- Quorum sensing and nf-κb inhibition of synthetic coumaperine derivatives from piper nigrum
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Bacterial communication, termed Quorum Sensing (QS), is a promising target for virulence attenuation and the treatment of bacterial infections. Infections cause inflammation, a process regulated by a number of cellular factors, including the transcription Nuclear Factor kappa B (NF-κB); this factor is found to be upregulated in many inflammatory diseases, including those induced by bacterial infection. In this study, we tested 32 synthetic derivatives of coumaperine (CP), a known natural compound found in pepper (Piper nigrum), for Quorum Sensing Inhibition (QSI) and NF-κB inhibitory activities. Of the compounds tested, seven were found to have high QSI activity, three inhibited bacterial growth and five inhibited NF-κB. In addition, some of the CP compounds were active in more than one test. For example, compounds CP-286, CP-215 and CP-158 were not cytotoxic, inhibited NF-κB activation and QS but did not show antibacterial activity. CP-154 inhibited QS, decreased NF-κB activation and inhibited bacterial growth. Our results indicate that these synthetic molecules may provide a basis for further development of novel therapeutic agents against bacterial infections.
- Baruch, Yifat,Gopas, Jacob,Kadosh, Yael,Kumar, Rajendran Saravana,Kushmaro, Ariel,Muthuraman, Subramani,Yaniv, Karin
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supporting information
(2021/05/28)
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- Enantioselective Redox-Divergent Chiral Phosphoric Acid Catalyzed Quinone Diels–Alder Reactions
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An efficient enantioselective construction of tetrahydronaphthalene-1,4-diones as well as dihydronaphthalene-1,4-diols by a chiral phosphoric acid catalyzed quinone Diels–Alder reaction with dienecarbamates is reported. The nature of the protecting group on the diene is key to the success of achieving high enantioselectivity. The divergent “redox” selectivity is controlled by using an adequate amount of quinones. Reversible redox switching without erosion of enantioselectivity was possible from individual redox isomers.
- Bernadat, Guillaume,Gelis, Coralie,Masson, Géraldine,Neuville, Luc,Retailleau, Pascal,Varlet, Thomas
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supporting information
p. 8491 - 8496
(2020/04/10)
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- Co-catalysis over a tri-functional ligand modified Pd-catalyst for hydroxycarbonylation of terminal alkynes towards α,β-unsaturated carboxylic acids
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An amphiphilic tri-functional ligand (L1) containing a Lewis acidic phosphonium cation, a phosphino-fragment and a hydrophilic sulfonate anion (-SO3-) enabled Pd(OAc)2 to efficiently co-catalyze the hydroxycarbonylation of terminal alkynes towards α,β-unsaturated carboxylic acids. These incorporated functional groups synergistically promoted the reaction, which proved more effective than the ligands lacking -SO3- and/or phosphonium and the mechanical mixtures of the individual functional groups independently. The molecular structure of Pd-L1 indicated that -SO3- in L1 served as a secondary O-donor ligand with reversible coordinating ability, cooperating with the phosphino-fragment to stabilize the Pd-catalyst. The in situ FT-IR analysis verified that the formation and stability of Pd-H active species in charge of hydroxycarbonylation were dramatically facilitated by the presence of L1. It was believed that, over the L1-based Pd-catalyst, H2O was cooperatively activated by the Lewis acidic phosphonium via "acid-base pair" interaction (H2O → P(v)+) and by the hydrophilic SO3-via hydrogen bonding (SO3-?H2O), giving rise to the formation of dimeric and mono-nuclear Pd-H species driven by reversible SO3--coordination. In addition, the L1-based Pd-catalyst could be immobilized in the ionic liquid [Bmim]NTf2 for six-run recycling uses without obvious activity loss and detectable metal leaching.
- Yang, Da,Liu, Huan,Liu, Lei,Guo, Wen-Di,Lu, Yong,Liu, Ye
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p. 5336 - 5344
(2019/10/11)
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- MANUFACTURING METHOD OF α,β-UNSATURATED CARBOXYLIC ACID
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PROBLEM TO BE SOLVED: To provide a manufacturing method which can get α,β-unsaturated carboxylic acid at a high yield by liquid phase oxidation of α,β-unsaturated aldehyde by oxygen or air with a handy metal catalyst under a mild reaction condition. SOLUTION: Preferably under a presence of organic solvent, α,β-unsaturated carboxylic acid is manufactured by oxidation of α,β-unsaturated aldehydes and oxygen or air under a presence of an iron salt catalyst and a catalyst of alkali metal salt of carboxylic acid. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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Paragraph 0050-0052
(2018/10/16)
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- Method for synthesizing alpha, beta-unsaturated acid by using formic acid and alkine
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The invention relates to a method for synthesizing alpha, beta-unsaturated acid by using formic acid and alkine, in particular to a method for synthesizing alpha, beta-unsaturated acid by using formic acid and alkine under the effect of a nickel catalyst. The consumption of the catalyst is 0.01 to 2 mol percent of the quantity of a substrate substance; the consumption of estolide is 3 to 30 mol percent of the quantity of the substrate substance; the pressure of acetylene gas is 1 to 10 MPa; the reaction temperature is 25 to 100 DEG C; the reaction time is 5 to 12 hours. The method has the advantages that the existing alkine hydrocarboxylation defects are overcome; the use of toxic carbon monoxide gas does not needed; the reaction conditions of the whole process are mild; the efficiency is high; the selectivity is good; the method belongs to a method for preparing the alpha, beta-unsaturated acid with the advantages that the method conforms to green chemistry and has good application aspects; good industrial application prospects are realized.
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Paragraph 0024
(2016/10/27)
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- Nickel-catalyzed hydrocarboxylation of alkynes with formic acid
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A protocol for nickel-catalyzed hydrocarboxylation of alkynes with formic acid was developed. The protocol allowed for highly efficient synthesis of acrylic acid with a TON of up to 7700.
- Hou, Jing,Yuan, Ming-Lei,Xie, Jian-Hua,Zhou, Qi-Lin
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supporting information
p. 2981 - 2984
(2016/06/06)
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- Palladium(0)-Catalyzed Methylcyclopropanation of Norbornenes with Vinyl Bromides and Mechanism Study
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An unusual methylcyclopropanation from [2 + 1] cycloadditions of vinyl bromides to norbornenes catalyzed by Pd(OAc)2/PPh3 in the presence of CH3ONa and CH3OH has been established. A methylcyclopropane subunit was installed by a 3-fold domino procedure involving a key protonation course. Preliminary deuterium-labeling studies revealed that the proton came from methyl of CH3OH and also exposed an additional hydrogen/deuterium exchange process. These two proton-concerned reactions were fully chemoselective.
- Mao, Jiangang,Xie, Hujun,Bao, Weiliang
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supporting information
p. 3678 - 3681
(2015/08/18)
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- Microbial synthesis of plant oxylipins from γ-linolenic acid through designed biotransformation pathways
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Secondary metabolites of plants are often difficult to synthesize in high yields because of the large complexity of the biosynthetic pathways and challenges encountered in the functional expression of the required biosynthetic enzymes in microbial cells. In this study, the biosynthesis of plant oxylipins - a family of oxygenated unsaturated carboxylic acids - was explored to enable a high-yield production through a designed microbial synthetic system harboring a set of microbial enzymes (i.e., fatty acid double-bond hydratases, alcohol dehydrogenases, Baeyer-Villiger monooxygenases, and esterases) to produce a variety of unsaturated carboxylic acids from γ-linolenic acid. The whole cell system of the recombinant Escherichia coli efficiently produced (6Z,9Z)-12-hydroxydodeca-6,9-dienoic acid (7), (Z)-9-hydroxynon-6-enoic acid (15), (Z)-dec-4-enedioic acid (17), and (6Z,9Z)-13-hydroxyoctadeca-6,9-dienoic acid (2). This study demonstrated that various secondary metabolites of plants can be produced by implementing artificial biosynthetic pathways into whole-cell biocatalysis.
- Kim, Sae-Um,Kim, Kyoung-Rok,Kim, Ji-Won,Kim, Soomin,Kwon, Yong-Uk,Oh, Deok-Kun,Park, Jin-Byung
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p. 2773 - 2781
(2015/03/30)
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- Inhibition of human cytochrome P450 2E1 and 2A6 by aldehydes: Structure and activity relationships
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The purpose of this study was to probe active site structure and dynamics of human cytochrome P4502E1 and P4502A6 using a series of related short chain fatty aldehydes. Binding efficiency of the aldehydes was monitored via their ability to inhibit the binding and activation of the probe substrates p-nitrophenol (2E1) and coumarin (2A6). Oxidation of the aldehydes was observed in reactions with individually expressed 2E1, but not 2A6, suggesting alternate binding modes. For saturated aldehydes the optimum chain length for inhibition of 2E1 was 9 carbons (KI = 7.8 ± 0.3 μM), whereas for 2A6 heptanal was most potent (KI = 15.8 ± 1.1 μM). A double bond in the 2-position of the aldehyde significantly decreased the observed KI relative to the corresponding saturated compound in most cases. A clear difference in the effect of the double bond was observed between the two isoforms. With 2E1, the double bond appeared to remove steric constraints on aldehyde binding with KI values for the 5-12 carbon compounds ranging between 2.6 ± 0.1 μM and 12.8 ± 0.5 μM, whereas steric effects remained the dominant factor in the binding of the unsaturated aldehydes to 2A6 (observed KI values between 7.0 ± 0.5 μM and >1000 μM). The aldehyde function was essential for effective inhibition, as the corresponding carboxylic acids had very little effect on enzyme activity over the same range of concentrations, and branching at the 3-position of the aldehydes increased the corresponding KI value in all cases examined. The results suggest that a conjugated π-system may be a key structural determinant in the binding of these compounds to both enzymes, and may also be an important feature for the expansion of the active site volume in 2E1.
- Kandagatla, Suneel K.,Mack, Todd,Simpson, Sean,Sollenberger, Jill,Helton, Eric,Raner, Gregory M.
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p. 195 - 202
(2014/07/21)
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- Palladium(0)-catalyzed methylenecyclopropanation of norbornenes with vinyl bromides
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Highly strained methylenecyclopropane derivatives have been achieved via a novel and efficient Pd(0)-catalyzed domino reaction. The formal [2 + 1] cycloaddition reaction of vinyl bromides to norbornenes involves a Heck-type coupling and a C(sp2)-H bond activation.
- Mao, Jiangang,Bao, Weiliang
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supporting information
p. 2646 - 2649
(2014/06/09)
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- Cu-catalyzed formal methylative and hydrogenative carboxylation of alkynes with carbon dioxide: Efficient synthesis of α,β-unsaturated carboxylic acids
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The sequential hydroalumination or methylalumination of various alkynes catalyzed by different catalyst systems, such those based on Sc, Zr, and Ni complexes, and the subsequent carboxylation of the resulting alkenylaluminum species with CO2 catalyzed by an N-heterocyclic carbene (NHC)-copper catalyst have been examined in detail. The regio- and stereoselectivity of the overall reaction relied largely on the hydroalumination or methylalumination reactions, which significantly depended on the catalyst and alkyne substrates. The subsequent Cu-catalyzed carboxylation proceeded with retention of the stereoconfiguration of the alkenylaluminum species. All the reactions could be carried out in one-pot to afford efficiently a variety of α,β- unsaturated carboxylic acids with well-controlled configurations, which are difficult to construct by previously reported methods. This protocol could be practically useful and attractive because of its high regio- and stereoselectivity, simple one-pot reaction operation, and the use of CO 2 as a starting material. Copyright
- Takimoto, Masanori,Hou, Zhaomin
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supporting information
p. 11439 - 11445
(2013/09/02)
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- Epoxidation of bromoallenes connects red algae metabolites by an intersecting bromoallene oxide-Favorskii manifold
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DMDO epoxidation of bromoallenes gives directly α,β-unsaturated carboxylic acids under the reaction conditions. Calculated (ωB97XD/6- 311G(d,p)/SCRF = acetone) potential energy surfaces and 2H- and 13C-labeling experiments are consistent with bromoallene oxide intermediates which spontaneously rearrange via a bromocyclopropanone in an intersecting bromoallene oxide-Favorskii manifold.
- Christopher Braddock,Clarke, James,Rzepa, Henry S.
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supporting information
p. 11176 - 11178
(2013/11/19)
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- Efficient synthesis of the odourant, 2-nonen-4-olide
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A three-step synthesis of 2-nonen-4-olide starting from heptanal is reported. (E)-3-Nonenoic acid, prepared by Knoevenagel condensation of malonic acid and heptanal, was oxidised by performic acid, a process accompanied by lactonisation, to give 3-hydroxynonan-4-olide in 85% yield. This lactone when reacted with MsCl in the presence of Et3N gave, by elimination, 2-nonen-4-olide in 88% yield. The overall yield was 75%. The odour of the product was evaluated by GC-olfactory analysis and sniffing blotter confirming an oily, coconut-like, and rancid odour.
- Dai, Yi-Feng,Tian, Hong-Yu,Sun, Bao-Guo,Sun, Yu-Mei,Chen, Hai-Tao,Liu, Xiao-Yu
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p. 495 - 496
(2012/10/29)
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- Stereoselective synthesis of α,β-unsaturated carboxylic acids from alkynes using the Fe(CO)5/t-BuOK/AcOH/CH2Cl 2 reagent system
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Reactive iron carbonyl species generated in situ using the Fe(CO) 5/t-BuOK/CH3COOH/CH2Cl2 reagent system reacts with alkynes to give the corresponding α,β-unsaturated carboxylic acids after CuCl2·2H2O oxidation with some regio and stereoselectivity.
- Beesu, Mallesh,Periasamy, Mariappan
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experimental part
p. 30 - 33
(2012/04/17)
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- Engineering the nucleotide coenzyme specificity and sulfhydryl redox sensitivity of two stress-responsive aldehyde dehydrogenase isoenzymes of Arabidopsis thaliana
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Lipid peroxidation is one of the consequences of environmental stress in plants and leads to the accumulation of highly toxic, reactive aldehydes. One of the processes to detoxify these aldehydes is their oxidation into carboxylic acids catalyzed by NAD(P)+-dependent ALDHs (aldehyde dehydrogenases). We investigated kinetic parameters of two Arabidopsis thaliana family 3 ALDHs, the cytosolic ALDH3H1 and the chloroplastic isoform ALDH3I1. Both enzymes had similar substrate specificity and oxidized saturated aliphatic aldehydes. Catalytic efficiencies improved with the increase of carbon chain length. Both enzymes were also able to oxidize α,β-unsaturated aldehydes, but not aromatic aldehydes. Activity of ALDH3H1 was NAD+-dependent, whereas ALDH3I1 was able to use NAD+ and NADP+. An unusual isoleucine residue within the coenzyme-binding cleft was responsible for the NAD +-dependence of ALDH3H1. Engineering the coenzyme-binding environment of ALDH3I1 elucidated the influence of the surrounding amino acids. Enzyme activities of both ALDHs were redox-sensitive. Inhibitionwas correlatedwith oxidation of both catalytic and noncatalytic cysteine residues in addition to homodimer formation. Dimerization and inactivation could be reversed by reducing agents. Mutant analysis showed that cysteine residues mediating homodimerization are located in the N-terminal region. Modelling of the protein structures revealed that the redox-sensitive cysteine residues are located at the surfaces of the subunits. The Authors Journal compilation
- Stiti, Naim,Adewale, Isaac O.,Petersen, Jan,Bartels, Dorothea,Kirch, Hans-Hubert
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experimental part
p. 459 - 471
(2012/06/01)
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- Palladium(II)-catalyzed selective oxidation of α,β-unsaturated aldehydes to α,β-unsaturated carboxylic acids with hydrogen peroxide
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Palladium(II)-catalyzed chemoselective oxidation of αβ- unsaturated aldehydes with hydrogen peroxide to give Oα,β-unsaturated carboxylic acids was performed. Cinnamaldehyde was effectively catalyzed by palladium(II) trifluoroacetate to generate cinnamic acid in 92% yield under organic solvent-free conditions. The reaction appears to be applicable to various α,β-unsaturated aldehydes. Copyright
- Kon, Yoshihiro,Imao, Daisuke,Nakashima, Takuya,Sato, Kazuhiko
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supporting information; experimental part
p. 430 - 431
(2010/03/04)
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- Rhodium(I)-catalyzed carboxylation of aryl- and alkenylboronic esters with CO2
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When the esters of arylboronic acids with 2,2-dimethylpropan-1,3-diol were treated with a catalytic amount of [Rh(OH)(cod)]2 in the presence of 1,3-bis(diphenylphosphino)propane and CsF in dioxane at 60 °C under carbon dioxide atmosphere, the benzoic acid derivatives were obtained in good yields. Reactions of alkenylboronic esters also proceeded under similar conditions to give α,β-unsaturated carboxylic acids. As these boronic esters are now easily available through coupling or direct borylation reactions, this method would be a useful method for the preparation of various functionalized aryl- and alkenyl-carboxylic acids. Copyright
- Ukai, Kazutoshi,Aoki, Masao,Takaya, Jun,Iwasawa, Nobuharu
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p. 8706 - 8707
(2007/10/03)
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- Iododifluoromethyl alkenes [ICF2CH=CHR]: A labile system generated from 1,1-difluoro-1,3-diiodoalkanes and its trapping with nucleophiles
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Treatment of 1,1-difluoro-1,3-diiodoalkanes (ICF2CH2CHIR1, 1) with NEt3 in various solvents or with KF/Al2O3/CH3CN gave no alkenes (ICF2CH=CHR1, 2), whereas with NaOH afforded α,β-unsaturated carboxylic acids, although a signal of 2 in 19F NMR spectroscopy could be observed momentarily sometimes. However, the labile 2 can be trapped either with thiolate or phenoxide ions. The former reaction gives a mixture of CF2=CHCH(SR)R1 and RSCF2CH=CHR1, whereas the latter affords only ArOCF2CH=CHR1. The nucleophilic substitution of the bromoanalogues, BrCF2CH2CHBrR1 and BrCF2CH=CHR1, has also been investigated. A mechanism involving SN2′ and an allene intermediate is proposed.
- Guo,Chen
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- Nickel-mediated regio- and chemoselective carboxylation of alkynes in the presence of carbon dioxide
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Alkynes are carboxylated in a highly regio- and chemoselective manner in the presence of Ni(cod)2, DBU, and CO2 to give the carboxylated products in good yields. The reaction was carried out under very mild conditions (CO2 1 atm, 0°C) in the presence of a stoichiometric amount of alkynes, conjugated enynes, or diynes. The high selectivity observed in the reaction would be explained in terms of the stability and the reactivity of the intermediates.
- Saito, Shinichi,Nakagawa, Satomi,Koizumi, Toru,Hirayama, Kyoko,Yamamoto, Yoshinori
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p. 3975 - 3978
(2007/10/03)
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- The free-radical addition of phenyl trichloromethyl selenide to alkenes: A new method for the regioselective carboxylation of alkenes
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The free-radical addition of phenyl trichloromethyl selenide to alkenes affords 2-phenylseleno-1-trichloromethylalkanes, which can be converted into α,β-unsaturated carboxylic acids or amides by base-promoted dehydrochlorination, followed by [2,3]sigmatropic rearrangement of the corresponding selenoxides in the presence of water or diethylamine, respectively.
- Back, Thomas G.,Minksztym, Kazimierz
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p. 1759 - 1760
(2007/10/03)
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- Indole derivatives useful as testosterone 5α-reductase inhibitors
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A compound of the formula (I): STR1 wherein R 1 is an optionally protected carboxy(lower)alkyl, R 2 is a hydrogen, an optionally substituted aryl or a carboxy,X is a bond, --0--, --NH-- or a cycloalkylene, andY is an alkylene which may be interrupted by an oxygen atom, an alkenylene or an alkadienylene,or a pharmaceutically acceptable salt thereof. The compound of the present invention is useful as a testosterone 5α-reductase inhibitor and effective against testosterone 5α-reductase-mediated diseases such as prostatism, prostatic hypertrophy, prostatic cancer, alopecia, hirsutism (e.g. female hirsutism), androgenic alopecia (or male-pattern baldness), acne (e.g. acne vulgaris, pimple), and other hyperandrogenisms.
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- SYNTHESIS OF (E)-VINYLIC TELLURIDES AND THEIR TRANSFORMATION INTO α,β-UNSATURATED ESTERS AND CARBOXYLIC ACIDS
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Zirconium alkenyls and dienyls of E configuration, obtained by the hydrozirconation of alkynes or conjugated enynes containing a terminal triple bond undergo the Zr/Te exchange reaction by treatment with C4H9TeBr or C4H9TeI in THF at -78 deg C.The Zr/Te exchange reaction proceeds with total retention of configuration and with complete stereoselectivity at the carbon 1, furnishing (E)-butyltelluro alkenes (64-86percent yields) and (E)-1-butyltelluro-1,3-dienes (68-75percent yields).Vinylic tellurides were transformed into α,β-unsaturated esters and carboxylic acids with total retention of the regio- and stereochemistry via vinyl lithium intermediates.
- Dabdoub, Miguel J.,Begnini, Mauro L.,Cassol, Tania M.,Guerrero, Palimecio G.,Silveira, Claudio C.
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p. 7623 - 7626
(2007/10/02)
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- Asymmetric synthesis of γ-hydroxy α, β-unsaturated amides via an AD-elimination process; synthesis of (+)-Coriolic acid
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An efficient, asymmetric synthetic route to γ-hydroxy α,β-imsaturated ketone and/or aldehyde equivalents is described. Thus, 3,4-dihydroxy N-methoxy-N-methyl amides are treated in a one pot process with thionyl chloride followed by DBU to give the corresponding γ-hydroxy α,β-unsaturated amides in good yields. Based on this methodology, a short sequence leading to natural (+)-Coroilic acid is presented.
- Bennani, Youssef L.,Barry Sharpless
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p. 2083 - 2086
(2007/10/02)
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- Ligand-directed reaction products in the nickel-catalyzed electrochemical carboxylation of terminal alkynes
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The influence of a series of N and P ligands in the nickel-catalyzed electrochemical carboxylation of 1-octyne has been studied.Different carboxylic acids are obtained depending on the nature of the ancillary ligand, and results afford an example of high ligand-directed product specificity.
- Labbe, Eric,Dunach, Elisabet,Perichon, Jacques
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p. C51 - C56
(2007/10/02)
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- Electrochemical carboxylation of terminal alkynes catalyzed by nickel complexes: unusual regioselectivity
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The electrochemical reduction of the nickel(II) complex Ni(bipy)3(BF4)2 yields an active catalyst for the regioselective functionalization of the 2-position of terminal alkynes with carbon dioxide.A series of α-substituted acrylic acids have been obtained with selectivities of 65-90percent and fair overall yields.
- Dunach, Elisabet,Perichon, Jacques
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p. 239 - 246
(2007/10/02)
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- Geminal and Vicinal 13C-13C Coupling Constants in Carboxylic Acid Derivatives
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Geminal 13C-13C coupling constants in αβ-unsaturated azlactones and the acids and esters derived from their hydrolysis are large and strongly dependent of configuration.Coupling constants in simple 13C1-labelled carboxylic acids are also reported; vicinal couplings show a strong geometric dependence but the geminal couplings depend mainly on hybridisation.
- Chaloner, Penny A.
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p. 1028 - 1032
(2007/10/02)
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