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Synthesis and evaluation of 1-(benzo[b]thiophen-2-yl)ethanone analogues as novel anti-osteoporosis agents acting on BMP-2 promotor

A novel series of 1-(benzo[b]thiophen-2-yl)ethanone analogues were prepared and evaluated for enhancing BMP-2 expression. Compounds 1-5, 7, 8, 12, 13 and 16, with upregulation rate values of 35.6%, 27.9%, 39.8%, 32.0%, 37.1%, 30.2%, 28.0%, 33.5%, 22.8% and 27.3% in vitro, respectively, at a concentration of 4 muM, exhibited potent effect for enhancing BMP-2 expression. We also found that compounds 1 and 12 produced a dose-dependent increase on bone histology and histomorphometry, and effectively reduced bone defects induced by ovariectomy in an ovariectomized rat model (OVX).

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Abiotic oxidation of petroleum bitumens under natural conditions

Five series of crude oil samples exposed to atmospheric conditions have been analysed at the molecular level, each series comprising several samples originating from the same crude oil but altered to different extents. The aim of our investigation was to compare the specific impact of abiotic oxidation to other alteration processes such as biodegradation, evaporation and water washing. Bulk analyses revealed that increasing alteration is accompanied by an increase in oxygen content which parallels a relative increase of the proportions, as well as of the molecular weights of the macromolecular constituents of the bitumens. Gas chromatographic-mass spectrometric analyses of polar fractions showed the presence of oxygen-containing compounds (steroid ketones, benzothiophenic acids and sulfones) which result from oxidation of petroleum lipids. The hypothesis that part of these oxygenated compounds results from abiotic oxidation processes rather than from biodegradation is supported, notably, by the fact that oxygen incorporation generally occurred without any diastereomeric discrimination. This is also supported by simulation experiments performed on petroleum lipids, which showed that abiotic oxidation induces cleavage reactions affecting C-C and C-S bonds which may intervene in the transformation of geomacromolecules in the environment by degradation (‘depolymerization’). Thus abiotic oxidation may play a major role in the fate of petroleum pollutants in the environment by transforming lipidic organic matter from petroleum into more water soluble and, therefore, more biodegradable constituents. However, these can be more toxic to the environment as the water-soluble fraction may be easily taken up by biota. (C) 2000 Elsevier Science Ltd. Five series of crude oil samples exposed to atmospheric conditions have been analyzed at the molecular level, each series comprising several samples originating from the same crude oil but altered to different extents. The aim of our investigation was to compare the specific impact of abiotic oxidation to other alteration processes such as biodegradation, evaporation and water washing. Bulk analyses revealed that increasing alteration is accompanied by an increase in oxygen content which parallels a relative increase of the proportions, as well as of the molecular weights of the macromolecular constituents of the bitumens. Gas chromatographic-mass spectrometric analyses of polar fractions showed the presence of oxygen-containing compounds (steroid ketones, benzothiophenic acids and sulfones) which result from oxidation of petroleum lipids. The hypothesis that part of these oxygenated compounds results from abiotic oxidation processes rather than from biodegradation is supported, notably, by the fact that oxygen incorporation generally occurred without any diastereomeric discrimination. This is also supported by simulation experiments performed on petroleum lipids, which showed that abiotic oxidation induces cleavage reactions affecting C-C and C-S bonds which may intervene in the transformation of geomacromolecules in the environment by degradation (`depolymerization’). Thus abiotic oxidation may play a major role in the fate of petroleum pollutants in the environment by transforming lipidic organic matter from petroleum into more water soluble and, therefore, more biodegradable constituents. However, these can be more toxic to the environment as the water-soluble fraction may be easily taken up by biota.

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Axially chiral 3,3?-bi(1-benzothiophene)-2,2?-dicarboxylic acid and its derivatives

Ullmann dimerization of substituted methyl 3-X-1-benzothiophene-2-carboxylates 1-7 (X = Cl, Br) gave rise to the corresponding dimeric 3,3?-bi(1-benzothiophene) esters 8-13. Resolution of the title acid 20 by fractional crystallization of its mono- and bisquininium salt afforded pure (R)- and (S)-enantiomers, the optical purity and absolute configuration of which was confirmed by CD spectrometry and by X-ray crystallography. Ullmann dimerization of chiral oxazolines 23 and 24 derived from 2 proceeded without any diastereodifferentiation. Reduction of (R)- and (S)-20 afforded the corresponding (R)- and (S)-diols 29, which served as chiral ligands in a model enantioselective reduction of acetophenone. (R)- and (S)-1-phenylethan-1-ol were formed in 28 and 29% e.e., respectively.

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[1]Benzothieno[3,2-b]furans

A new class of organic chemical compounds [1]benzothieno[3,2-b]furans, are made by O-alkylation of 3-hydroxybenzo[b]thiophene-2-carboxylates with alkyl haloacetates, haloacetonitriles or alpha-halomethyl alkyl ketones, followed by cyclization of the intermediate products with alkali metals or alkali metal alkoxides. The compounds are antimicrobials.

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Benzothiophene-2-carboxamide S,S-dioxides and use

New compounds of the formula (I) STR1 in which R1 -R6 have the meanings given in the description, their preparation and use in plant protection, the protection of materials and in the field of human and veterinary medicine. Formula (I) gives a definition of the compounds which can be prepared by analogous processes, for example from suitable benzothiophene derivatives by oxidation.

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Copper-catalysed ring-opening trifluoromethylation of cyclopropanols

A copper-catalysed ring-opening trifluoromethylation reaction of cyclopropanols has been developed. Various beta-trifluoromethyl ketones are obtained in good to excellent yields under mild reaction conditions. The present method also exhibits good functional-group compatibility. The mechanism of this new ring-opening trifluoromethylation reaction was investigated by radical trapping reactions.

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Solvent-free microwave synthesis of 3-(4-benzo[b]-thiophene-2-carbonyl)-1-piperazinyl-1-benzo[b]thiophen-2-YL-1-propanones. New hetero bis-ligands with potential 5-HT1A serotonergic activity

A novel series of 2-benzothiophenealkylpiperazine derivatives 11 (a-d) with potential affinity at 5-HT1A serotonin receptors have been synthesized via solvent-free, microwave-promoted Michael addition of benzo[b]thiophene piperazine derivatives 6(a-c) to substituted benzo[b]thiophen-2-yl propenones 10(b,c).

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Morita-Baylis-Hillman route to dimethyl 2,3-Dihydrobenzo[b]oxepine-2,4- dicarboxylates and Methyl 2-(2-carbomethoxybenzo[b]furan-3-yl)propanoates from salicylaldehydes

A new synthetic method for dimethyl 2,3-dihydrobenzo[b]oxepine-2,4- dicarboxylates and methyl 2-(2- carbomethoxybenzo[b]furan-3-yl)propanoates by an intramolecular conjugate displacement reaction or an SN2 reaction of acetates of Morita-Baylis-Hillman adducts of methyl (2-formylphenoxy)acetates has been described.

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N,B-bidentate boryl ligand-supported iridium catalyst for efficient functional-group-directed C-H borylation

Convenient silylborane precursors for introducing N,B-bidentate boryl ligands onto transition metals were designed, prepared, and employed in ready formation of irdium(IIl) complexes via Si-B oxidative addition. A practical, efficient catalytic ortho-borylation reaction of arenes with a broad range of directing groups was developed using an in situ generated catalyst from the silylborane preligand 3c and [IrCl(COD)]2.

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Synthesis of ReI tricarbonyl complexes with various sulfur- and oxygen-donating ligands: Crystal structures of two ReI dinuclear structures bridged by S atoms

The synthesis and characterization of two dinuclear complexes, namely fachexacarbonyl- 1kappa3C,2kappa3C-(pyridine-1kappaN)[mu-2,2?-sulfanediyldi(ethanethiolato)- 1kappa2S1,S3:2kappa3S1,S2,S3]dirhenium(I), [Re2(C4H8S3)(C5H5N)(CO)6], (1), and tetraethylammonium fac-tris(mu-2-methoxybenzenethiolato-kappa2S:S)bis[tricarbonylrhenium(I)], (C8H20N)[Re2(C7H7OS)3(CO)6], (2), together with two mononuclear complexes, namely (2,2?-bithiophene-5-carboxylic acid-kappa2S,S?)bromidotricarbonylrhenium(I), (3), and bromidotricarbonyl(methyl benzo[b]thiophene- 2-carboxylate-kappa2O,S)rhenium(I), (4), are reported. Crystals of (1) and (2) were characterized by X-ray diffraction. The crystal structure of (1) revealed two Re?S?Re bridges. The thioether S atom only bonds to one of the ReI metal centres, while the geometry of the second ReI metal centre is completed by a pyridine ligand. The structure of (2) is characterized by three S-atom bridges and an Re ¡¤ ¡¤ ¡¤Re nonbonding distance of 3.4879 (5) A, which is shorter than the distance found for (1) [3.7996 (6)/3.7963 (6) A], but still clearly a nonbonding distance. Complex (1) is stabilized by six intermolecular hydrogen-bond interactions and an O¡¤ ¡¤ ¡¤ O interaction, while (2) is stabilized by two intermolecular hydrogen-bond interactions and two O ¡¤ ¡¤ ¡¤ pi interactions.

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