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Introduction: Juglans regia Linn. and Carya illinoinensis (Wangenh.) K. Koch are nut‐producing plant species of the Juglandaceae family. Bioactive compounds like naphthoquinones, tetralones, and diarylheptanoids are dominant in these species. Objective: The study aimed to develop and validate a fast and sensitive analytical method by ultrahigh‐performance liquid chromatography diode array detection mass spectrometry (UHPLC‐DAD‐MS) for quantification and identification of bioactive compounds in fruit pericarps and leaves of J. regia and C. illinoinensis collected from two different states of north India. Methodology: The dried pericarps of J. regia and C. illinoinensis (500 mg) were extracted with ethyl acetate–methanol (50:50 v/v, 20 mL, 50°C, 30 min) by ultrasonication and analysed by ultrahigh‐performance liquid chromatography diode array detection quadrupole time‐of‐flight tandem mass spectrometry (UHPLC‐DAD‐QTOF‐MS/MS) for qualitative and quantitative examination of phytoconstituents. The method was validated according to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human use (ICH) guidelines for linearity, precision, accuracy, limit of detection (LOD), and limit of quantification (LOQ). Results: Here, we report the quantification of dihydrophaseic acid (1), 4,5‐dihydroxytetralone (2), 4,8‐dihydroxytetralone (3), 5,8‐dihydroxy‐3‐methoxytetralone (4), and juglanin A (5) in the pericarps and leaves of J. regia and C. illinoinensis. Furthermore, using the hyphenated analytical method, a total of 62 compounds were tentatively characterised in different samples. The principal component analysis (PCA) showed diversity between the analysed sample's composition. Also, the study evaluated the variation of bioactive compounds among different parts of J. regia and C. illinoinensis collected from different regions of northern India by UHPLC‐DAD‐QTOF‐MS/MS. Conclusion: The developed method is simple, rapid, and selective for the identification and characterisation of bioactive molecules. A rapid UHPLC‐DAD method was developed and validated for the quantification of five compounds in fruit pericarps and leaves samples of J. regia and C. illinoinensis. A total of 62 compounds were tentatively characterized in samples collected from different locations using UHPLC‐DAD‐QTOF‐MS/MS. [ABSTRACT FROM AUTHOR]

Natural allylpolyalkoxybenzenes were used to synthesize polyalkoxychalcones featuring various conformations, including β-methyl-substituted S-trans-conformers and tetralone derivatives with restricted S-cis conformation. Antiproliferative antitubulin activity and cyto-toxicity of these compounds were studied using a sea urchin embryo model and human cancer cell lines. S-trans-Restricted chalcone 3y was found to exhibit high activity in the inhibition of cancer cell growth by microtubule destabilization with IC50 = 0.02–0.04 µmol L−1. [ABSTRACT FROM AUTHOR]

The efficient RuPHOX–Ru catalyzed asymmetric hydrogenation of α-substituted tetralones via a dynamic kinetic resolution has been achieved for the synthesis of chiral tetrahydronaphthols. The mechanism study indicated that hydrogenation with H2 gas, rather than transfer hydrogenation with EtOH solvent as the hydrogen source, predominates in the reaction pathway. [ABSTRACT FROM AUTHOR]

Two undescribed diarylheptanoids, 3-(R)-acetyl-1-(3′,4′-dihydroxyphenyl)-7-(4′′-hydroxy-3′′ -methoxyphenyl)-heptane (1) and 11-Hydroxy-1,17-epoxy-7-(2-hydroxylphenyl)-13-(16-methoxyphenyl)-heptane (2) together with known compounds, namely, 11-Oxo-1,17-epoxy-7-(2-hydroxylphenyl)-13-(16-methoxyphenyl)-heptane (3) 3,4,5-Trihydroxytetralone (4) 4,8- Dihydroxytetralone (5), 4,5-Dihydroxytetralone (6), 5,8-Dihydroxy-3-methoxytetralone (7) were isolated from ethyl acetate extract of the green husk of Carya illinoinensis. The structures of compounds were established on the basis of IR, 1H NMR, 13C NMR, DEPT, HSQC, HMBC, COSY spectroscopic and ESI-MS analysis. The isolated compounds were evaluated for AChE (acetylcholinesterase inhibition) and observed that compound 5 was potent inhibitor with IC50 of 101.48 ± 4.00 µg/mL. [ABSTRACT FROM AUTHOR]

One new tetralone derivative, named aladothalen (1), and one known biogenetically related compound, (3S,4S)-3,4,8-trihydroxy-3,4-dihydronaphthalen-1(2 hours)-one (2), were isolated from a deep-sea-derived-fungal Cladosporium sp. HDN17-58. Their structures, including absolute configurations, were elucidated by extensive NMR, MS, and ECD analyses. Compound 1 exhibited potent bacteriostatic activity against Bacillus cereus, Mycobacterium phlei and methicillin-resistant coagulase-negative Staphylococci, with a MIC value of 25 µM. [ABSTRACT FROM AUTHOR]

In the actinorhodin type II polyketide synthase, the first polyketide modification is a regiospecific C9-carbonyl reduction, catalyzed by the ketoreductase (actKR). Our previous studies identified the actKR 94-PGG-96 motif as a determinant of stereospecificity. The molecular basis for reduction regiospecificity is, however, not well understood. In this study, we examined the activities of 20 actKR mutants through a combination of kinetic studies, PKS reconstitution, and structural analyses. Residues have been identified that are necessary for substrate interaction, and these observations have suggested a structural model for this reaction. Polyketides dock at the KR surface and are steered into the enzyme pocket where C7-C12 cyclization is mediated by the KR before C9-ketoreduction can occur. These molecular features can potentially serve as engineering targets for the biosynthesis of novel, reduced polyketides.

A mild electrochemical method for the regioselective preparation of 1‐tetralones under environmentally friendly conditions from readily available cyclobutanols was developed. A series of aromatic‐ and heteroaromatic‐fused 1‐tetralones was accessed through ring expansion of the functionalized cyclobutanols via electrochemical generation of alkoxy radicals and intramolecular cyclization. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a highly malignant brain tumour characterised by limited treatment options and poor prognosis. The tumour microenvironment, particularly the central hypoxic region of the tumour, is known to play a pivotal role in GBM progression. Cells within this region adapt to hypoxia by stabilising transcription factor HIF1-α, which promotes cell proliferation, dedifferentiation and chemoresistance. In this study we sought to examine the effects of NNC-55-0396, a tetralol compound which overactivates the unfolded protein response inducing apoptosis, using the organ-on-chip technology. We identified an increased sensitivity of the hypoxic core of the chip to NNC, which correlates with decreasing levels of HIF1-α in vitro. Moreover, NNC blocks the macroautophagic process that is unleashed by hypoxia as revealed by increased levels of autophagosomal constituent LC3-II and autophagy chaperone p62/SQSTM1. The specific effects of NNC in the hypoxic microenvironment unveil additional anti-cancer abilities of this compound and further support investigations on its use in combined therapies against GBM., (© 2024. The Author(s).)

The emergence of new synthetic cathinones continues to be a matter of public health concern. In fact, already known products (drugs) are being rapidly replaced by new structurally related alternatives, whereby modifications in the basic cathinone structure are used by manufacturers to circumvent the legislation. On the other hand, some derivatives of synthetic cathinones represent important pharmaceuticals with antidepressant properties. In the search for pharmaceutically relevant analogs, the main goal of the present study was to design and characterize novel cyclic α-tetralone-based derivatives of synthetic cathinones. We synthesized a series of derivatives and verified their chemical structure. Subsequently, chiral separation has been accomplished by high-performance liquid chromatography (HPLC) equipped with a circular dichroism (CD) detector, which directly provided CD spectra of the enantiomers of the analyzed substances at 252 nm. Using density functional theory calculations, we have obtained stable conformers of selected enantiomers in solution and their relative abundances, which we used to simulate their spectra. The experimental and calculated data have been used to assign the absolute configuration of six as-yet unknown synthetic cathinones., (© 2024 The Authors. Chirality published by Wiley Periodicals LLC.)

Juglonols A−C (1−3), three new juglone derivatives possessing a hydroxyethyl side chain, were isolated from an organic extract of the immature exocarps of Juglans mandshurica together with five known tetralones (4–8). Their structures were elucidated by extensive spectroscopic analyses and comparison with literature data. The new juglone derivatives exhibited inhibitory activities towards a panel of bacteria and fungi, as well as cancer cell lines. In contrast, the known tetralone homologues (4−8) appeared to be much less efficacy. [ABSTRACT FROM AUTHOR]

An iodine‐promoted regioselective sulfenylation/deoxygenation/aromatization reaction of 1‐tetralones with disulfides has been developed. This process could be modified to synthesize 2‐naphthyl thioethers and 1‐naphthyl thioethers in moderate to excellent yields, respectively. Furthermore, when the reaction was extended to 2‐tetralones, 2‐naphthyl thioethers were obtained as the sole products. The current study bridges the deoxygenation and sulfenylation/aromatization of ketones, thus providing a new tool in organic synthesis. [ABSTRACT FROM AUTHOR]

In the traditional Bamford‐Stevens‐Shapiro‐type reaction, electrophiles replace the carbonyl group to synthesize polysubstituted carbon‐carbon double bonds. We herein report an unusually simple and general procedure to access carbon‐carbon double bonds from ketones and install electrophiles at the original α‐position of the carbonyl functional group, thus providing a new tool in organic synthesis. This reaction shows a wide substrate scope and functional‐group tolerance. Nice and easy: An unusually simple and general procedure to access carbon‐carbon double bonds from ketones is described. Electrophiles are installed at the original α‐position of the carbonyl functional group, thus providing a new tool in organic synthesis. [ABSTRACT FROM AUTHOR]

Graphical abstract To create your abstract, type over the instructions in the template box below. Fonts or abstract dimensions should not be changed or altered. Abstract The enantioselective electrophilic fluorination of α-aryl-tetralones is promoted by cinchonine/selectfluor combinations. This strategy allows a facile synthesis of the corresponding 2-fluoro-2-aryl-1-tetralones with excellent yields (up to >98%) and moderate to good enantioselectivity (up to74%). [ABSTRACT FROM AUTHOR]

Abstract 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. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Graphical abstract A green approach for the synthesis of 1-tetralones and fluorenones in presence of resorcin[4]arene as reusable and effective catalyst in aqueous medium from the readily available starting materials. Abstract An efficient, straightforward and environmentally benign process has been developed for the synthesis of fluorenone and 1-tetralone derivatives using cyclic 1,3 -dione, malononitrile and dialkylacetylenedicarboxylate as starting materials in aqueous medium. The reaction is favoured in presence of resorcin[4]arene which is effective as a reusable organocatalyst. The catalyst has been easily synthesized and characterized by 1H, 13C NMR, IR, XRD and HRMS analyses. Resorcin[4]arene afforded the resulted products in a shorter time and in good yields. The recyclability of the catalyst was established up to 6th cycle by FT-IR and SEM images. [ABSTRACT FROM AUTHOR]

A metal-free, ultrasound-assisted approach for the synthesis of highly functionalized 2-tetralones in high yields is described. The process involves ring transformation of 2H-pyran-2-ones with the spirocyclic ketone 1,4-cyclohexandione monoethylene ketal to yield spirocyclic ketals and subsequent acid-mediated hydrolysis. This protocol is free from any organometallic reagents, is economical and tolerates a wide range of functional groups. [ABSTRACT FROM AUTHOR]

A two-steps synthesis of thiazolidin-4-ones, from α-tetralone 6 or thiochroman-4-one 7, catalyzed by acids is described. The reactions of α-tetralone 6 or thiochroman-4-one 7, with substituted thiosemicarbazides, under AcOH or heteropolyacid (HPAs) catalysis afford thiosemicarbazones 8 and 9 in excellent yields. Condensations of the previous compounds 8 and 9 with α-bromoester, under sulfuric acid or heteropolyacid catalysis, yield the corresponding thiazolidin-4-ones 10 and 11. [ABSTRACT FROM AUTHOR]

1-Arylidene-2-tetralone (2), obtained from condensation of 2-tetralone and aromatic aldehydes in acetic acid and HCl, on condensation with thiosemicarbazide in acidic and alkaline medium afforded tetrahydro-2 H -benzo[ e ]indazole-2-carbothioamide as trans (3) and cis (4) diastereoisomers of 1- H and 9b- H respectively. The synthesis of new indazolyl-thiazol-4(5 H )-ones (5) from trans isomer (3) and α-halo acids is reported. A DFT study along with single crystal X-ray diffraction data of a representative compound (5a) is presented. The chemistry of the reaction of indazole-2-carbothioamides with methyl iodide, DMAD and acetic anhydride is described. Eight newly synthesised compounds were screened for their antibacterial and antifungal activities. Some of the compounds have shown promising antimicrobial activities. [ABSTRACT FROM AUTHOR]

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(2 H )-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(2 H )-one in 90% yield. Secondly, we have demonstrated that 6-methoxy-2-phenyl-3,4-dihydronaphthalen-1(2 H )-one can be converted to nafoxidine in 61% yield via CeCl 3 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. [ABSTRACT FROM AUTHOR]

Abstract: A new protocol for the synthesis of chiral β‐aminotetralins has been developed via chiral phosphoric acid‐catalyzed asymmetric reductive amination of β‐tetralones using a Hantzsch ester as an organic hydride donor. Various chiral β‐aminotetralins were obtained in good yields with good to high enantioselectivities. Furthermore, the utility of our new protocol was successfully demonstrated in the enantioselective synthesis of rotigotine. [ABSTRACT FROM AUTHOR]

One-pot three-component Beginelli-like reactions of a ketone 1, an aryl aldehyde 2, and thiourea 3 in the presence of sodium hydroxide are described. In this reaction, 3,4,5,6-tertrahydro-4-substituted quinazoline-2(1H)-thione derivatives 4a–h were obtained in good yields (73–85%). The compound 4a has been characterized by single crystal X-ray analysis. All the synthesized compounds 4a–h and 5a–b were screened for their in vitro antioxidant activity. Compounds 4c, 4e, and 4h have exhibited an excellent than the standard ascorbic acid. Compounds 4d, 4f, and 4g have also shown good activity. Remaining compounds show moderate antioxidant activity. [ABSTRACT FROM AUTHOR]

Antagonists of the adenosine receptors (A1 and A2A) are thought to be beneficial in neurological disorders, such as Alzheimer's and Parkinson's disease. The aim of this study was to explore 2-benzylidene-1-tetralone derivatives as antagonists of A1 and/or A2A adenosine receptors. In general, the test compounds were found to be selective for the A1 adenosine receptor, with only three test compounds possessing affinity for both the A1 and A2A adenosine receptor. The 2-benzylidene-1-tetralones bearing a hydroxyl substituent at either position C5, C6 or C7 of ring A displayed favourable adenosine A1 receptor binding, while C5 hydroxy substitution led to favourable A2A adenosine receptor affinity. Interestingly, para-hydroxy substitution on ring B in combination with ring A bearing a hydroxy at position C6 or C7 provided the 2-benzylidene-1-tetralones with both A1 and A2A adenosine receptor affinity. Compounds 4 and 8 displayed the highest A1 and A2A adenosine receptor affinity with values below 7 μ m. Both these compounds behaved as A1 adenosine receptor antagonists in the performed GTP shift assays. In conclusion, the 2-benzylidene-1-tetralone derivatives can be considered as lead compounds to design a new class of dual acting adenosine A1/A2A receptor antagonists that may have potential in treating both dementia and locomotor deficits in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Mesoporous molecular sieve SBA-16 supported Pd Ni bimetallic catalysts were synthesized by the co-impregnation method. Pd Ni/SBA-16 bimetallic Im 3m mesoporous catalyst showed superior catalytic performance in the production of jet-fuel range hydrocarbons. Vapour phase hydrodeoxygenation of α-tetralone was carried out under ambient pressure and the highest selectivity (88.21%) for the isomerized product trans -decalin was obtained. Pd Ni impregnated on different mesoporous (MCM-41, SBA-15, KIT-6) and metal oxides (γ-Al 2 O 3 , CeO 2 , TiO 2 , ZrO 2 , SiO 2 ) supports and the catalytic activity was compared with Pd Ni/SBA-16. Synergetic interaction between the Pd(111) and Ni(111) with increased total acidity enhanced the catalytic activity of Pd Ni/SBA-16. Among the bimetal, Nickel was found to be the most active metal for the complete reduction of aromatic ring, while Pd favoured the deoxygenation. The major products obtained from hydrodeoxygenation of α-tetralone were cis/trans- decalin, tetralin and α-tetralol. [ABSTRACT FROM AUTHOR]

A method has been developed for the sulfonamidation of tetralones and 1,4-naphthoquinones by using sulfonyl azides in the presence of a RuII/AgI catalytic system. In case of tetralones, C−H bond functionalization occurred exclusively at the ortho position, whereas 1,4-addition was the main transformation for 1,4-naphthoquinones. This method is highly regioselective and was successfully utilized for the synthesis of sivelestat, an inhibitor of human neutrophil elastase. [ABSTRACT FROM AUTHOR]

Herein, we demonstrate an efficient two-step preparation of substituted cyclobutyl-fused 1-tetralones bearing four contiguous stereochemical centers, including (i) intermolecular aldol condensation of o -cinnamyl acetophenones with arylaldehydes, and (ii) intramolecular photolytic annulation of the resulting o -cinnamyl chalcones. The key structures are determined by single-crystal X-ray analysis. Plausible mechanism is also presented. To create your abstract, type over the instructions in the template box below.Fonts or abstract dimensions should not be changed or altered. [Display omitted] [ABSTRACT FROM AUTHOR]

Crystal structures are reported from data collected at 100 K of (E)-2-(X-benzylidene)-1-tetralone (2: X = 3-O2N; 3: X = 4-O2N; 5: X = 4-HO; 6: X = 4-Me2N; 7: 4-NC), (E)-2-(X-benzylidene)-6-MeO-1-tetralone, 8, and (E)-2-(X-benzylidene)-5-MeO-1-tetralone 9. Also reported herein are the Hirshfeld surface calculations for these compounds as well as those of (E)-2-(X-benzylidene)- 1-tetralone (1: X = H; 4: X = 4-MeO), whose structures were previously reported. The molecules are not planar as shown by the dihedral angles of 45.66(5)-69.78(5)° between the phenyl groups and by the puckered cyclohexenyl rings. A common feature of the molecular conformations is the C-H · · · O1(carbonyl) intramolecular hydrogen bond. The carbonyl oxygen atom plays significant roles in the interactions in all compounds baring compound 8. However, there is no consistent set of intermolecular interaction in this group of compounds. Intermolecular interactions present in each compound are some of the O-H · · · O, C-H · · · A (A = O, N or π), A-O · · · π (A = C or N) and π · · · π interactions. The only compound exhibiting a classical O-H · · · O hydrogen bond is compound 5. C-H · · · π interactions are found in all compounds, and while π · · · π interactions are present in compounds 2, 3, 7 and 9, no consistent type of stacking arrangement is shown. The Hirshfeld surface calculations, while generally concurring with the intermolecular interactions indicated by PLATON analyses, also reveal short interactions, which fall below the PLATON cut-off parameters. [ABSTRACT FROM AUTHOR]

Adenosine A 1 and A 2A receptors are attracting great interest as drug targets for their role in cognitive and motor deficits, respectively. Antagonism of both these adenosine receptors may offer therapeutic benefits in complex neurological diseases, such as Alzheimer’s and Parkinson’s disease. The aim of this study was to explore the affinity and selectivity of 2-benzylidene-1-tetralone derivatives as adenosine A 1 and A 2A receptor antagonists. Several 5-hydroxy substituted 2-benzylidene-1-tetralone analogues with substituents on ring B were synthesized and assessed as antagonists of the adenosine A 1 and A 2A receptors via radioligand binding assays. The results indicated that hydroxy substitution in the meta and para position of phenyl ring B, displayed the highest selectivity and affinity for the adenosine A 1 receptor with K i values in the low micromolar range. Replacement of ring B with a 2-amino-pyrimidine moiety led to compound 12 with an increase of affinity and selectivity for the adenosine A 2A receptor. These substitution patterns led to enhanced adenosine A 1 and A 2A receptor binding affinity. The para-substituted 5-hydroxy analogue 3 behaved as an adenosine A 1 receptor antagonists in a GTP shift assay performed with rat whole brain membranes expressing adenosine A 1 receptors. In conclusion, compounds 3 and 12 , showed the best adenosine A 1 and A 2A receptor affinity respectively, and therefore represent novel adenosine receptor antagonists that may have potential with further structural modifications as drug candidates for neurological disorders. [ABSTRACT FROM AUTHOR]

Racemic trans-cyclohexane-1,2-diamine was allowed to react with eleven aldehydes with different patterns of substitution at the aromatic ring, in the absence of solvent, by manually milling the reagents. The corresponding imines were obtained in moderated to high chemical yields, in only 10 minutes of reaction. A one-pot, two-step preparation of stable complexes of selected imines with Pd(OAc)2 and Cu(OAc)2 and the use of these complexes as catalysts in the aromatization of methyl 1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate to the corresponding methyl 1-hydroxynaphthalene-2-carboxylates, is also reported. [ABSTRACT FROM AUTHOR]

We present an enantioselective synthesis of cis-fused tricyclic 1-tetralones via oxidative kinetic resolution in the presence of cumene hydroperoxide (CHP) and guanidine-bisurea bifunctional organocatalyst. This reaction affords the corresponding α-hydroxylation products together with unreacted tetralones in good to high enantioselectivity, with s values as high as 42. The reaction was successfully applied for the synthesis of the core structure of a kainoid derivative, 4-(2-methoxyphenyl)-2-carboxy-3-pyrrolidineacetic acid (MFPA). [ABSTRACT FROM AUTHOR]

Described herein is the enantioselective syntheses of (+)- and (−)-rishirilide B from the corresponding optically active β-substituted tetralones, which were obtained by oxidative kinetic resolution based on α-hydroxylation in the presence of a chiral guanidine-bisurea bifunctional organocatalyst. Benzylic oxidation of the tetralones at C1 followed by regioselective isomerization of the oxabenzonorbornadiene structure led to rishirilide B. Our findings lead to the revision of the previously proposed (2R,3R,4R) absolute configuration of (+)-rishirilide B to (2S,3S,4S). [ABSTRACT FROM AUTHOR]

This paper describes the transition metal-free indole annulation-oxidative cross-coupling of 2-nitrocinnamaldehydes or ( E)-3-(1-nitronaphthalen-2-yl)acrylaldehyde with β-tetralones for the construction of diverse 3-naphthylindole and 3-naphthylbenzo[ g]indole fluorophores in moderate to good yields. This unique annulation reaction proceeds via the domino Michael addition/hemiacetalization/intramolecular addition of an enolate to a nitro group/decarbonylation/oxidative aromatization sequence under transition metal-free conditions without the use of an external reductant and oxidant. The synthetic utility of this protocol has been also demonstrated by evaluating the photophysical properties of the synthesized 3-naphthylindole and 3-naphthylbenzo[ g]indole derivatives. [ABSTRACT FROM AUTHOR]

Ketones bearing two bulky substituents, named bulky-bulky ketones, were successfully reduced to their corresponding optically enriched alcohols by using various mutants of Thermoanaerobacter pseudoethanolicus secondary alcohol dehydrogenase (TeSADH). Substituted 2-tetralones, in particular, were reduced to 2-tetralols with high conversion and high enantioselectivity. The pharmacological importance of substituted 2-tetralols as key drug-building blocks makes our biocatalytic reduction method a highly essential tool. We showed that changing the position of the substituent on the aromatic ring of 2-tetralones impacts their binding affinity and the reaction maximum catalytic rate. Docking studies with several TeSADH mutants explain how the position of the substituent on the tetralone influences the binding orientation of substituted 2-tetralones and their reaction stereoselectivity. [ABSTRACT FROM AUTHOR]

The catalytic asymmetric synthesis of both α-substituted and α,α-disubstituted (quaternary) β-tetralones through direct α-functionalization of the corresponding β-tetralone precursor remains elusive. A designed Brønsted base-squaramide bifunctional catalyst promotes the conjugate addition of either unsubstituted or α-monosubstituted β-tetralones to nitroalkenes. Under these reaction conditions, not only enolization, and thus functionalization, occurs at the α-carbon atom of the β-tetralone exclusively, but adducts including all-carbon quaternary centers are also formed in highly diastereo- and enantioselective manner. [ABSTRACT FROM AUTHOR]

α-Arylcyclobutanones display unique reactivity that makes them valuable synthetic intermediates and target molecules. We describe the preparation of α-aryl- and α-heteroarylcyclobutanones through a direct α-arylation reaction. Problematic fragmentations are avoided by the use of LiOtBu, which promotes a rapid but reversible self-aldol reaction that slowly releases the enolate required for α-arylation. We also demonstrate the ring expansion of α-arylcyclobutanones, a process that is highlighted in the stereoselective synthesis of 1-methoxy coniothyrinone D. [ABSTRACT FROM AUTHOR]

High-performance liquid chromatography (HPLC) is a powerful method in the area of chiral separation. In this study, a method of HPLC using carboxymethyl-β-cyclodextrin (CM-β-CD) as chiral selector was developed for enantioseparation of nine indanone and tetralone derivatives. The separation was performed on a conventional C18 column. The optimal mobile phase was a mixture of methanol and 0.05 mol/L phosphate buffer at pH 1.8 (55:45, v/v) containing 22.9 mmol/L CM-β-CD. Under such conditions, the resolutions of all analytes were over 1.8 except for Compound F. The results of the study indicate the presence of a complex with 1:1 stoichiometry of the inclusion complex. In addition, it can be inferred from thermodynamic analysis that the behavior of formation of the inclusion complex and enantioseparation occurred simultaneously, while they were driven by different forces. The effect of analyte structure is also discussed. [ABSTRACT FROM AUTHOR]

The article discusses the isolation, structural study, and biological activities of nine compounds isolated from the EtOAc extract of the gorgonian-derived fungus Chaetomium globosum. It reports that the compounds included six cytochalasins, one tetralone derivative, one isocoumarin derivative and one O-phthalate derivative and their structures were elucidated by spectroscopic methods. Also mentioned are the antibacterial activities and lethality towards brine shrimp of these compounds.

An efficient method for the conversion of available plant allylpolyalkoxybenzenes into unsubstituted and arylsubstituted polymethoxylated aryldihydrobenzo[ g ]indazoles, analogues of combretastatin A4, has been developed. The selective demethylation of target compounds resulted in indazoles with different position of OH-group. Their structure was confirmed by X-ray analysis. A sea urchin embryo assay revealed the lack of tubulin-related antimitotic activity of aryldihydrobenzo[g]indazoles with systemic toxicity of a compound featuring OH group and 1-unsubstituted pyrazole ring. [Display omitted] • Synthesis of polyalkoxyaryldihydrobenzoindazoles, cis -analogues of combretastatin. • Efficient cyclization method for synthesis of polyalkoxytetralones. • Plant allylpolyalkoxybenzenes apiol and dillapiol were used as starting material. • X-ray diffraction study of selected compounds. • Evaluation of biological activity on the sea urchin embryo model. [ABSTRACT FROM AUTHOR]

An unprecedented defluorocyclization of perfluorobutyl tetralones with Na 2 S·9H 2 O was developed for the synthesis of trifluoromethyl 1,2-dithioles, which provided chemists novel access to biologically and pharmaceutically relevant organofluorides. Successive C(sp 3 )-F bond functionalization at the perfluoroalkyl chain is vital for the formation of four C-H/C-S/S-S bonds and a five-membered S-heterocycle assembly. Cheap, weakly toxic, and odorless inorganic sulfide Na 2 S·9H 2 O acts as both a disulfurating precursor and a hydrodefluorinating reagent in this tandem multi-bond-interconverting reaction.

A series of novel chalcones were synthesized by the Claisen-Schmidt condensation reaction of tetralones and 5-/6-indolecarboxaldehydes. Treatment of human lung cancer cell line harboring KRAS mutation (A549) with the chalcones induced dose-dependent apoptosis. Cell cycle analyses and Western blotting suggested the critical role of the chalcones in interrupting G2/M transition of cell cycle. SAR study demonstrated that substituent on the indole N atom significantly affects the anticancer activity of the chalcones, with methyl and ethyl providing the more active compounds (EC 50 : 110–200 nM), Compound 1g was found to be >4-fold more active in the A549 cells (EC 50 : 110 nM) than in prostate (PC3) or pancreatic cancer (CLR2119, PAN02) cells. Furthermore, compound 1l selectively induced apoptosis of lung cancer cells A549 (EC 50 : 0.55 μM) but did not show measurable toxicity in the normal lung bronchial epithelial cells (hBEC) at doses as high as 10 μM, indicating specificity towards cancer cells. [ABSTRACT FROM AUTHOR]

The synthesis of 2-tetralones through the cyclization of δ-aryl-β-dicarbonyl substrates by using CAN is described. Appropriately functionalized aromatic substrates undergo intramolecular cyclizations generating 2-tetralone derivatives in moderate to good yields. DFT computational studies indicate that successful formation of 2-tetralones from δ-aryl-β-dicarbonyl radicals is dependent on the stability of the subsequent cyclohexadienyl radical intermediates. Furthermore, DFT computational studies were used to rationalize the observed site selectivity in the 2-tetralone products.

Graphical abstract Highlights • Synthesis of 2-tetralones has been reported. • Palladium catalyzed intramolecular carbonyl α-arylation has been applied. • 2-Tetralone-3-carboxylate has been converted to more complex ring systems. Abstract The synthesis of 2-tetralone analogues via the palladium-catalyzed intramolecular α-arylation of 2-(2-bromoaryl)-1,3-dicarbonyl compounds has been described. [ABSTRACT FROM AUTHOR]