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This study aimed to analyze the cytotoxic and apoptotic effects of isoxazoline derivatives with monoterpene scaffold

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In the current study, natural (R)-carvone was utilized as a starting material for the efficient synthesis of two series of isoxazoline derivatives bearing the 1,3,4-thiadiazole moiety. The new compounds were obtained in good yields and were characterized by

The present work focuses on the synthesis, structural characterization and electrochemical investigation of some heterocyclic compounds prepared from d -limonene. Firstly, 3-acetylisoxazoline was synthesized from d -limonene, this precursor is then converted to its thiosemicarbazone derivatives which were then cyclized to produce their corresponding thiazolidine-4-ones. The obtained compounds were characterized by FT-IR, 1H NMR, 13C NMR and mass spectrometric techniques. Further, DFT quantum chemical studies were also used to interpret the structural properties of the compounds using the B3LYP/6–311++G (d, p) basis set. The obtained results from experimental and theoretical studies were in good agreement showing that compounds bearing both isoxazoline and thiazolidine-4-one moieties act as good corrosion inhibitors for stainless steel in 1 M sulfuric acid.

A novel series of 1,2,3-triazole-thiazolidinone-carvone hybrid compounds has been designed and synthesized using the copper-catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition (CuAAC) process based on (R)-Carvone-O-propargylated 5-hydroxybenzylidene-thiazolidin-4-one derivative as starting material. All compounds were characterized and identified based on their NMR and HRMS spectroscopic data. HMBC correlations confirm that under the CuAAC reaction conditions, only the 1,4-disubstituted triazole regioisomers were formed. The targeted 1,2,3-triazole-thiazolidinone-carvone hybrids and their precursors were evaluated for their cytotoxic activity against four human cancer cell lines, including fibrosarcoma (HT-1080), lung carcinoma (A-549), and breast carcinoma (MCF-7 and MDA-MB-231). The obtained data showed that most of these compounds have moderate anti-proliferative activity with IC50 values between 15.04 ± 0.71 and 42.22 ± 1.20 µM. The mechanism of action of the most active compounds 14e and 14f suggested that they induce apoptosis through caspase-3/7 activation, and the compound 14e elicited S-phase arrest, while compound 14f evoked G2/M phase blockade. The molecular docking confirmed that compounds 14e and 14f were nicely bonded with caspace-3 leading up to stable protein-ligand complexes.

The title compound is a pure diastereoisomer built up from a central five-membered di­hydro­isoxazole ring substituted in the 3 and 5 positions by a p-chloro­phenyl group and a cyclo­hex-2-enone ring. The cyclo­hex-2-one and the isoxazoline rings both exhibit an envelope conformation. The crystal packing features C—H⋯O, C—H⋯N and C—H⋯π inter­actions., The title compound, C17H18ClNO2, was prepared and isolated as a pure diastereoisomer, using column chromatography followed by a succession of fractional crystallizations. Its exact structure was fully identified via 1H NMR and confirmed by X-ray diffraction. It is built up from a central five-membered di­hydro­isoxazole ring to which a p-chloro­phenyl group and a cyclo­hex-2-enone ring are attached in the 3 and 5 positions. The cyclo­hex-2-one and isoxazoline rings each exhibit an envelope conformation. The crystal packing features C—H⋯O, C—H⋯N and C—H⋯π inter­actions, which generate a three-dimensional network.

The title compound, C22H28O3, was prepared by a direct acetylation reaction of naturally occurring totarolenone. The molecule contains three fused rings, which exhibit different conformations. The central ring has a half-chair conformation, while the non-aromatic oxo-substituted ring has a screw-boat conformation. In the crystal, molecules are linked by C—H...O hydrogen bonds and C—H...π interactions, forming sheets parallel to the bc plane. The carbonyl O atoms and the C atom at the 6-position of the cyclohexene ring are each disordered over two sets of sites with major occupancy components of 0.63 (7) and 0.793 (14), respectively.

International audience; New series of chiral isoxazoles and pyrazoles with monoterpenic skeleton, have been efficiently synthesized from naturally occurring (R)-Carvone, using 1,3-dipolar cycloaddition reaction with arylonitrile oxides and diarylnitrilimines. The reaction showed high peri-, and regioselectivity. In the case of diarylnitrilimines, the reaction revealed to be highly diastereoselective. The structure of the newly synthesized adducts were fully established via spectroscopic analysis and X-ray crystallography. A succinct theoretical study was used to explain the diastereoselectivity experimentally observed. All the newly synthesized monoterpenic isoxazole and pyrazole derivatives were evaluated for their cytotoxic activity against human HT1080, MCF-7 and A-549 cancer cells.

The synthesis of three new polysubstituted monoterpenic thiazolidin-4-ones, namely (Z)-3-methyl-2-{(E)-[(1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene]hydrazinylidene}thiazolidin-4-one, C14H21N3OS (2), (2Z,5Z)-5-[(dimethylamino)methylidene]-2-{(E)-[(1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene]hydrazinylidene}thiazolidin-4-one, C16H24N4OS (3), and (2Z,5Z)-5-[(dimethylamino)methylidene]-3-methyl-2-{(E)-[(1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene]hydrazinylidene}thiazolidin-4-one, C17H26N4OS (4), is reported, starting from the corresponding thiosemicarbazones obtained from naturally occurring (R)-camphor. All the newly obtained thiazolidin-4-ones have been fully characterized by HRMS and 1H and 13C (1D and 2D) NMR spectroscopy. Two of them, i.e. 2 and 3, were identified by single-crystal X-ray crystallography, confirming the synthetic pathway and the spectroscopic analyses. In 3, there are two roughly identical molecules within the asymmetric unit with the same absolute configuration. These two molecules are linked through N—H...O hydrogen bonds, building an R 2 2(8) graph-set motif.

Background: A series of chalcones and flavones were synthesized from 2’-hydroxyacetophenone and substituted aromatic aldehydes via Simmons-Schmidt condensation followed by oxidative cyclization. Methods: Characterization of the obtained structures was established on the basis of their spectroscopic data. The synthesized compounds were screened for their antimicrobial activities against five bacterial strains (Citrobacter freundii, Staphylococcus aureus, Listeria monocytogenes, Salmonella braenderup, Escherichia coli.) and two fungal strains (Candida albicans, Candida krusei). Results: The in vitro bioassay results indicated that some target compounds displayed moderate (4d, 4e) to high (4a) antifungal activity against the pathogenic fungi C. albicans and C. krusei. Conclusion: For the antibacterial activity, only products 3d and 4d showed a weak antibacterial activity. These compounds can lead to the design of new drugs with specific antifungal activity.

There are two independent molecules (AandB) in the asymmetric unit of the title compound, C11H19N3S. In moleculeB, two C atoms and the associated H atoms of the cyclohexene ring are disordered over two sets of sites with a site occupancy ratio of 0.649 (7):0.351 (7). The N—N—C—N fragments of the hydrazinecarbothioamide segments of both molecules are not planar, with a torsion angle of −5.8 (3)° forAand 11.6 (3)° forB. The stability of the conformations of both molecules is aided by the formation of intramolecular N—H...N hydrogen bonds. In the crystal, N—H...S hydrogen bonds link like molecules intoR22(8)A+Bdimers. These dimers are interconnected by additional N—H...S contacts, forming chains along thec-axis direction. The structure was refined as a two-component inversion twin.

The chemical recycling of the poly(ethylene terephthalate), (PET), has been successfully carried out by glycoly- sis in the presence of bis (2-hydroxyethyl) terephthalate (BHET) resulting in the formation of hydroxytelechelic oligomers. These oligomers were then treated with carboxytelechelic poly(!-caprolactone) oligomers of —n = 2300 and —n = 730 g·mol -1 molecular weight, in the absence or presence of the titanium tetrabutyloxide (Ti(OBu)4) as a catalyst to get multiblock copolyesters. The chemical structure of the synthesized copolyesters was investigated by size exclusion chro- matography (SEC) and proton Nuclear Magnetic Resonance ( 1 H NMR) spectroscopy. Moreover the differential scanning calorimetry (DSC) was used to explore their thermal properties. The ester-ester interchange reaction was observed between the two oligopolyesters, was studied and discussed in detail.

The crystal structure of the title compound, dimethyl 2-((2Z,5Z)-5-(2-meth­oxy-2-oxo­ethyl­idene)-2-{(E)-[2-methyl-5-(prop-1-en-2-yl)cyclo­hex-2-enyl­idene]hydrazinyl­idene}-4-oxo­thia­zolidin-3-yl)fumarate displays a conformational disorder which inverts the configuration of the chiral C atom within the cyclo­hexyl­idene ring., The crystal structure and the conformation of the title compound, C22H27N3O7S, were determined from the synthetic pathway and by X-ray analysis. This compound is a new 4-thia­zolidinone derivative prepared and isolated as pure product from thio­semicarbazone carvone. The mol­ecule is built up from an oxo­thia­zolidine ring tetra­substituted by a meth­oxy–oxo­ethyl­idene, a maleate, an oxygen and a cyclo­hexyl­idene–hydrazone. The cyclo­hexyl­idene ring is statistically disordered over two positions, resulting in an inversion of configuration for the substituted carbon.

The title compound, C11H19N3S, was prepared by the reaction of (R)-pulegone with thiosemicarbazide in acidic medium, using ethanol as solvent. The molecule is built up from fused six and five-membered rings. The six-membered ring adopts a chair conformation, while the five-membered ring displays an envelope conformation with the dimethyl-substituted C atom as the flap. The dihedral angle between the mean planes of the two rings is 20.35 (6)°. In the crystal, molecules are linked by N—H...N and N—H...S hydrogen bonds into chains running parallel to [100].

International audience; Highly diastereoselective 1,3-dipolar cycloaddition of in situ generated C,N-diaryl nitrilimines to (1R)-thiocamphor leads to chiral spiro-1,3,4-thiadiazolocamphane derivatives in good yields. The structures and stereochemistries of the new cycloadducts were fully established by spectroscopic methods including X-ray diffraction data. The diastereoselectivity observed in this reaction was explained by means of a brief theoretical study.

A simple and easily synthesis of new generation of N-donor bipyrazolic tripods by coupling of functionalized pyrazole derivatives and an appropriate primary amine derivative via condensation or nucleophilic substitution reaction is presented. The complexation capacity of these compounds towards bivalent metal ions (Hg2+, Cu2+, Pb2+, Cd2+) and alkaline metal ions (Li+, Na+, K+) were investigated using the liquid–liquid extraction process. The percentage limits of extraction were determined by atomic absorption measurements.

The title compounds C11H16Cl2O3 (III) and C11H16Br2O3 (IV) have been prepared from (S)-Limonen. Their crystal structure and absolute configuration have been determined by X-ray analysis which confirmed the 1′S absolute configuration at the cyclopropyl moiety, in agreement with the known absolute configuration of the starting material. Both (III) and (IV) are orthorhombic, space group P212121 with a = 7.2558(4) A (for III) 7.4058(6) A (for IV), b = 9.7885(5) A (for III) 9.7459(7) A (for IV), c = 17.7551(10) A (for III) 18.0354(14) A (for IV), α = 90°, β = 90°, γ = 90° and Z = 4. Absolute configuration determination, via an X-ray crystallographic study, of two optically active cyclopropyl-ketoacids.

The absolute structure of the title compound was determined from the synthetic pathway and by resonant scattering. The compound is a new thia­zolidin-4-one derivative, prepared from (R)-thio­semicarbazone pulegone, and was isolated on crystallization from ethanol as the pure (3aS,6R)-diastereisomer., The title compound, C13H19N3OS, is a new thia­zolidin-4-one derivative prepared and isolated as the pure (3aS,6R)-diastereisomer from (R)-thio­semicarbazone pulegone. It crystallized with two independent mol­ecules (A and B) in the asymmetric unit. The compound is composed of a hexhydro­indazole ring system (viz. a five-membered di­hydro­pyrazole ring fused to a cyclo­hexyl ring) with a thia­zole-4-one ring system attached to one of the pyrazole N atoms (at position 2). The overall geometry of the two mol­ecules differs slightly, with the mean planes of the pyrazole and thia­zole rings being inclined to one another by 10.4 (1)° in mol­ecule A and 0.9 (1)° in mol­ecule B. In the crystal, the A and B mol­ecules are linked via C—H⋯O hydrogen bonds, forming slabs parallel to the ab plane. There are C—H⋯π inter­actions present within the layers, and between the layers, so forming a three-dimensional structure.

New functionalized isoxazolines were effeciently and easily prepared from limonene. The procedure involves a peri‐ and regioselective 1,3‐dipolar cycloaddition of nitrile oxides on the monoterpene external double bond, followed by a highly chemoselective RuCl3‐NaIO4 oxidative cleavage of the internal one. All the newly prepared isoxazolyl‐ketoacids were fully characterized from their spectroscopic data.

Five new cyclopropyl-ketoacids were prepared in good yields from monoterpenic olefines using solid-liquid phase transfer catalysis (SL-PTC) dichlorocyclopropanation reaction followed by oxidative cleavage with RuCl3-NaIO4 system. The nonchlorinated cyclopropanes were obtained by sodium/methanol reduction of the corresponding gem-dichlorocyclopropanes.

Mixed-ligand complexes of ruthenium(III) containing tridentate chiral Schiff-base ligands (H2TDL*s) derived from condensation of either d -glucose amine or l -alanine with 3,5-di-tertiarybutylsalicyldehyde, and triphenylphosphine (PPh3) or 2,2′-bipyridine (bipy) have been synthesized. The ruthenium(III)-complexes, [ R u III Cl ( TD L 1 * ) ( PP h 3 ) 2 ] {( H 2 TD L 1 * = N - 3 , 5 -di- ( tertiarybutyl ) salicylidine- D -glucosamine )},(1) [ R u III Cl ( TD L 2 * ) ( PP h 3 ) 2 ] H 2 TD L 2 * = { N - 3 , 5 -di- ( tertiarybutyl ) salicylidine- L -alanine } (2) and [ R u III ( TD L 2 * ) ( bipy ) H 2 O ] Cl (bipy = 2,2′-bipyridine) (3) were characterized by analytical, spectral (UV–vis and IR), molar conductivity, magnetic moment and electrochemical studies. Complex 1 exhibited remarkable enantioselcetivity toward epoxidation of unfunctionalized alkenes using tert-butylhydroperoxide (t-BuOOH) as terminal oxidant. Styrene, 4-chlorostyrene, 4-methylstyrene, 4-methoxystyrene, 1-methylcyclohexene and 1,2-dihydronaphthalene were effectively converted to their organic epoxides in the 70–95% ee at ambient temperature. A lesser enantioselectivity was observed when complexes 2 and 3 were used in the epoxidation of enlisted alkenes under identical experimental conditions. A mechanism involving intermediacy of a high-valent Ru(V)-oxo species is proposed for the catalytic epoxidation process.

Various chromium VI -catalyzed conditions have been tested to improve the oxidation of Δ 5 -steroids with t -BuOOH to their corresponding 5-en-7-ones. The use of PDC or the association of CrO 3 with an amine as the catalyst and CH 2 Cl 2 or PhCF 3 as the solvent led usually to the best yields. A minor reaction pathway was the epoxidation of the double bond.

The monitoring by UV spectroscopy of the Pd-catalyzed hydrogenolysis in acetonitrile of 2-methyl-2-benzyloxycarbonyl-1-indanone and 2-methyl-2-benzyloxycarbonyl-1-tetralone showed the successive formation of corresponding beta-ketoacids and enols to deliver finally the ketones. Some factors which influence the stability of the intermediates are determined. In contrast to the above benzyl beta-ketoesters, the enol was not detected from benzyl (2-methylinden-3-yl) carbonate.

Bronsted acids induced the intramolecular cyclisation of 3-aryloxypropanoic esters affording 3-methyl-4-chromanones, which have been transformed into the corresponding racemic benzyl β-oxoesters. These latter esters, in the presence of hydrogen and catalytic amounts of both palladium and (endo, endo) aminoborneol, led to optically active chromanones with up to 75% ee through a deprotection–decarboxylation–protonation cascade reaction.

Three racemic α-fluorinated benzyl β-ketoesters have been synthesized by electrophilic fluorination with Selectfluor™. They were submitted to our well established palladium-mediated cascade reaction (deprotection, decarboxylation and protonation of the resulting enolic species) producing optically active α-fluoro ketones. With benzyl 2-fluoro-1-tetralone-2-carboxylate as substrate, ( S )-(−)-2-fluoro-1-tetralone with up to 65% enantiomeric excess was obtained using quinine as the chiral base and Pd/C type 807104 from Merck as the heterogeneous catalyst.

The synthesis and characterization of new N-donor bitriazolic tripods were reported. The in vitro antibacterial and antifungal activities of these products were screened against fungal strain (Candida pelliculosa) and against four bacterial strains (Micrococcus luteus, Bacillus subtilis, Listeria innocua, and Escherichia coli). Biological data revealed the effect of the chemical structure on antimicrobial activity. Molecular docking studies of some compounds showed that they could act as inhibitors for the biotin carboxylase enzyme.

Two unprecedented three-dimensional ruthenium(II) complexes I and II derived from 2-methyl-5-oxo-7-phenyl-3-thioxo-3,4,5,6-tetrahydro-2H-1,2,4-triazepine (HTAZO) and 2-methyl-7-phenyl-3,5-dithioxo-3,4,5,6-tetrahydro-2H-1,2,4-triazepine (H2TAZS) have been prepared by the reaction of these triazepines with [Ru(p-cymene)Cl2]2 in the presence of triethylamine. NMR spectroscopic and X-ray diffraction studies of the structures of the resulting complexes reveal different behavior of HTAZO and H2TAZS in the coordination process.

The addition of various substituted phenols [XC6H4OH, X=H, o-CHO, o-CO2Me, o-CO2CH2Ph, o-CN, m-NHCOMe, m-OMe, p-OMe, p-CHO, p-Cl] to allylic acetates obtained from Baylis–Hillman adducts [RCH(OAc)C(CH2)CO2Et, R=H, n-Pr] has been studied in the presence of a Pd(0) catalyst and/or KF/alumina. In some cases, the use of one of these two reagents was sufficient to promote the OAc/OAr exchange but in general, faster reactions and higher yields were achieved when both reagents were used together. Evidence for two routes, an η3-allylpalladium intermediate and a Michael addition/elimination, was then obtained while a Heck type reaction could be involved under neutral conditions.

Chromium(VI) oxide-catalysed oxidations of alcohols and activated methylenes by aqueous tert -butyl hydroperoxide have been studied using benzotrifluoride as solvent. Comparisons with previous studies showed that this solvent is a valuable alternative to methylene chloride for such reactions. © 2000 Academie des sciences / Editions scientifiques et medicales Elsevier SAS

The chromium oxide-catalyzed oxidation of allylic alcohol - R 1 CH(OH)CR 2 CHR 3 - by ROOH (R= t -Bu, PhCMe 2 ) affords generally a mixture of R 1 COCR 2 CHR 3 and R 1 CHCR 2 COR 3 . The rate of the reaction and the ratio between the two oxidized compounds both depend on the nature of R. It has been concluded that the oxidative species and the reactive intermediates contain this R group.

At 60 °C, the Wells–Dawson tungsten heteropolyacid H 6 P 2 W 18 O 6 2 catalyzes the selective formation of 1,1,3-trimethyl-3-phenylindan from α-methylstyrene.

The crotonisation of 1-tetralone with various alkyl aldehydes under basic conditions led to the corresponding 2-alkylidene-1-tetralones with fair yields and complete stereoselectivities. The E-stereochemistry of the adducts has been determined through their photoisomerisation and by comparison of the 1H NMR spectra.

Heterolytic cleavage of the C–OH bond of various benzylic alcohols has been catalyzed with H6P2W18O62. Alkenes or symmetric ethers are produced, depending on the structure of the substrate.