- Development of effective bidentate diphosphine ligands of ruthenium catalysts toward practical hydrogenation of carboxylic acids
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Hydrogenation of carboxylic acids (CAs) to alcohols represents one of the most ideal reduction methods for utilizing abundant CAs as alternative carbon and energy sources. However, systematic studies on the effects of metal-to-ligand relationships on the catalytic activity of metal complex catalysts are scarce. We previously demonstrated a rational methodology for CA hydrogenation, in which CA-derived cationic metal carboxylate [(PP)M(OCOR)]+ (M = Ru and Re; P = one P coordination) served as the catalyst prototype for CA self-induced CA hydrogenation. Herein, we report systematic trial- and-error studies on how we could achieve higher catalytic activity by modifying the structure of bidentate diphosphine (PP) ligands of molecular Ru catalysts. Carbon chains connecting two P atoms as well as Ar groups substituted on the P atoms of PP ligands were intensively varied, and the induction of active Ru catalysts from precatalyst Ru(acac)3 was surveyed extensively. As a result, the activity and durability of the (PP)Ru catalyst substantially increased compared to those of other molecular Ru catalyst systems, including our original Ru catalysts. The results validate our approach for improving the catalyst performance, which would benefit further advancement of CA self-induced CA hydrogenation.
- Saito, Susumu,Wen, Ke,Yoshioka, Shota
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p. 1510 - 1524
(2021/06/18)
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- Revisiting Hydroxyalkylation of Phenols with Cyclic Carbonates
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Described is a tetrabutylammonium fluoride-mediated hydroxyalkylation reaction of phenols with cyclic carbonates. This operationally simple method enables the synthesis of a variety of aryl β-hydroxyethyl ethers in good to excellent yields with a very small amount of catalyst loading (0.1–1 mol%). Of particular note is the efficient conversion of aromatic diols and phloroglucinol to the corresponding bis- and tris-hydroxyethylated products. To further showcase the versatility of this protocol, guaifenesin was prepared with a single step by the condensation of guaiacol and glycerol carbonate. We also developed a flow ethoxylation process permitting the continuous synthesis of multiflorol. (Figure presented.).
- Kao, Shih-Chieh,Lin, Yi-Ching,Ryu, Ilhyong,Wu, Yen-Ku
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supporting information
p. 3639 - 3644
(2019/07/10)
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- TiO2-Supported Re as a General and Chemoselective Heterogeneous Catalyst for Hydrogenation of Carboxylic Acids to Alcohols
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TiO2-supported Re, Re/TiO2, was found to promote selective hydrogenation of carboxylic acids having aromatic and aliphatic moieties to the corresponding alcohols. Re/TiO2showed superior results compared to other transition-metal-loaded TiO2and supported Re catalysts for selective hydrogenation of 3-phenylpropionic acid. 3-phenylpropanol was produced in 97 % yield under mild conditions (5 MPa H2at 140 °C). Contrary to typical heterogeneous catalysts, Re/TiO2does not lead to the formation of dearomatized byproducts. The catalyst is recyclable and shows a wide substrate scope in the synthesis of alcohols (22 examples; up to 97 % isolated yield).
- Toyao, Takashi,Siddiki, S. M. A. Hakim,Touchy, Abeda S.,Onodera, Wataru,Kon, Kenichi,Morita, Yoshitsugu,Kamachi, Takashi,Yoshizawa, Kazunari,Shimizu, Ken-Ichi
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p. 1001 - 1006
(2017/02/05)
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- Synthesis and inhibitory evaluation of 3-linked imipramines for the exploration of the S2 site of the human serotonin transporter
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The human serotonin transporter is the primary target of several antidepressant drugs, and the importance of a primary, high affinity binding site (S1) for antidepressant binding is well documented. The existence of a lower affinity, secondary binding site (S2) has, however, been debated. Herein we report the synthesis of 3-position coupled imipramine ligands from clomipramine using a copper free Sonogashira reaction. Ligand design was inspired by results from docking and steered molecular dynamics simulations, and the ligands were utilized in a structure-activity relationship study of the positional relationship between the S1 and S2 sites. The computer simulations suggested that the S2 site does indeed exist although with lower affinity for imipramine than observed within the S1 site. Additionally, it was possible to dock the 3-linked imipramine analogs into positions which occupy the S1 and the S2 site simultaneously. The structure activity relationship study showed that the shortest ligands were the most potent, and mutations enlarging the proposed S2 site were found to affect the larger ligands positively, while the smaller ligands were mostly unaffected.
- Brink?, Anne,Larsen, Maja T.,Kolds?, Heidi,Besenbacher, Louise,Kolind, Anders,Schi?tt, Birgit,Sinning, Steffen,Jensen, Henrik H.
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supporting information
p. 2725 - 2738
(2016/06/08)
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- Soot dispersing agent containing the dispersant and lubricating oil composition
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Linked aromatic compounds found to act as potent soot dispersants in lubricating oil compositions; lubricating oil compositions containing such soot dispersants and precursor compounds from which the soot dispersants are derived.
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Paragraph 0138-0141
(2017/01/05)
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- Activity of Fluorine-Containing Analogues of WC-9 and Structurally Related Analogues against Two Intracellular Parasites: Trypanosoma cruzi and Toxoplasma gondii
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Two obligate intracellular parasites, Trypanosoma cruzi, the agent of Chagas disease, and Toxoplasma gondii, an agent of toxoplasmosis, upregulate the mevalonate pathway of their host cells upon infection, which suggests that this host pathway could be a potential drug target. In this work, a number of compounds structurally related to WC-9 (4-phenoxyphenoxyethyl thiocyanate), a known squalene synthase inhibitor, were designed, synthesized, and evaluated for their effect on T. cruzi and T. gondii growth in tissue culture cells. Two fluorine-containing derivatives, the 3-(3-fluorophenoxy)- and 3-(4-fluorophenoxy)phenoxyethyl thiocyanates, exhibited half-maximal effective concentration (EC50) values of 1.6 and 4.9 μm, respectively, against tachyzoites of T. gondii, whereas they showed similar potency to WC-9 against intracellular T. cruzi (EC50values of 5.4 and 5.7 μm, respectively). In addition, 2-[3- (phenoxy)phenoxyethylthio]ethyl-1,1-bisphosphonate, which is a hybrid inhibitor containing 3-phenoxyphenoxy and bisphosphonate groups, has activity against T. gondii proliferation at sub-micromolar levels (EC50=0.7 μm), which suggests a combined inhibitory effect of the two functional groups.
- Chao, María N.,Li, Catherine,Storey, Melissa,Falcone, Bruno N.,Szajnman, Sergio H.,Bonesi, Sergio M.,Docampo, Roberto,Moreno, Silvia N. J.,Rodriguez, Juan B.
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p. 2690 - 2702
(2016/12/23)
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- Br?nsted Acid Catalyzed Functionalization of Aromatic Alcohols through Nucleophilic Substitution of Hydroxyl Group
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The hydroxyl groups of naphthol and tautomerizable phenol derivatives have been substituted by O-, S-, N-, and C-centered nucleophiles under solvent-free reaction conditions. The products are generated in good to excellent yields. para-Toluenesulfonic acid exhibits the best catalytic activity compared to other Bronsted acids. Experimental observations suggest that the reaction proceeds through the intermediacy of the keto tautomer of naphthol. Nucleophilic addition to the carbonyl group followed by elimination of water generates the desired product. The present methodology provides access to substituted naphtho[2,1-b]furan derivatives. The products generated using N-centered nucleophiles can be further transformed to important classes of organic molecules such as benzocarbazole and imidazole derivatives.
- Mishra, Abhishek Kumar,Biswas, Srijit
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p. 2355 - 2363
(2016/04/04)
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- IRREVERSIBLE COVALENT INHIBITORS OF THE GTPASE K-RAS G12C
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Irreversible inhibitors of K-Ras, H-Ras or N-ras protein comprising a G12C mutation are provided. Also disclosed are methods to regulate the activity of K-Ras, H-Ras or N-ras protein comprising G12C mutation and methods to disease mediated by K-Ras, H-Ras or N-ras G12C.
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Page/Page column 65
(2014/09/29)
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- Copper(ii)-catalyzed C-O coupling of aryl bromides with aliphatic diols: Synthesis of ethers, phenols, and benzo-fused cyclic ethers
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A highly efficient copper-catalyzed C-O cross-coupling reaction between aryl bromides and aliphatic diols has been developed employing a cheaper, more efficient, and easily removable copper(ii) catalyst. A broad range of aryl bromides were coupled with aliphatic diols of different lengths using 5 mol% CuCl2 and 3 equivalents of K2CO3 in the absence of any other ligands or solvents to afford the corresponding hydroxyalkyl aryl ethers in good to excellent yields. In this newly developed protocol, aliphatic diols have multilateral functions as coupling reactants, ligands, and solvents. The resulting hydroxyalkyl aryl ethers were further readily converted into the corresponding phenols, presenting a valuable alternative way to phenols from aryl bromides. Furthermore, it was demonstrated that they are useful intermediates for more advanced molecules such as benzofurans and benzo-fused cyclic ethers. This journal is
- Liu, Yajun,Park, Se Kyung,Xiao, Yan,Chae, Junghyun
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supporting information
p. 4747 - 4753
(2014/06/24)
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- Heterogeneous palladium-catalyzed synthesis of aromatic ethers by solvent-free dehydrogenative aromatization: Mechanism, scope, and limitations under aerobic and non-aerobic conditions
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Starting from cyclohexanone derivatives and alcohols, both non-aromatic precursors, aryl ethers could be synthesized in good yields and with good selectivities in the presence of a catalytic amount of Pd/C, in one step, without added solvent, in a reaction vessel open to air. For less reactive substrates, the addition of 1-octene in a closed system under non-aerobic conditions improved the conversion. In addition, the catalyst could be recycled several times with no decrease in the yield of the aryl ether. The process was also used with tetralone derivatives and polyols. Several reactions were performed to propose a mechanism for this transformation. The formation of an enol ether followed by a dehydrogenation reaction seem to be the key steps of this reaction. Aryl ethers were prepared in good yields and with good selectivities in a solvent-free and heterogeneous catalytic dehydrogenative alkylation of cyclohexanones with various alcohols. Three different complementary routes were used, and for the first time, non-aerobic, safe conditions could be used. Moreover, the catalyst could be recycled several times with no decrease in the yield of the aryl ether. Copyright
- Sutter, Marc,Lafon, Romain,Raoul, Yann,Metay, Estelle,Lemaire, Marc
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supporting information
p. 5902 - 5916
(2013/09/23)
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- Ortho-phenylenediamine-based open and macrocyclic receptors in selective sensing of H2PO4-, ATP and ADP under different conditions
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Ortho-phenylenediamine-based open and macrocyclic receptors have been designed and synthesized. The open receptor 1 and the macrocyclic receptor 2 fluorimetrically distinguish H2PO4- from the other anions examined in CH3CN with appreciable binding constant values. As practical applications, they are also sensible to nucleotides in aq. CH3CN (1:1, v/v). The receptor 1 shows significant emission change upon complexation of ATP and ADP. ADP is selectively distinguished by a ratiometric change in emission. In contrast, the macrocyclic receptor 2, under similar conditions, shows good binding with ATP over the others.
- Ghosh, Kumaresh,Saha, Indrajit
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p. 9383 - 9392
(2013/01/15)
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- Lewis acid catalyzed inverse electron-demand diels-alder reaction of 1,2-diazines
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A systematic approach toward Lewis acid catalyzed inverse electron-demand Diels-Alder (IEDDA) reactions of 1,2-diazines is described. The general concept is first investigated by DFT calculations, supported by spectroscopic data, and finally proven in the experiment.
- Kessler, Simon N.,Wegner, Hermann A.
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supporting information; experimental part
p. 4062 - 4065
(2010/11/17)
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- Soot Dispersants and Lubricating Oil Compositions Containing Same
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Linked aromatic compounds found to act as potent soot dispersants in lubricating oil compositions; lubricating, oil compositions containing such soot dispersants and precursor compounds from which the soot dispersants are derived.
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Page/Page column 14
(2008/12/07)
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- Structure-affinity studies for a novel series of homochiral naphtho and tetrahydronaphtho analogues of α1 antagonist WB-4101
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A number of enantiomeric pairs of naphthodioxane, tetrahydronaphthodioxane and naphthoxy analogues of WB-4101 (1) were designed and synthesized in order to improve the selectivity profile of the parent compound, hopefully in favour of the α1a-AR with respect to the other two α1 subtypes and the 5-HT1A receptor. The new compounds 2-8 and, in addition, the two enantiomers of 1 were tested in binding assays on the α1a-AR, α1b-AR, α1d-AR, and the 5-HT1A receptor. Two of them, namely the naphtho- and tetrahydronaphthodioxane derivatives (S)-2 and (S)-3, showed lower, but significantly more specific α1a affinity than (S)-1, while the two enantiomers of the 2-methoxy-1-naphthoxy analogue 6 maintained most of the very high α1a affinity of (S)-1 and its α1a versus α1b selectivity slightly increasing the α1a/α1d and α1a/5HT 1A affinity ratios. The SAR data were evaluated in the light of known α1 subtype pharmacophores and of the α1a-AR binding mode of WB-4101 resultant from literature mutagenesis studies disclosing some interesting consonances with these models.
- Bolchi, Cristiano,Catalano, Paolo,Fumagalli, Laura,Gobbi, Marco,Pallavicini, Marco,Pedretti, Alessandro,Villa, Luigi,Vistoli, Giulio,Valoti, Ermanno
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p. 4937 - 4951
(2007/10/03)
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- Omega-hydrofluoroalkyl ethers, precursor carboxylic acids and derivatives thereof, and their preparation and application
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Normally liquid, omega-hydrofluoroalkyl ether compounds (and selected mixtures thereof) have a saturated perfluoroaliphatic chain of carbon atoms interrupted by one or more ether oxygen atoms. The compounds can be prepare, e.g. by decarboxylation of the corresponding fluoroalkyl ether carboxylic acids and are useful, e.g., in cleaning and drying applications.
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- Synthesis of 5'-polyarene-tethered oligo-DNAs and the thermal stability and spectroscopic properties of their duplexes and triplexes
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Eleven different planar hydroxy alkylated polyarenes 1-11 with different geometry, bulk and electronic characteristics were synthesised, and used for tethering to the 5'-phosphate of a 9-mer and a 18-mer DNA sequences through solid-phase synthesis. The 5'-polyarene-tethered 9-mers 30-40 were tested for their ability to form stable duplexes with four complementary target DNA-strands 25-28 of different length. The 5'-polyarene-tethered 18-mers 44-54 were tested for their ability to form stable triplexes with a 24-mer duplex target 41+42. The T(m) measurements of duplexes at low salt and pH 7.3 showed that the angular nitro phenanthrene and phenanthrene conjugates 31 and 30 gave the highest duplex stabilisations with targets 25 (ΔT(m) 13.8°C and 11.8°C) and 26 (ΔT(m), 12.3°C and 11.9°C). With the mismatch sequence 28, only 30 and 31 gave a high ΔT(m), of 11.6°C and 10.8°C respectively, while lower ΔT(m), values were observed for other conjugates (ΔT(m), -4.0-5.0°C). The T(m) measurements of triplexes between 43-54 and duplex target 41+42 at low salt and pH 7.3, 6.5 and 6.0 without Mg2+ showed that the nitro phenanthrene conjugate 45 gave the best triplex stabilisation (ΔT(m), 4.1-5.4°C). The stabilisation of nitro phenanthrene conjugate 45 compared to phenanthrene conjugate 44 increased more remarkably when Mg2+ was present: 45 (ΔT(m), 15°C), 44 (ΔT(m), 10°C). These results imply that the electron density of the chromophore influences the π-π stacking interactions between the chromophore and nucleobases, and thereby influencing the duplex and triplex stability. Fluorescence measurements on single strand to double strand transition indicated that the 5'-tethered polyarenes are stacked only on the neighbouring nucleobases of the opposite strand. In case of 5'-9-N-ethylphenazinium conjugate 36, a comparative NMR and fluorescence measurement has unambiguously shown that the tethered phenazinium ion is indeed intercalated between the nucleotides of the opposite target strand 26. Thermodynamic calculations showed the most stable ΔG°(298K) for 30, 31(+targets 25, 26, 28) and 35, 36(+targets 25, 26) compared to the blank 29 ΔΔG°(298K) ~-10kJ mol-1). The non-palindromic target 27 was shown by T(m) measurements to form a stable tertiary structure, which was very little affected by addition of any 5'-tethered conjugate, thereby showing the importance of the tertiary structures of an in vivo antisense target and its implication in regard to its bioavailablity to complementary antisense probes.
- Puri, Nitin,Zamaratski, Edouard,Sund, Christian,Chattopadhyaya, Jyoti
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p. 10409 - 10432
(2007/10/03)
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- Synthesis and antiretroviral evaluation of new alkoxy and aryloxy phosphate derivatives of 3'-azido-3'-deoxythymidine
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A series of new ether lipid-3'-azido-3'-deoxythymidine (AZT) conjugates (11a-g) were synthesized and evaluated for anti-HIV activity. The effect of chirality on the antiviral activity was examined through the synthesis of AZT conjugates bearing alkoxypropanols in the lipid portion of the molecule (11a-d). In addition, the long alkyl chain of alkoxyethyl ether lipid-AZT analogs was replaced with aromatic groups (11e-g), and the effect of this structural modification on activity is reported. The results of the biological tests indicate that analogs with a methyl group α to the phosphate moiety (11c,d) exhibit a marked degree of stereoselectivity with regard to their anti-HIV activity. Also, replacement of the long alkyl chain with aromatic groups in the oxyalkyl ether phospholipid-AZT conjugates leads to substantially more potent compounds (11e-g) with an anti-HIV activity comparable to that of AZT.
- Tsotinis, Andrew,Calogeropoulou, Theodora,Koufaki, Maria,Souli, Charikleia,Balzarini, Jan,De Clercq, Erik,Makriyannis, Alexandros
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p. 3418 - 3422
(2007/10/03)
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- Pyridinium derivatives, their production and use
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Novel pyridinium derivatives represented by the formula (I): STR1 wherein STR2 is an optionally substituted pyridinium ring; R1 is a lower alkyl group or aralkyl group; R7 and R10 are independently hydrogen, a lower alkyl group, aryl group or aralkyl group; l is 0 or 1; R5 is a phenylene group or an alkylene group which may be substituted; R11 is an alkyl group or aryl group; X is a group of the formula: --CH2 OCH2 -- or a group of the formula: STR3 wherein R6 is hydrogen, a lower alkyl or a lower alkoxy, and m is an integer of 0 to 3; U is a group of the formula: STR4 wherein R4 is hydrogen, a lower alkyl group, aryl group or aralkyl group; Y and Z are independently a divalent chain group consisting of one to six members which is selected from the class consisting of groups of the formulae: STR5 wherein R is hydrogen, a lower alkyl group, acyl group or aryl group and at least one of which is a group of the formula: STR6 with the proviso that R may be the same or different from each other, or may form a ring together when two or more groups of the formula: STR7 are present, that R may be bonded to R4 when Y contains a group of the formula: STR8 and that R may be bonded to R11 when Z contains a group of the formula: STR9 and W? is a counter anion; are useful as a platelet activating factor antagonist.
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- Naphthyloxyalkylaminobenzoic acids, salts and esters thereof
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This disclosure describes pharmaceutical compositions having hypolipidemic and/or hypoglycemic activity which contain a substituted naphthyloxyalkylaminobenzoic acid or salt or ester thereof.
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- Method of treating lipidemia with aryloxyalkylaminobenzoic acids and esters
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Aryloxyalkylaminobenzoic acids and esters as hypolipemic compounds.
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