- Small Molecule Inhibitors of the Bacterioferritin (BfrB)-Ferredoxin (Bfd) Complex Kill Biofilm-Embedded Pseudomonas aeruginosa Cells
-
Bacteria depend on a well-regulated iron homeostasis to survive adverse environments. A key component of the iron homeostasis machinery is the compartmentalization of Fe3+ in bacterioferritin and its subsequent mobilization as Fe2+ to satisfy metabolic requirements. In Pseudomonas aeruginosa Fe3+ is compartmentalized in bacterioferritin (BfrB), and its mobilization to the cytosol requires binding of a ferredoxin (Bfd) to reduce the stored Fe3+ and release the soluble Fe2+. Blocking the BfrB-Bfd complex in P. aeruginosa by deletion of the bfd gene triggers an irreversible accumulation of Fe3+ in BfrB, concomitant cytosolic iron deficiency and significant impairment of biofilm development. Herein we report that small molecules developed to bind BfrB at the Bfd binding site block the BfrB-Bfd complex, inhibit the mobilization of iron from BfrB in P. aeruginosa cells, elicit a bacteriostatic effect on planktonic cells, and are bactericidal to cells embedded in mature biofilms.
- Soldano, Anabel,Yao, Huili,Punchi Hewage, Achala N. D.,Meraz, Kevin,Annor-Gyamfi, Joel K.,Bunce, Richard A.,Battaile, Kevin P.,Lovell, Scott,Rivera, Mario
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p. 123 - 140
(2020/12/21)
-
- DMAP Mediated Efficient Construction of Functionalized Chromenes through One-Pot Reaction of para-Quinone Methides with Allenoates
-
A novel DMAP-mediated Rauhut-Currier/oxa-Michael addition cascade reaction of hydroxylphenyl-substituted para-quinone methide with allenoate was reported for the first time. A series of functionalized chromenes were successfully obtained with moderate to
- Song, Zefeng,Jia, Yuping,Zhang, Daizhou,Wang, De
-
supporting information
p. 1942 - 1948
(2021/04/05)
-
- NFSI/KF mediated mild and chemoselective interconversion of aryl TBDMS ethers to their benzene sulfonate
-
A one pot protocol for the transformation of aryl TBDMS ethers to corresponding benzene sulfonate esters using NFSI (N-flurobenzenesulfonimide)/KF is described. In situ generation of benzenesulfonyl fluoride directs chemoselective cleavage of aryl silyl ethers over alkyl silyl ethers. Electron withdrawing substituent's on aryl ring provided better yield than donating groups. Protecting groups and sensitive functionalities are well tolerated in this methodology. Thus, commercially available inexpensive reagents, mild reaction conditions and step economy are the advantages of this method.
- Dond, Bharat D.,Thore, Shivaji N.
-
supporting information
(2020/02/06)
-
- Enantioselective Construction of Spiro[chroman-thiazolones]: Bifunctional Phosphonium Salt-Catalyzed [2+4] Annulation between 5-Alkenyl Thiazolones and ortho-Hydroxyphenyl-Substituted para-Quinone Methides
-
The enantioselective formal [2+4] annulation of 5-alkenyl thiazolones with hydroxyl-substituted para-quinone methides was disclosed by dipeptide-based phosphonium salt catalysts. A wide range of functionalized spiro-chroman-thiazolone molecules bearing three contiguous 3° and/or 4° stereocenters were readily constructed in high yields with excellent stereoselectivities (>20:1 dr and up to >99.9% ee) under low catalyst loading and mild reaction conditions. The practicality and utility of this protocol were demonstrated by the scaled-up preparation and elaborations of product. (Figure presented.).
- Tan, Jian-Ping,Zhang, Hongkui,Jiang, Zhiyu,Chen, Yuan,Ren, Xiaoyu,Jiang, Chunhui,Wang, Tianli
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supporting information
p. 1058 - 1063
(2020/01/02)
-
- Enantioselective Catalytic [4+1]-Cyclization of ortho-Hydroxy-para-Quinone Methides with Allenoates
-
The first highly asymmetric catalytic synthesis of densely functionalized dihydrobenzofurans is reported, which starts from ortho-hydroxy-containing para-quinone methides. The reaction relies on an unprecedented formal [4+1]-annulation of these quinone methides with allenoates in the presence of a commercially available chiral phosphine catalyst. The chiral dihydrobenzofurans were obtained as single diastereomers in yields up to 90 % and with enantiomeric ratios up to 95:5.
- Zielke, Katharina,Ková?, Ond?ej,Winter, Michael,Pospí?il, Ji?í,Waser, Mario
-
supporting information
p. 8163 - 8168
(2019/06/04)
-
- Bifunctional Phosphonium Salt Directed Enantioselective Formal [4 + 1] Annulation of Hydroxyl-Substituted para-Quinone Methides with α-Halogenated Ketones
-
A highly diastereo- and enantioselective [4 + 1] cycloaddition of para-quinone methides to α-halogenated ketones was realized by bifunctional phosphonium salt catalysis, furnishing functionalized 2,3-dihydrobenzofurans in high yields and excellent stereoselectivities (>20:1 dr and up to >99.9% ee). Mechanistic observations suggested that the reaction underwent a cascade intermolecular substitution/intramolecular 1,6-addition process. DFT calculations revealed the presence of multiple H-bonding interactions between the catalyst and the enolate intermediate in the stereodetermining transition states.
- Tan, Jian-Ping,Yu, Peiyuan,Wu, Jia-Hong,Chen, Yuan,Pan, Jianke,Jiang, Chunhui,Ren, Xiaoyu,Zhang, Hong-Su,Wang, Tianli
-
supporting information
p. 7298 - 7302
(2019/10/02)
-
- PRODRUGS OF FUSED-BICYCLIC C5aR ANTAGONISTS
-
The present disclosure provides, inter alia, Compounds of Formulae IA, IB, IC, IIA, IIB and IIC or pharmaceutically acceptable salts thereof that are modulators of the C5a receptor. Also provided are pharmaceutical compositions and methods of use including the treatment of diseases or disorders involving pathologic activation from C5a and non-pharmaceutical applications.
- -
-
Paragraph 0262
(2019/10/23)
-
- Chemoselective Reduction of Sterically Demanding N,N-Diisopropylamides to Aldehydes
-
A sequential one-pot process for chemoselectively reducing sterically demanding N,N-diisopropylamides to aldehydes has been developed. In this reaction, amides are activated with EtOTf to form imidates, which are reduced with LiAlH(OR)3 [R = t-Bu, Et] to give aldehydes by hydrolysis of the resulting hemiaminals. The non-nucleophilic base 2,6-DTBMP remarkably improves reaction efficiency. The combination of EtOTf/2,6-DTBMP and LiAlH(O-t-Bu)3 was found to be optimal for reducing alkyl, alkenyl, alkynyl, and 2-monosubstituted aryl N,N-diisopropylamides. In contrast, EtOTf and LiAlH(OEt)3 in the absence of base were found to be optimal for reducing extremely sterically demanding 2,6-disubstituted N,N-diisopropylbenzamides. The reaction tolerates various reducible functional groups, including aldehyde and ketone. 1H NMR studies confirmed the formation of imidates stable in water. The synthetic usefulness of this methodology was demonstrated with N,N-diisopropylamide-directed ortho-metalation and C-H bond activation.
- Xiao, Peihong,Tang, Zhixing,Wang, Kai,Chen, Hua,Guo, Qianyou,Chu, Yang,Gao, Lu,Song, Zhenlei
-
p. 1687 - 1700
(2018/02/23)
-
- Gold-Catalyzed Oxidative Coupling of Alkynes toward the Synthesis of Cyclic Conjugated Diynes
-
Gold-catalyzed oxidative coupling of alkynes was developed as an efficient approach for the synthesis of challenging cyclic conjugated diynes (CCD). Compared with the classic copper-promoted oxidative coupling reaction of alkynes, this gold-catalyzed process exhibited a faster reaction rate due to rapid reductive elimination from the Au(III) intermediate. This unique reactivity thus allowed a challenging diyne macrocyclization to take place with high efficiency. Condition screening revealed an [(n-Bu)4N]+[Cl-Au-Cl]? salt as the optimal pre-catalyst. Macrocycles with ring size between 13 and 28 atoms were prepared in moderate to good yields, which highlighted the broad substrate scope of this new strategy. Furthermore, the synthetic utilities of the CCDs for copper-free click chemistry have been demonstrated, showcasing the potential application of this strategy in biological systems. Macrocycles are important structural moieties in medicinal and biological research, and efficient methods for macrocyclization are always in high demand. With the unique conformation having six carbon atoms in a linear geometry, the cyclic conjugated diynes (CCD) present greater synthetic challenges and have been much less explored. Therefore, application of these unique macrocycles in biological studies is largely unexplored. Here, we describe the discovery of gold-catalyzed Glaser-Hay type oxidative coupling of terminal alkynes to achieve CCD under diluted conditions with broad substrate scope and great functional group compatibility. Taking advantage of the 14-member cyclic diyne, a copper-free click chemistry was achieved, which provided an effective alternative strategy for the traditional cyclooctyne-based azide-alkyne cycloaddition, suggesting a promising future for this method in tackling challenging problems in related biological and medicinal research. Gold-catalyzed oxidative coupling of alkynes was developed as an efficient approach for the synthesis of challenging cyclic conjugated diyne. Compared with copper-promoted oxidative coupling, this protocol allowed macrocyclization under dilute conditions with good overall reactivity and high functional group tolerance. The success in achieving copper-free click chemistry on cyclic conjugated diyne highlights its potential application in biological and medicinal research.
- Ye, Xiaohan,Peng, Haihui,Wei, Chiyu,Yuan, Teng,Wojtas, Lukasz,Shi, Xiaodong
-
supporting information
p. 1983 - 1993
(2018/10/02)
-
- Vinylpyridines as Building Blocks for the Photocatalyzed Synthesis of Alkylpyridines
-
The photocatalyzed addition of several hydrogen donors (ethers, aldehydes, alkanes, amides) onto vinylpyridines was achieved. This approach provided access to alkylpyridines, which are important building blocks for the preparation of compounds with biological activity. The strategy was very simple and straightforward because it required only a small amount of a cheap decatungstate salt as photocatalyst. As an added advantage, the reaction could be performed under sunlight irradiation as well as under flow conditions.
- Capaldo, Luca,Fagnoni, Maurizio,Ravelli, Davide
-
supporting information
p. 6527 - 6530
(2017/05/15)
-
- Natural α-methylenelactam analogues: Design, synthesis and evaluation of α-alkenyl-γ and δ-lactams as potential antifungal agents against Colletotrichum orbiculare
-
In our continued efforts to improve the potential utility of the α-methylene-γ-lactone scaffold, 62 new and 59 known natural α-methylenelactam analogues including α-methylene-γ-lactams, α-arylidene-γ and δ-lactams, and 3-arylideneindolin-2-ones were synthesized as the bioisosteric analogues of the α-methylenelactone scaffold. The results of antifungal and cytotoxic activity indicated that among these derivatives compound (E)-1-(2, 6-dichlorobenzyl)-3-(2-fluorobenzylidene) pyrrolidin-2-one (Py51) possessed good selectivity with the highest antifungal activity against Colletotrichum orbiculare with IC50?=?10.4?μM but less cytotoxic activity with IC50?=?141.2?μM (against HepG2 cell line) and 161.2?μM (against human hepatic L02?cell line). Ultrastructural change studies performed by transmission electron microscope showed that Py51 could cause important cell morphological changes in C.?orbiculare, such as plasma membrane detached from cell wall, cell wall thickening, mitochondria disruption, a dramatic increase in vacuolation, and eventually a complete loss in the integrity of organelles. Significantly, mitochondria appeared one of the primary targets, as confirmed by their remarkably aberrant morphological changes. Analysis of structure–activity relationships revealed that incorporation of the aryl group into the α-exo-methylene and the N-benzyl substitution increased the activity. Meanwhile, the α-arylidene-γ-lactams have superiority in selectivity over the 3-arylideneindolin-2-ones. Based on the results, the N-benzyl substituted α-(2-fluorophenyl)-γ-lactam was identified as the most promising natural-based scaffold for further discovering and developing improved crop-protection agents.
- Delong, Wang,Lanying, Wang,Yongling, Wu,Shuang, Song,Juntao, Feng,Xing, Zhang
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p. 286 - 307
(2017/03/09)
-
- Ag/Br?nsted Acid Co-Catalyzed Spiroketalization of β-Alkynyl Ketones toward Spiro[chromane-2,1′-isochromene] Derivatives
-
A new Ag/Br?nsted acid co-catalyzed spiroketalization of β-alkynyl ketones with para-quinone methides (p-QMs) has been established, enabling multiple C-C and C-O bond-forming events to access densely functionalized spiro[chromane-2,1′-isochromene] derivat
- Liu, Shuai,Lan, Xin-Chan,Chen, Ke,Hao, Wen-Juan,Li, Guigen,Tu, Shu-Jiang,Jiang, Bo
-
supporting information
p. 3831 - 3834
(2017/07/26)
-
- Silver/Scandium-Cocatalyzed Bicyclization of β-Alkynyl Ketones Leading to Benzo[c]xanthenes and Naphtho[1,2-b]benzofurans
-
The combination of AgTFA and Sc(OTf)3 enables the bimetallic synergistic catalysis of β-alkynyl ketones and para-quinone methides (p-QMs), allowing direct synthesis of 17 examples of benzo[c]xanthenes with generally good yields through a benzannulation/1,6-addition/cyclization sequence. Exchanging p-QMs for quinone imine ketal resulted in 10 examples of tetracyclic naphtho[1,2-b]benzofurans via a similar benzannulation/1,4-addition/cyclization cascade. During these reaction processes, AgTFA and Sc(OTf)3 could be perfectly compatible, together with the realization of C(sp3)-H functionalization adjacent to carbonyl group on the β-alkynyl ketone unit.
- Chen, Ke,Liu, Shuai,Wang, Dan,Hao, Wen-Juan,Zhou, Peng,Tu, Shu-Jiang,Jiang, Bo
-
supporting information
p. 11524 - 11530
(2017/11/10)
-
- Tert-Butyldimethylsilyl Amine (TBDMS-NH2): A Mild and Green Reagent for the Protection of Benzyl Alcohols, Phenols, and Carboxylic Acids under Solvent-Free Conditions
-
Herein, we present the use of the tert-butyldimethylsilyl amine (TBDMS-NH2) as a silylating reagent for phenols, benzyl alcohols, and carboxylic acids. Unlike other silyl protection reactions, this reported process with TBDMS-NH2 does not involve the form
- Duczynski, Jeremy A.,Fuller, Rebecca,Stewart, Scott G.
-
p. 1172 - 1179
(2016/10/13)
-
- HETEROARYL COMPOUNDS USEFUL AS INHIBITORS OF SUMO ACTIVATING ENZYME
-
Disclosed are chemical entities which are compounds of formula (I); or pharmaceutically acceptable salts thereof; wherein Y, Ra, Ra', Rb, Rc, X1, X2, X3, Rd, Z1, and Z2 have the values described herein and stereochemical configurations depicted at asterisked positions indicate absolute stereochemistry. Chemical entities according to the disclosure can be useful as inhibitors of Sumo Activating Enzyme (SAE). Further provided are pharmaceutical compositions comprising a compound of the disclosure and methods of using the compositions in the treatment of proliferative, inflammatory, cardiovascular, and neurodegenerative diseases or disorders.
- -
-
Paragraph 00354
(2016/01/25)
-
- Michael additions of highly basic enolates to ortho -quinone methides
-
A protocol by which ketone or ester enolates and ortho-quinone methides (o-QMs) are generated in situ in a single reaction flask from silylated precursors under the action of anhydrous fluoride is reported. The reaction partners are joined to give a variety of β-(2-hydroxyphenyl)-carbonyl compounds in 32-94% yield in a single laboratory operation. The intermediacy of o-QMs is supported by control experiments utilizing enolate precursors and conventional alkyl halides as competitive alkylating agents and the isolation of 1,5-dicarbonyl products resulting from conjugate additions that do not restore the aromatic system.
- Lewis, Robert S.,Garza, Christopher J.,Dang, Ann T.,Pedro, Te Kie A.,Chain, William J.
-
supporting information
p. 2278 - 2281
(2015/05/13)
-
- Versatile CuI/Pd0 dual catalysis for the synthesis of quaternary α-allylated carbonyl compounds: Development, mechanistic investigations and scope
-
We report herein a versatile cooperative dual catalysis reaction based on a CuI/Pd0 system. Mechanistic investigation shows that every component plays a crucial role in determining the reaction outcome. The reaction is successfully extended to various substrates; such as α,β-unsaturated ketones, malonates and coumarins. The strategy tolerates different substitution patterns and affords good yields for each family of substrates.
- Nahra, Fady,Mace, Yohan,Boreux, Arnaud,Billard, Francois,Riant, Olivier
-
supporting information
p. 10970 - 10981
(2014/09/17)
-
- Practical asymmetric catalytic synthesis of spiroketals and chiral diphosphine ligands
-
A practical procedure has been developed for efficient synthesis of chiral aromatic spiroketals and the relevant diphosphine ligands. The procedure includes first asymmetric hydrogenation of readily available α, α'-bis(2-benzyloxyarylidene) ketones cat-al
- Wang, Xiaoming,Wang, Xubin,Guo, Peihua,Wang, Zheng,Ding, Kuiling
-
supporting information
p. 2900 - 2907
(2014/03/21)
-
- Enantioselective copper-catalyzed intramolecular phenolic O-H bond insertion: Synthesis of chiral 2-carboxy dihydrobenzofurans, dihydrobenzopyrans, and tetrahydrobenzooxepines
-
Efficient: A copper-catalyzed enantioselective intramolecular insertion of carbenoids into phenolic O-H bonds has been developed. This method can be used for the synthesis of the title compounds in high yields and excellent enantioselectivities under mild and neutral conditions (see scheme). NaBAr F=sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate. Copyright
- Song, Xiao-Guang,Zhu, Shou-Fei,Xie, Xiu-Lan,Zhou, Qi-Lin
-
supporting information
p. 2555 - 2558
(2013/04/10)
-
- Multidentate triphenolsilane-based alkyne metathesis catalysts
-
A series of triphenolsilane-coordinated molybdenum(VI) propylidyne catalysts has been developed, which are resistant to small alkyne polymerization and compatible with various functional groups (including phenol substrates). The catalysts remain active in
- Yang, Haishen,Liu, Zhenning,Zhang, Wei
-
supporting information
p. 885 - 890
(2013/05/08)
-
- Highly Active Multidentate Catalysts for Efficient Alkyne Metathesis
-
The invention relates to highly active and selective catalysts for alkyne metathesis. In one aspect, the invention includes a multidentate organic ligand wherein one substrate-binding site of the metal center is blocked. In another aspect, the invention includes N-quaternized or silane-based multidentate organic ligands, capable of binding to metals. In yet another aspect, the invention includes N-quaternized or silane-based multidentate catalysts. The catalysts of the invention show high robustness, strong resistance to small alkyne polymerization and significantly enhanced catalytic activity compared to their corresponding non-quaternized or non-silane-based multidentate catalyst analogues.
- -
-
Paragraph 0235
(2013/10/08)
-
- Mild and rapid method for the generation of ortho -(naphtho)quinone methide intermediates
-
A new mild method has been devised for generating o-(naphtho)quinone methides via fluoride-induced desilylation of silyl derivatives of o-hydroxybenzyl(or 1-naphthylmethyl) nitrate. The reactive o-(naphtho)quinone methide intermediates were trapped by C,
- Shaikh, Abdul Kadar,Cobb, Alexander J. A.,Varvounis, George
-
scheme or table
p. 584 - 587
(2012/03/10)
-
- A novel and efficient stereo-controlled synthesis of hexahydroquinolinones via the diene-transmissive hetero-Diels-Alder reaction of cross-conjugated azatrienes with ketenes and electrophilic dienophiles
-
The diene-transmissive hetero-Diels-Alder (DTHDA) reactions of cross-conjugated azatrienes (divinylimines or penta-1,4-dien-3-imines) having an N-aryl, N-alkyl, or N-dimethylamino substituent have been examined. The initial reaction of the azatrienes with diphenylketene at room temperature yielded β-lactams of [2+2] cycloadducts, which upon heating underwent [1,3]-sigmatropic rearrangement to produce the formal [4+2] cycloadducts. The reaction of N-phenylazatriene with dimethylketene or dichloroketene produced the [2+2] cycloadducts only, while the reaction of N-(dimethylamino)azatriene with dichloroketene gave the [4+2] cycloadduct without heating. When the [2+2] cycloadduct has two different vinyl substituents at C-4 of the β-lactam ring, the regioselectivity of the rearrangement depends on steric factors and the electronic demand of the substituents. The second Diels-Alder reaction of the initial [4+2] cycloadducts with electron-deficient dienophiles (TCNE, N-phenylmaleimide) stereoselectively yielded hexahydroquinolinone derivatives. Similarly, a tandem intermolecular-intramolecular mode of the aza-DTHDA reactions produced tetracyclic nitrogen-containing heterocycles in a regio- and stereoselective manner.
- Kobayashi, Satoru,Semba, Tomomi,Takahashi, Taku,Yoshida, Satoko,Dai, Kotaro,Otani, Takashi,Saito, Takao
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experimental part
p. 920 - 933
(2009/04/07)
-
- Synthesis of 6,6-bisbenzannulated spiroketals related to the rubromycins using a double intramolecular hetero-Michael addition (DIHMA)
-
The synthesis of a series of 6,6-bisbenzannulated spiroketals using a novel microwave-assisted DIHMA approach is reported. Coupling of an aryl acetylene and an aryl aldehyde via acetylide anion addition resulted in the formation of an alkynol which was followed by oxidation to the desired ynone. Spirocyclization using the DIHMA protocol afforded the desired bisbenzannulated spiroketal in good yield.
- Choi, Peter J.,Rathwell, Dominea C.K.,Brimble, Margaret A.
-
scheme or table
p. 3245 - 3248
(2009/08/17)
-
- A novel and facile stereocontrolled synthetic method for polyhydro-quinolines and pyridopyridazines via a diene-transmissive Diels-Alder reaction involving inverse electron-demand hetero Diels-Alder cycloaddition of cross-conjugated azatrienes
-
Cross-conjugated azatrienes bearing an electron-withdrawing sulfonyl or benzoyl group on the nitrogen atom underwent, on heating or in the presence of a Lewis acid (TMSOTf), an initial inverse electron-demand hetero Diels-Alder reaction with electron-rich dienophiles (vinyl ether, vinyl thioether, and allenyl ether) to produce 1:1 cycloadducts with high endo selectivity. The initial cycloadducts thus obtained underwent a second Diels-Alder reaction stereoselectively on the newly formed diene unit with electron-deficient dienophiles to give the crossed bis-cycloadducts, octahydroquinolines, with high diastereo-π-facial selectivity. The N-sulfonylazatrienes tethering an ortho-cinnamyloxyphenyl dienophile at the triene terminal underwent an initial intramolecular hetero Diels-Alder reaction of the inverse electron-demand type. The subsequent second Diels-Alder reaction of the formed mono-cycloadducts completed the diene-transmissive hetero Diels-Alder protocol to give benzopyrano[3,4-c]quinolines in a highly stereoselective manner.
- Kobayashi, Satoru,Furuya, Tomoki,Otani, Takashi,Saito, Takao
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p. 9705 - 9716
(2008/12/22)
-
- Controlling cis/trans-selectivity in intramolecular Diels-Alder reactions of benzo-tethered, ester linked 1,3,9-decatrienes
-
Predictions from DFT (B3LYP/6-31 G(d))-computed stereoisomer product distributions for intramolecular Diels-Alder (IMDA) reactions have been successfully replicated in the laboratory. Benzo-tethered hexadienyl acrylates generally undergo moderately trans-
- Pearson, Emma L.,Willis, Anthony C.,Sherburn, Michael S.,Paddon-Row, Michael N.
-
scheme or table
p. 513 - 522
(2008/10/09)
-
- Mild and rapid method for the generation of o-quinone methide intermediates. Synthesis of puupehedione analogues
-
A route to simpler analogues to bioactive puupehedione derivatives involving a hetero Diels-Alder cycloaddition of a o-quinone methide is described. These intermediate species are generated via fluoride-induced desilylation of silyl derivatives of o-hydro
- Barrero, Alejandro F.,Quílez del Moral, José F.,Mar Herrador,Arteaga, Pilar,Cortés, Manuel,Benites, Julio,Rosellón, Antonio
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p. 6012 - 6017
(2007/10/03)
-
- Structure-activity relationships of 1′S-1′-acetoxychavicol acetate for inhibitory effect on NO production in lipopolysaccharide-activated mouse peritoneal macrophages
-
1′S-1′-Acetoxychavicol acetate from the rhizomes of Alpinia galanga inhibited nitric oxide (NO) production in lipopolysaccharide-activated mouse peritoneal macrophages with an IC50 value of 2.3 μM. To clarify the structure-activity relationship of 1′S-1′- acetoxychavicol acetate, various natural and synthetic phenylpropanoids and synthetic phenylbutanoids were examined, and the following structural requirements were clarified. (1) The para or ortho substitution of the acetoxyl and 1-acetoxypropenyl groups at the benzene ring was essential. (2) The S configuration of the 1′-acetoxyl group was preferable. (3) The presence of the 3-methoxyl group and disappearance of the 2′-3′ double bond by hydrogenation reduced the activity. (4) The substitution of acetyl groups with propionyl or methyl groups reduced the activity. (5) Lengthening of the carbon chain between the 1′- and 2′-positions reduced the activity.
- Matsuda, Hisashi,Ando, Shin,Morikawa, Toshio,Kataoka, Shinya,Yoshikawa, Masayuki
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p. 1949 - 1953
(2007/10/03)
-
- Derivatives of dicarboxylic acid having pharmaceutical properties
-
The present invention relates to the compounds of the general formula (I) and their salts and stereoisomers for the production of medicaments for the treatment of cardiovascular disorders.
- -
-
Page/Page column 66-67
(2010/02/11)
-
- NOVEL DICARBOXYLIC ACID DERIVATIVES WITH PHARMACEUTICAL PROPERTIES
-
The present invention relates to the use of compounds of the formula (I) and to their salts and stereoisomers, for the preparation of medicaments for the treatment of cardiovascular disorders.
- -
-
Page/Page column 63
(2010/02/14)
-
- A new approach to 2,2-disubstituted chromenes and tetrahydroquinolines through intramolecular cyclization of chiral 3,4-epoxy alcohols
-
An efficient route to chiral chromene and tetrahydroquinoline ring models 3 and 4 was developed by means of the vanadium epoxidation of chiral homoallylic alcohols 12 and 19 followed by an intramolecular epoxide opening of 3,4-epoxy alcohols 14 and 20. Th
- Goujon, Jean-Yves,Zammattio, Fran?oise,Chrétien, Jean-Mathieu,Beaudet, Isabelle
-
p. 4037 - 4049
(2007/10/03)
-
- Nicotinamide derivatives and a tiotropium salt in combination for the treatment of diseases
-
The invention relates to a combination of a nicotinamide derivative and tiotropium or a derivative thereof, compositions containing it and the uses of, such a combination. The combination according to the present invention is useful in numerous diseases, disorders and conditions, in particular inflammatory, allergic and respiratory diseases, disorders and conditions.
- -
-
-
- A highly efficient procedure for regeneration of carbonyl groups from their corresponding oxathioacetals and dithioacetals using sodium nitrite and acetyl chloride in dichloromethane
-
A wide variety of oxathioacetals 1 as well as dithioacetals 2 can be chemoselectively deprotected to the corresponding carbonyl compounds 3 in good yields by employing NaNO2-AcCl and H2O in CH2Cl2 at 0°C to room temperature. Some of the major advantages of this procedure are: mild conditions, easy to handle, highly chemoselective and efficient, high yields and inexpensive reagents. In addition, no acetylation occurs at the hydroxyl group nor chlorination takes place at the double bond.
- Khan, Abu T.,Mondal, Ejabul,Sahu, Priti R.
-
p. 377 - 381
(2007/10/03)
-
- Synthesis of 2-(Diarylmethylene)-3-benzofuranones Promoted via Palladium-Catalyzed Reactions of Aryl iodides with 3-Aryl-1-(2-tert- butyldimethylsilyloxy)phenyl-2-propyn-1-ones
-
3-Substituted-1-(2-tert-butyldimethylsilyloxy)phenyl-2-propyn-1-ones were coupled with aryl iodides by using palladium as a catalyst in ambient MeOH solution and gave 2-(diarylmethylene)-3-benzofuranones in moderate to good yields.
- Lin, Chi-Fong,Lu, Wen-Der,Wang, I.-Wen,Wu, Ming-Jung
-
p. 2057 - 2061
(2007/10/03)
-
- Does the DABCO-catalysed reaction of 2-hydroxybenzaldehydes with methyl acrylate follow a Baylis-Hillman pathway?
-
Evidence is presented which supports the intermediacy of dipolar Baylis-Hillman-type adducts in the synthesis of coumarin and chromene derivatives from the reaction of 2-hydroxybenzaldehydes with methyl acrylate in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO).
- Kaye, Perry T.,Musa, Musiliyu A.,Nocanda, Xolani W.,Robinson, Ross S.
-
p. 1133 - 1138
(2007/10/03)
-
- A useful and environmentally benign synthetic protocol for dethiolization by employing vanadium pentoxide catalyzed oxidation of ammonium bromide by hydrogen peroxide
-
A wide variety of thioacetals and thioketals can be cleaved chemoselectively in presence of olefin and aromatic ring as well as other protecting groups to carbonyl compounds by employing V2O5 catalyzed oxidation of ammonium bromide by H2O2 in CH2Cl2-H2O solvent system; mild conditions, high selectivity, good yield, and no side products such as bromination or oxidation are some of the major advantages.
- Mondal, Ejabul,Bose, Gopal,Sahu, Priti Rani,Khan, Abu T.
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p. 1158 - 1159
(2007/10/03)
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- Oxidative cleavage of diethyldithioacetals by ammonium bromide promoted by (NH4)6Mo7O24.4H2O-H 2O2: A useful synthetic protocol for regeneration of carbonyl compounds
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Ammonium heptamolybdate promotes selective deprotection of a wide variety of diethyldithioacetals of aldehydes or ketones 1 into the parent carbonyl compounds 2, by ammonium bromide in presence of hydrogen peroxide and catalytic amount of perchloric acid at 0-5 °C in dichloromethane-water solvent system; mild conditions, high selectivity, good yield and easy work-up are some of the major advantages of the synthetic method.
- Khan,Boruwa,Mondal,Bose
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p. 1039 - 1042
(2007/10/03)
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- 6-Endo- and 5-exo-digonal cyclizations of o-hydroxyphenyl ethynyl ketones: A key step for highly selective benzopyranone formation
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The cyclization of o-hydroxyphenyl ethynyl ketones was examined from theoretical and experimental standpoints in order to develop efficient synthetic methods for the construction of 2-substituted pyranones possessing significant biological activities. Ab initio studies at HF/6-31G* level on the cyclization indicated that both 6-endo-digonal and 5-exo-digonal cyclizations giving benzopyranones and benzofuranones, respectively, were endothermic and reversible in aprotic media, and the irreversible protonation of the resulting unions would be critical for the products formation. We generated phenoxide ion under aprotic conditions in situ by desilylation of o-silyloxyphenyl ethynyl ketones with spray dried potassium fluoride and 18- crown-6 in anhydrous DMF. Under these conditions the cyclization of variety o-hydroxyphenyl ethynyl ketones proceeded smoothly to produce benzopyranone derivatives with exceedingly high selectivity. Theoretical and experimental results strongly suggested that the presence of a small amount of proton donor effecting the protonation of the resulting benzopyranone union was essential for the high 6-endo-diagonal selectivity.
- Nakatani, Kazuhiko,Okamoto, Akimitsu,Saito, Isao
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p. 9427 - 9446
(2007/10/03)
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- Intramolecular nucleophilic acyl substitution reaction of 3,4-alkadienyl carbonates mediated by Ti(O-i-Pr)4/2 i-PrMgCl reagent. Efficient synthesis of optically active β,γ-unsaturated esters with an α-substituent
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Treatment of 3,4-alkadienyl carbonates 2a-i with a low-valent titanium reagent diisopropoxy(η2-propene)titanium (1), readily generated by the reaction of Ti(O-i-Pr)4 with 2 i-PrMgCl, resulted in an intramolecular nucleophilic acyl substitution (INAS) reaction to afford vinyltitanium compounds 3 which, in turn, reacted with H3O+, D2O, or iodine to give α-substituted β,γ-unsaturated esters 4 in good to excellent yields. The olefin moiety of the hydrolysis product 4 has (Z)-geometry mainly except for 4h. Starting from chiral 2f or 2g, the reaction proceeded stereospecifically to give optically active α-substituted β,γ-unsaturated ester 4f or 4g having (Z)-olefin geometry exclusively.
- Yoshida, Yukio,Okamoto, Sentaro,Sato, Fumie
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p. 7826 - 7831
(2007/10/03)
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- Polymer-supported reactions in organic synthesis: Part 1 - Protection and deprotection of phenols using anion exchange resin.
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Phenoxide ions supported on Amberlite IRA-400 (chloride form) are protected as t-butyl(dimethyl)silyl (TBDMS) ethers in good to excellent yields and subsequently deprotected by fluoride ions supported on Amberlite IRA-400 (chloride form).
- Bandgar, B. P.,Unde, S. D.,Unde, D. S.,Kulkarni, V. H.,Patil, S. V.
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p. 782 - 784
(2007/10/03)
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- RHODIUM CARBENOID MEDIATED CYCLISATIONS. PART 2. SYNTHESIS OF CYCLIC ETHERS
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Alkylation of the dianion of methyl acetoacetate with the t-butyldimethylsilyl protected α,ω-halogeno alcohols (1)-(9) gives the β-keto esters (1) which are converted into the diazo alcohols (3) by diazo transfer and desilylation.Rhodium carbenoid cyclisa
- Heslin, Julie C.,Moody, Christopher J.
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p. 1417 - 1424
(2007/10/02)
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