflammatory activity of 4-hydroxy-α-tetralone derivatives against the tumour necrosis factor (TNF)-α, a pro-inflammatory cytokine was developed by non-linear model using artificial neural network (ANN). The regression coefficient (r2) and the leave-one-out cross-validation regression coefficient (LOO rCV2) of the QSAR model were 0.6976 and 0.4016, respectively, while the regression coefficient (r2) for the external set of experimental compounds was 0.835. The 4-hydroxy-α-tetralone virtual derivatives, which showed significant inhibition of TNF-α were subjected to docking and in-silico absorption, distribution, metabolism and excretion (ADME) studies and the results showed similar binding affinity and bioavailability in compliance with the standard drug, Diclofenac. Finally, in order to validate the developed QSAR model, the most and least active virtual derivatives were semi-synthesized, characterized on the basis of their 1H and 13C NMR spectroscopic data and in vitro tested for concentration dependent inhibition of TNF-α. The experimental results obtained, agreed well with the predicted values.

Here we present the crystal structure of SARS-CoV-2 main protease (Mpro) covalently bound to 2-methyl-1-tetralone. This complex was obtained by co-crystallization of Mpro with HEAT (2-(((4-hydroxyphenethyl)amino)methyl)-3,4-dihydronaphthalen-1(2H)-one) in the framework of a large X-ray crystallographic screening project of Mpro against a drug repurposing library, consisting of 5632 approved drugs or compounds in clinical phase trials. Further investigations showed that HEAT is cleaved by Mpro in an E1cB-like reaction mechanism into 2-methylene-1-tetralone and tyramine. The catalytic Cys145 subsequently binds covalently in a Michael addition to the methylene carbon atom of 2-methylene-1-tetralone. According to this postulated model HEAT is acting in a pro-drug-like fashion. It is metabolized by Mpro, followed by covalent binding of one metabolite to the active site. The structure of the covalent adduct elucidated in this study opens up a new path for developing non-peptidic inhibitors.

Adenosine A1 and/or A2A receptor antagonists hold promise for the potential treatment of neurological conditions, such as Parkinson’s disease. Herein, a total of seventeen benzocycloalkanone derivatives were synthesised and evaluated for affinity towards adenosine receptors (A1 and A2A AR). The obtained results allowed for the conclusion that affinity and/or selectivity of the 2-benzylidene-1-indanone and -tetralone derivatives toward A1 and/or A2A ARs may be modulated by the nature of the substituents (either -OH, -OCH3 or morpholine) attached at position C4 of the 1-indanone core and C5 of the 1-tetralone core as well as the meta (C3’) and/or para (C4’) position(s) on ring B. Several compounds (2a–b, 3b–c and 4a–b) possessed affinity for the A1 and/or A2A AR below 10 µM. Additionally, compounds 2a, 3b and 4a were A1 AR antagonists. These results, once again, confirmed the importance of C4 methoxy-group substitution on ring A in combination with meta (C3’) and/or para (C4’) hydroxyl-group substitution ring B of the 2-benzylidene-1-indanone scaffold leading to drug-like compounds 1h and 1j with affinity in the nanomolar-range.

Seventeen novel 2-(5-amino-1-(substituted sulfonyl)-1H-1,2,4-triazol-3-ylthio)-6- isopropyl-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one compounds were synthesized from the abundant and naturally renewable longifolene and their structures were confirmed by FT-IR, NMR, and ESI-MS. The in vitro cytotoxicity of the synthesized compounds was evaluated by standard MTT assay against five human cancer cell lines, i.e., T-24, MCF-7, HepG2, A549, and HT-29. As a result, compounds 6d, 6g, and 6h exhibited better and more broad-spectrum anticancer activity against almost all the tested cancer cell lines than that of the positive control, 5-FU. Some intriguing structure&ndash, activity relationships were found and are discussed herein by theoretical calculation.

In our previous work, spiroxatrine was taken as reference compound to develop selective NOP ligands. Therefore, several triazaspirodecanone derivatives were synthesized. Here, we verify their selectivity towards other 5-HT1 receptor subtypes and with respect to α2-AR (Adrenergic Receptors). Binding affinities were determined on cells expressing human cloned receptors for 5-HT1A/B/D and α2A/B/C subtypes. The Ki values were determined for those with at least 50% radioligand inhibition. All our derivatives show a moderate affinity for α2 subtypes, spanning from 5 to 7.5 pKi values. Moreover, they show affinity values in a μM–nM range at the 5-HT1A receptor, while they are practically inactive at 5-HT1B and 5-HT1D subtypes. Compound 11, the best of the series, has a 5-HT1A pKi value of 8.43 similar to spiroxatrine but, notably, it has a 5-HT1A favorable selectivity ratio of 52, 8 and 29, respectively over α2A, α2B and α2C adrenoceptor subtypes. In this SAR study, a 5-HT1A selective ligand has been identified in which a tetralone moiety replaced the 1,4-benzodioxane of spiroxatrine and the methylene linker to the triazaspirodecanone portion was maintained in position 2.

A racemic spirohydantoin derivative with two aromatic substituents, a tetralin and a 4-methoxybenzyl unit, was synthesized and its crystal structure was determined. To define the relationship between molecular stereochemistry and spatial association modes, development of the crystal packing was analyzed through cooperativity of intermolecular interactions. Homo and heterochiral dimeric motifs were stabilized by intermolecular N−H⋅⋅⋅O, C−H⋅⋅⋅O, C−H⋅⋅⋅π interactions and parallel interactions at large offsets (PILO), thus forming alternating double layers. The greatest contribution to the total stabilization came from a motif of opposite enantiomers linked by N−H⋅⋅⋅O bonds (interaction energy=−13.72 kcal/mol), followed by a homochiral motif where the 4-methoxybenzyl units allowed C−H⋅⋅⋅π, C−H⋅⋅⋅O interactions and PILO (interaction energy=−11.56 kcal/mol). The number of the contact fragments in the environment of the tetralin unit was larger, but the 4-methoxybenzyl unit had greater contribution to the total stabilization. The statistical analysis of the data from the Cambridge Structural Database (CSD) showed that this is a general trend. The compound is a potential inhibitor of kinase enzymes and antigen protein-coupled receptors. A correlation between the docking study and the results of the CSD analysis can be drawn. Due to a greater flexibility, the 4-methoxybenzyl unit is more adaptable for interactions with the biological targets than the tetralin unit. This is the peer-reviewed version of the article: Anita M. Lazić, Ivana S. Đorđević, Lidija D. Radovanović, Dragan M. Popović, Jelena R. Rogan, Goran V. Janjić, Nemanja P. Trišović, Self-Assembly and Biorecognition of a Spirohydantoin derived from α-Tetralone: Interplay between Chirality and Intermolecular Interactions, ChemPlusChem, 2020, 85, 6, 1220-1232, doi: [https://doi.org/10.1002/cplu.202000273] The published version: [https://cer.ihtm.bg.ac.rs/handle/123456789/3638]

Made available in DSpace on 2022-04-29T08:36:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-15 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The halido-α-bridge cleavage reactions between [Pd(C2,N-tetrox)(μ-Cl)]2 precursor (tetrox = E-α-tetralone oxime) with phosphines, in 1:2 molar ratio, have afforded mononuclear cyclopalladated compounds of the type [PdCl(C2,N-tetrox)(L)] {L = triphenylphosphine (1); tris(4-methylphenyl)phosphine (2); tris(4-fluorophenyl)phosphine (3) and tris(4-methoxyphenyl)phosphine (4)}. The compounds have been characterized by elemental analyses, infrared (FT-IR) and 1H, 13C{1H} and 31P{1H}-NMR spectroscopies. The molecular structure of 3 has been determined by single crystal X-ray diffraction (SC-XRD) and the Hirshfeld Surface calculation (HS) has been performed. The antiproliferative activity of compounds 1–4 has been evaluated against breast (MCF-7) and lung (A549) human cancer cells, and human lung fibroblast (MRC-5). All cyclopalladated compounds have been more active than cisplatin against MCF-7 cells, with IC50 values ranging from 19 to 26 µM. Binding experiments involving compound 3 with ct-DNA and human serum albumin (HSA) have been carried out using spectroscopic techniques. The interaction between compound 3 and HSA has been studied by means of molecular docking. UNESP – Univ Estadual Paulista Institute of Chemistry Department of Analytical Physical Chemistry and Inorganic Chemistry UEL – Univ Estadual de Londrina Departamento de Química USP – Univ de São Paulo Instituto de Física de São Carlos UFS – Univ Federal de Sergipe Departamento de Química UNESP – Univ Estadual Paulista Institute of Chemistry Department of Analytical Physical Chemistry and Inorganic Chemistry FAPESP: 2012/15486–3 FAPESP: 2016/17711­5 FAPESP: 422105/2016–3 FAPESP: 475322/2009–6

Background Chalcone has been identified as a promising lead for the design of Monoamine Oxidase (MAO) inhibitors. This study attempted to discover potent and selective chalcone-derived MAO inhibitors by synthesising a series consisting of various cyclic chalcone derivatives. The cyclic chalcones were selected based on the possibility that their restricted structures would confer a higher degree of MAO isoform selectivity, and included the following chemical classes: 1-indanone, 1- tetralone, 1-benzosuberone, chromone, thiochromone, 4-chromanone and 4-thiochromanone. Methods The cyclic chalcone derivatives were synthesised via a one-pot Claisen-Schmidt condensation reaction. The MAO inhibitory properties of the chalcone derivatives were evaluated with the recombinant human MAO-A and MAO-B enzymes and the potencies were expressed as the IC50 values. A selected inhibitor was docked into an active site model of MAO-B. Results The results showed that the cyclic chalcones are in general good potency, and in most instances specific inhibitors of the MAO-B isoform. Among these compounds, the 4-chromanone derivative was the most potent MAO-B inhibitor with an IC50 value of 0.156 µM. To further investigate the MAO inhibition of cyclic chalcones, a series of twenty-three 2-benzylidene-1-tetralone derivatives were synthesised and evaluated as MAO inhibitors. Most 2-benzylidene-1-tetralones possess good inhibitory activity and specificity for MAO-B with the most potent inhibitor displaying an IC50 value of 0.0064 µM, while the most potent MAO-A inhibitor possessed an IC50 value of 0.754 µM. Conclusion This study thus shows that certain cyclic chalcones are human MAO-B inhibitors, compounds that could be suitable for the treatment of neurodegenerative disorders such as Parkinson's disease.

We have elaborated a two-step catalytic approach to nafoxidine, a key precursor to lasofoxifene. Firstly, an efficient α-arylation of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one with chlorobenzene was developed, which operates at low 0.1 mol% Pd-132 catalyst loading in the presence of 1.9 equivalents of sodium tert-butoxide at 60 °C in 1,4-dioxane and provides 6-methoxy-2-phenyl-3,4-dihydronaphthalen-1(2H)-one in 90% yield. Secondly, we have demonstrated that 6-methoxy-2-phenyl-3,4-dihydronaphthalen-1(2H)-one can be converted to nafoxidine in 61% yield via CeCl3 promoted reaction with (4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)lithium, which is formed in-situ from the corresponding arylbromide precursor and n-butyllithium. Altogether, the shortest two-step approach to nafoxidine from simple tetralone commodity starting material has been developed with overall 55% yield. The developed synthetic approach to nafoxidine has several beneficial aspects over the one used in the synthetic route primarily developed for the preparation of lasofoxifene.

Ginger root, strawberry tree and mandarin growing in Algeria were evaluated for their ability to stereoselective reduction of prochiral ketones. The reactivity and the enantioselectivity are strongly dependent on the biocatalyst used, and the structure of ketone. High enantioselectivities were observed for some substrates (70–99% ee) especially for the bioreduction of acetophenone 1, p-chloroacetophenone 2, tetralone 5, thiochromanone 6 and chromanone 7. Using two different batchs of Citrus reticulata from two regions of our country Annaba and Skikda, the corresponding optically active alcohols were obtained with high enantioselectivity and Skikda's variety was the best biocatalyst. The results reveal that these plants species can be a promising biocatalysts for the production of key intermediates.

Bioinspired manganese complexes have emerged as attractive catalysts for a number of selective oxidation reactions over the past several decades. In the present study, we report the enantioselective oxidation of spirocyclic compounds with manganese complexes bearing tetradentate N4 ligands as catalysts and aqueous H2O2 as a terminal oxidant under mild conditions; spirocyclic tetralone (1a) and its derivatives bearing electron-donating and -withdrawing substituents are converted to their corresponding chiral spirocyclic β,β′-diketones with high yields and enantioselectivities. Spirocyclic indanones are also converted to the β,β′-spirobiindanones with high enantioselectivities. Indeed, the reaction expands the diversity of chiral spirocyclic diketones via a late-stage oxidative process. In addition, it is of importance to note that the catalytic reaction can be easily scaled up and the chiral spirocyclic β,β′-diketones can be transformed into diol products. In mechanistic studies, we have shown that (1) ket...

International audience; As an extension of our previous work on donepezil-based “bio-oxidizable” prodrug approach, two new classes of N-benzylpyridinium donepezil analogues in tetralone B2 and acetophenone B3 series and a new set of indanone derivatives B1 were investigated along with the corresponding dihydropyridine prodrugs A1-3. A total of fifty one N-benzylpyridinium quaternary donepezil analogues B1-3 and twenty two prodrugs A1-3 were synthesized and evaluated for their inhibitory activities against hAChE and eqBuChE. While most prodrugs A1-3 were demonstrated to be inactive against AChE (IC50 > 10 μM), a large number of the corresponding N-benzylpyridinium salt B1-3 exhibited appealing three-to-one-digit nanomolar hAChE inhibitory activities and even reaching subnanomolar activity (IC50 = 0.36 nM). In addition, in silico docking studies were conducted for several compounds to explain the more relevant in vitro results. Lastly, the influence of the two stereogenic centers in prodrugs A was also evaluated, highlighting not only marked differences in residual AChE inhibitory activity of the four separated isomers of prodrug 23h (IC50 ranging from 173 nM to 10 μM) but also significant variations of the oxidation rate between two separated diastereoisomers of prodrug 24a. This work provides useful information in the search of a preclinical candidate to conduct further development of this attractive “bio-oxidizable” prodrug strategy.

Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) plays an important role in triglyceride synthesis and is a target of interest for the treatment of metabolic disorders. Herein we describe the structure–activity relationship of a novel tetralone series of DGAT1 inhibitors and our strategies for overcoming genotoxic liability of the anilines embedded in the chemical structures, leading to the discovery of a candidate compound, (S)-2-(6-(5-(3-(3,4-difluorophenyl)ureido)pyrazin-2-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid (GSK2973980A, 26d). Compound 26d is a potent and selective DGAT1 inhibitor with excellent DMPK profiles and in vivo efficacy in a postprandial lipid excursion model in mice. Based on the overall biological and developability profiles and acceptable safety profiles in the 7-day toxicity studies in rats and dogs, compound 26d was selected as a candidate compound for further development in the treatment of metabolic disorders.

Total synthesis and structural determination of XR774 has been accomplished. The benzo[ j]fluoranthene skeleton has been constructed by regioselective coupling between tetraline 3 and tetralone 4 successively followed by the sequential transformation including the Birch reduction to prepare allylic alcohol, simultaneous bromination of vinylic and aromatic moieties, and the nickel-mediated intramolecular coupling reaction. The optical resolution of racemic 17 led to the first total synthesis of (-)-XR774.

The chemosynthesis and potential as green herbicides of 4,8-dihydroxy-1-tetralone (4, 8-DHT) and its derivates were emphatically addressed in this study. Firstly, the synthesis of 4, 8-DHT from commercially available material 1, 5-dihydroxynaphthalene was carried out through a novel route of five reaction steps. Then, its five derivates including 4-benzoyl-8-hydroxy-1-tetralone, 4-(3-hydroxypropoxy)- 8-hydroxy-1- tetralone, 4-(2,3-dihydroxypropoxy)-8-hydroxy-1-tetralone, 4-hydroxy-8-(3-hydroxy propoxy) −1-tetralone and 4-hydroxy-8-(2,3-dihydroxypropoxy)-1- tetralone were prepared by modifying alcoholic and phenolic hydroxyl in C-4 and C-8 position of 4,8-DHT molecular structure. After that, these synthesized compounds were examined for their toxicity against six kinds of weeds (Lolium perenne, Phalaris arundinacea, Elymus dahuricus, Cichorium intybus, Sorghum sudanense, and Trifolium repens) in vitro. In general, high concentration could generally inhibit while low concentration might promote the growth of weeds. Among these compounds, 4-(3-hydroxypropoxy)-8 −hydroxy-1-tetralone and 4-hydroxy-8- (3-hydroxypropoxy) −1-tetralone showed significant phytotoxic activities against the six tested weeds, while 4-hydroxy-8-(2,3-dihydroxypropoxy) −1-tetralone was less toxic. For all the six tested weeds, E. dahuricus appeared the most sensitive to the treatments of 4, 8-DHT compounds. Hence, it has been suggested that variables including compound type and concentration as well as weed species should be seriously considered in order to develop and utilize the group of 4, 8-DHT compounds as herbicide in future.

A route to compounds with a 5,7-diazapentacene skeleton has been established involving a Friedländer reaction. A diaminodiketone 8 has been made by a novel method and reacted with cyclohexanone to prepare an octa-hydro-5,7-diazapentacene 7a and with tetralone to produce a dibenzotetrahydro-5,7-diazapentacene 7b. Reaction of the diaminodiketone with a diarylethanone followed by oxidation gave a tetrabenzo-5,7-diazapentacene 18b. Compound 7b undergoes solid-state dimerization during single-crystal X-ray analysis. These materials possess lower frontier orbitals than pentacene and show strong absorption and fluorescence which is affected by the presence of acid. In particular 18b shows a remarkable colour change in solution upon addition of acid. These results suggest that suitably functionalised 5,7-diazapentacenes could be promising candidates for optoelectronic applications. MOE (Min. of Education, S’pore) Accepted version