- Visible-light photoredox-catalyzed selective carboxylation of C(sp3)?F bonds with CO2
-
It is highly attractive and challenging to utilize carbon dioxide (CO2), because of its inertness, as a nontoxic and sustainable C1 source in the synthesis of valuable compounds. Here, we report a novel selective carboxylation of C(sp3)?F bonds with CO2 via visible-light photoredox catalysis. A variety of mono-, di-, and trifluoroalkylarenes as well as α,α-difluorocarboxylic esters and amides undergo such reactions to give important aryl acetic acids and α-fluorocarboxylic acids, including several drugs and analogs, under mild conditions. Notably, mechanistic studies and DFT calculations demonstrate the dual role of CO2 as an electron carrier and electrophile during this transformation. The fluorinated substrates would undergo single-electron reduction by electron-rich CO2 radical anions, which are generated in situ from CO2 via sequential hydride-transfer reduction and hydrogen-atom-transfer processes. We anticipate our finding to be a starting point for more challenging CO2 utilization with inert substrates, including lignin and other biomass.
- Bo, Zhi-Yu,Chen, Lin,Gao, Tian-Yu,Jing, Ke,Lan, Yu,Liu, Shi-Han,Luo, Shu-Ping,Yan, Si-Shun,Yu, Bo,Yu, Da-Gang
-
supporting information
p. 3099 - 3113
(2021/11/16)
-
- Aerobic epoxidation of styrene over Zr-based metal-organic framework encapsulated transition metal substituted phosphomolybdic acid
-
Catalytic epoxidation of styrene with molecular oxygen is regarded as an eco-friendly alternative to producing industrially important chemical of styrene oxide (STO). Recent efforts have been focused on developing highly active and stable heterogeneous catalysts with high STO selectivity for the aerobic epoxidation of styrene. Herein, a series of transition metal monosubstituted heteropolyacid compounds (TM-HPAs), such as Fe, Co, Ni or Cu-monosubstituted HPA, were encapsulated in UiO-66 frameworks (denoted as TM-HPA@UiO-66) by direct solvothermal method, and their catalytic properties were investigated for the aerobic epoxidation of styrene with aldehydes as co-reductants. Among them, Co-HPA@UiO-66 showed relatively high catalytic activity, stability and epoxidation selectivity at very mild conditions (313 K, ambient pressure), that can achieve 82 % selectivity to STO under a styrene conversion of 96 % with air as oxidant and pivalaldehyde (PIA) as co-reductant. In addition, the hybrid composite catalyst can also efficiently catalyze the aerobic epoxidation of a variety of styrene derivatives. The monosubstituted Co atoms in Co-HPA@UiO-66 are the main active sites for the aerobic epoxidation of styrene with O2/PIA, which can efficiently converting styrene to the corresponding epoxide through the activation of the in-situ generated acylperoxy radical intermediate.
- Hu, Dianwen,Song, Xiaojing,Zhang, Hao,Chang, Xinyu,Zhao, Chen,Jia, Mingjun
-
-
- Pd(OH)2/C, a Practical and Efficient Catalyst for the Carboxylation of Benzylic Bromides with Carbon Monoxide
-
A simple, efficient, cheap, and broadly applicable system for the carboxylation of benzylic bromides with carbon monoxide and water is reported. Upon simple reaction with only 2.5 wt % of Pearlman's catalyst and 10 mol % of tetrabutylammonium bromide in tetrahydrofuran at 110 °C for 4 h, a range of benzylic bromides can be smoothly converted to the corresponding arylacetic acids in good to excellent yields after simple extraction and acid-base wash. The reaction was found to be broadly applicable, scalable, and could be successfully extended to the use of ex situ-generated carbon monoxide and applied to the synthesis of the nonsteroidal anti-inflammatory drug diclofenac.
- Wakuluk-Machado, Anne-Marie,Dewez, Damien F.,Baguia, Hajar,Imbratta, Miguel,Echeverria, Pierre-Georges,Evano, Gwilherm
-
p. 713 - 723
(2020/02/04)
-
- Resolution of Vaulted Biaryl Ligands via Borate Esters of Quinine and Quinidine
-
Given the sudden and unexplained rise in the cost of (+)- A nd (-)-sparteine, an alternative method for the resolution of vaulted biaryls has been developed. This method involves the reaction of a racemic vaulted biaryl ligand with one equivalent of BH3·SMe2 and one equivalent of either quinine or quinidine. A precipitate then forms from the resulting mixture of diastereomeric borates as a result of differential solubilities. Hydrolysis of the precipitate then liberates the (S)-ligand in the case of quinine and the (R)-ligand in the case of quinidine, both with >99% ee. This method has been applied to 16 different vaulted biaryl ligands, including 10 whose preparation is described here for the first time. In addition, proof of principle has been demonstrated for the dynamic thermodynamic resolution of the vaulted biaryl ligands with this method in combination with a nonchiral copper(II) complex that can racemize the ligand.
- Cagnon, Brian R.,Mohammadlou, Aliakbar,Wulff, William D.,Yin, Xiaopeng,Zheng, Li
-
p. 10432 - 10450
(2020/09/23)
-
- Oxidation of Alkynyl Boronates to Carboxylic Acids, Esters, and Amides
-
A general efficient protocol was developed for the synthesis of carboxylic acids, esters, and amides through oxidation of alkynyl boronates, generated directly from terminal alkynes. This protocol represents the first example of C(sp)?B bond oxidation. This approach displays a broad substrate scope, including aryl and alkyl alkynes, and exhibits excellent functional group tolerance. Water, primary and secondary alcohols, and amines are suitable nucleophiles for this transformation. Notably, amino acids and peptides can be used as nucleophiles, providing an efficient method for the synthesis and modification of peptides. The practicability of this methodology was further highlighted by the preparation of pharmaceutical molecules.
- Li, Chenchen,Li, Ruoling,Zhang, Bing,Zhao, Pei,Zhao, Wanxiang
-
supporting information
p. 10913 - 10917
(2020/05/25)
-
- Method for converting benzyl borate compounds into phenylacetic acid and derivatives thereof by carbon dioxide
-
The invention discloses a method for converting benzyl borate compounds into phenylacetic acid and derivatives thereof by carbon dioxide. The method comprises the steps: dissolving the benzyl borate compounds and an alkali in an organic solvent in the absence of a metal catalyst, introducing carbon dioxide into the reaction system, carrying out a reaction at the temperature of 50-150 DEG C for 3-72 hours, and acidifying to obtain phenylacetic acid or the derivatives thereof. The method is a green, simple and efficient method for synthesizing phenylacetic acid and the derivatives thereof, greenhouse gas carbon dioxide is used as a carbon source in the reaction, no transition metal catalyst is used, and the method is environmentally friendly, economical and high in efficiency.
- -
-
Paragraph 0032-0033
(2020/03/06)
-
- Preparation method of acid with different substituent groups
-
The invention discloses a preparation method of an acid with different substituent groups. A terminal alkyne is lithiated with n-butyllithium, and then reacts with isopropoxyboronic acid pinacol ester, hydrogen chloride is added to achieve quenching, then the obtained reaction product is oxidized by an oxidizing agent, and the oxidized reaction product is separated and purified to obtain the acid.The method of the invention has the advantages of simplicity in operation, one-pot process preparation, no metal catalysis, nontoxic reagents, greenness, environmental friendliness and high atomic utilization rate, and provides a novel and quick way for preparing the acid with different substituent groups; and the obtained acid is an important fine chemical product, and can be widely used in fields of medicines, pesticides, spices and other industries.
- -
-
Paragraph 0098-0102
(2019/10/23)
-
- Electrogenerated Sm(II)-Catalyzed CO2 Activation for Carboxylation of Benzyl Halides
-
Sm(II)-catalyzed carboxylation of benzyl halides is reported through the electrochemical reduction of CO2. The transformation proceeds under mild reaction conditions to afford the corresponding phenylacetic acids in good to excellent yields. This user-friendly and operationally simple protocol represents an alternative to traditional strategies, which usually proceeds through the C(sp3)-halide activation pathway.
- Bazzi, Sakna,Schulz, Emmanuelle,Mellah, Mohamed
-
supporting information
p. 10033 - 10037
(2019/12/24)
-
- Visible-Light-Driven External-Reductant-Free Cross-Electrophile Couplings of Tetraalkyl Ammonium Salts
-
Cross-electrophile couplings between two electrophiles are powerful and economic methods to generate C-C bonds in the presence of stoichiometric external reductants. Herein, we report a novel strategy to realize the first external-reductant-free cross-electrophile coupling via visible-light photoredox catalysis. A variety of tetraalkyl ammonium salts, bearing primary, secondary, and tertiary C-N bonds, undergo selective couplings with aldehydes/ketone and CO2. Notably, the in situ generated byproduct, trimethylamine, is efficiently utilized as the electron donor. Moreover, this protocol exhibits mild reaction conditions, low catalyst loading, broad substrate scope, good functional group tolerance, and facile scalability. Mechanistic studies indicate that benzyl radicals and anions might be generated as the key intermediates via photocatalysis, providing a new direction for cross-electrophile couplings.
- Liao, Li-Li,Cao, Guang-Mei,Ye, Jian-Heng,Sun, Guo-Quan,Zhou, Wen-Jun,Gui, Yong-Yuan,Yan, Si-Shun,Shen, Guo,Yu, Da-Gang
-
p. 17338 - 17342
(2019/01/04)
-
- A General, Activator-Free Palladium-Catalyzed Synthesis of Arylacetic and Benzoic Acids from Formic Acid
-
A new catalyst for the carboxylative synthesis of arylacetic and benzoic acids using formic acid (HCOOH) as the CO surrogate was developed. In an improvement over previous work, CO is generated in situ without the need for any additional activators. Key to success was the use of a specific system consisting of palladium acetate and 1,2-bis((tert-butyl(2-pyridinyl)phosphinyl)methyl)benzene. The generality of this method is demonstrated by the synthesis of more than 30 carboxylic acids, including non-steroidal anti-inflammatory drugs (NSAIDs), under mild conditions in good yields.
- Wang, Lin,Neumann, Helfried,Beller, Matthias
-
supporting information
p. 6910 - 6914
(2018/06/04)
-
- Synthetic method of fatty acid containing nitrogen heterocycle
-
The invention discloses a synthetic method of fatty acid containing nitrogen heterocycle. The synthetic method comprises the following steps: (S1) adding a heterocyclic compound with substitution of chloromethyl groups, a catalyst and a solvent DMF into a reaction kettle; (S2) introducing carbon dioxide to lead the pressure in the kettle to be 2-4MPa, adjusting and reacting for 10-16 hours at thetemperature of 40-50 DEG C; (S3) adding diluted hydrochloric acid into the reaction kettle to carry out acidification, using ethyl acetate for extraction, combining organic phases, carrying out rotaryevaporation to remove liquid, and further carrying out vacuum drying, thus obtaining the fatty acid containing nitrogen heterocycle. The synthetic method disclosed by the invention has the beneficialeffects that a one-pot method is adopted, the raw materials are easy to obtain, price is low, aftertreatment of products is also simpler, the universality for a substrate is also very high, and the promotion and application are easy.
- -
-
Paragraph 0042
(2018/07/30)
-
- Metal-free, catalytic regioselective oxidative conversion of vinylarenes: A mild approach to phenylacetic acid derivatives
-
A new synthetic approach towards the synthesis of phenylacetic acids from aromatic alkenes has been developed for the first time under mild conditions by employing non-toxic reagents such as molecular iodine and oxone. This metal-free catalytic regioselective oxygenation of vinylarenes proceeds via tandem iodofunctionalization/de-iodination induced rearrangement.
- Kodumuri, Srujana,Peraka, Swamy,Mameda, Naresh,Chevella, Durgaiah,Banothu, Rammurthy,Nama, Narender
-
p. 6719 - 6723
(2016/02/03)
-
- Dual stereocontrol in aldol reactions catalysed by hydroxyproline derivatives in the presence of a large amount of water
-
Parameters influencing dual stereocontrol in aldol reactions of water miscible acetone with aromatic aldehydes in the presence of a large amount of water using hydroxyproline based catalysts were studied. Stereocontrol was achieved by changing the acidity and basicity of the reaction media by the addition of achiral salts in the presence of a single chiral catalyst. Under acidic conditions (NH4Cl salt) the (R)-aldol product was formed in excess while basic aqueous media (carboxylate salts) led to the enrichment of the (S)-enantiomer. Reaction conditions under which the reaction is feasible were optimised and the effect of the structure of the hydroxyproline-based catalysts was investigated. The results show that the formation of a biphasic micellar system and the presence of an appropriate catalyst are both crucial for the reaction to occur. Although the catalyst structure influenced the formation and stabilisation of the micellar system to a large extent, its effect on the enantioselectivities were found to be less pronounced.
- Gurka, András A.,Sz?ri, Kornél,Bartók, Mihály,London, Gábor
-
supporting information
p. 936 - 942
(2016/09/13)
-
- Nickel-Catalyzed Carboxylation of Benzylic C-N Bonds with CO2
-
A user-friendly Ni-catalyzed reductive carboxylation of benzylic C-N bonds with CO2 is described. This procedure outperforms state-of-the-art techniques for the carboxylation of benzyl electrophiles by avoiding commonly observed parasitic pathways, such as homodimerization or β-hydride elimination, thus leading to new knowledge in cross-electrophile reactions.
- Moragas, Toni,Gaydou, Morgane,Martin, Ruben
-
supporting information
p. 5053 - 5057
(2016/04/26)
-
- Palladium-Catalyzed Carboxylation of Benzyl Chlorides with Atmospheric Carbon Dioxide in Combination with Manganese/Magnesium Chloride
-
An efficient direct carboxylation of a series of benzyl chlorides with CO2 catalyzed by Pd(OAc)2/dicyclohexyl (2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (SPhos) was developed to afford the corresponding phenylacetic acids in combination with Mn powder as a reducing reagent and MgCl2 as an indispensable additive. The reaction proceeded smoothly under 1 atm CO2. The application of Mn powder instead of a sensitive reducing reagent represents an operationally simple access to phenylacetic acids. Notably, MgCl2 is able to stabilize the (SPhos)2PdII(Bn)(Cl)(η1-CO2)(MgCl2) adduct and thus facilitates CO2 insertion into the PdII-C bond, which is supported by a DFT study. Specific effect: MgCl2 facilitates the direct insertion of CO2 into the PdII-C bond by stabilizing the PdII-CO2 adduct. With MgCl2 as an indispensable additive, the Pd-catalyzed carboxylation of various benzyl chlorides proceeded smoothly under 1 atm CO2, and the application of Mn powder instead of a sensitive reducing reagent makes this protocol an operationally simple access to phenylacetic acids.
- Zhang, Shuai,Chen, Wei-Qiang,Yu, Ao,He, Liang-Nian
-
p. 3972 - 3977
(2016/01/26)
-
- NITROGEN-CONTAINING CONDENSED HETEROCYCLIC COMPOUND
-
There are provided compounds represented by the following general formula (I) or pharmaceutically acceptable salts of thereof, which have a superior monoacylglycerol acyltransferase 2 inhibitory action: wherein Ring A represents a partially saturated heteroaryl group, an aryl group or a heteroaryl group, RB represents a C4-18 alkyl group, a C3-8 cycloalkyl group, a partially saturated aryl group, an aryl group, or the following formula (II): wherein V represents the formula -CR11R12-, -CO-, -CO-O-, or -CO-NH-, W represents a single bond or a C1-3 alkylene group, and Ring B represents a C3-8 cycloalkyl group, a C3-8 cycloalkenyl group, a partially saturated heteroaryl group, a saturated heterocyclyl group, an aryl group, or a heteroaryl group, Y represents a nitrogen atom or the formula N+(RF), RF represents a C1-4 alkyl group, and m and n, which may be the same or different, each represent an integer of 0 or 1.
- -
-
Paragraph 0283
(2014/02/15)
-
- Oxidative degradation of fragrant aldehydes. Autoxidation by molecular oxygen
-
The oxidative degradation of fragrant aldehydes by molecular oxygen has been investigated. The oxygen consumption was monitored and the bond dissociation energy (BDE) of the aldehyde C(O)-H bond were calculated by DFT method. The oxidation products were identified by GC/MS. The different pathways accounting for the oxidative degradation are discussed. The main product is the acid, beside the formate ester. Both oxidation products result from the Baeyer-Villiger reaction involving a peracid R(CO)OOH whereas minor products arise from the hydroperoxide ROOH intermediate derived either from the acyl peroxy radical, R(CO)OO or from the decarboxylation of the peracid RC(O)OOH.
- Marteau,Ruyffelaere,Aubry,Penverne,Favier,Nardello-Rataj
-
p. 2268 - 2275
(2013/04/10)
-
- Vaulted biaryls in catalysis: A structure-activity relationship guided tour of the immanent domain of the VANOL ligand
-
The active site in the BOROX catalyst is a chiral polyborate anion (boroxinate) that is assembled in situ from three equivalents of B(OPh) 3 and one of the VANOL ligand by a molecule of substrate. The substrates are bound to the boroxinate by Hbonds to oxygen atoms O1-O3. The effects of introducing substituents at each position of the naphthalene core of the VANOL ligand are systematically investigated in an aziridination reaction. Substituents in the 4,4′- and 8,8′-positions have a negative effect on catalyst performance, whereas, substituents in the 7- and 7′-positions have the biggest impact in a positive direction. VANOL destination: The active site in the BOROX catalyst is a chiral polyborate anion (boroxinate; see figure) that is assembled in situ from three equivalents of B(OPh)3 and one of the VANOL ligand by a molecule of substrate. The effects of introducing substituents at each position of the naphthalene core of the VANOL ligand are systematically investigated in an aziridination reaction. Copyright
- Guan, Yong,Ding, Zhensheng,Wulff, William D.
-
supporting information
p. 15565 - 15571
(2013/11/19)
-
- Ni-catalyzed direct carboxylation of benzyl halides with CO2
-
A novel Ni-catalyzed carboxylation of benzyl halides with CO2 has been developed. The described carboxylation reaction proceeds under mild conditions (atmospheric CO2 pressure) at room temperature. Unlike other routes for similar means, our method does not require well-defined and sensitive organometallic reagents and thus is a user-friendly and operationally simple protocol for assembling phenylacetic acids.
- León, Thierry,Correa, Arkaitz,Martin, Ruben
-
supporting information
p. 1221 - 1224
(2013/03/14)
-
- A new phenylalanine derivative acts as an antagonist at the AMPA Receptor GluA2 and introduces partial domain closure: Synthesis, resolution, pharmacology, and crystal structure
-
In order to map out molecular determinants for competitive blockade of AMPA receptor subtypes, a series of 2-carboxyethylphenylalanine derivatives has been synthesized and pharmacologically characterized in vitro. One compound in this series, (RS)-3h, showed micromolar affinity for GluA1o and GluA2(R)o receptors with an approximately 4-fold preference for GluA1/2 vs GluA3/4. In TEVC electrophysiological experiments (RS)-3h competitively antagonized GluA2(Q)i receptors. The X-ray structure of the active enantiomer (S)-3h in complex with GluA2-S1S2J showed a domain closure around 8°. Even though the nitro and the carboxyethyl groups of (S)-3h were both anchored to Tyr702 through a water H-bond network, these interactions only induced weak subtype selectivity. In spite of the fact that (S)-3h induced a domain closure close to that observed for partial agonists, it did not produce agonist responses at GluA2 receptors under nondesensitizing conditions. 2-Carboxyethylphenylalanine derivatives provide a new synthetic scaffold for the introduction of substituents that could lead to AMPA receptor subtype-selective ligands.
- Szymańska, Ewa,Frydenvang, Karla,Contreras-Sanz, Alberto,Pickering, Darryl S.,Frola, Elena,Serafimoska, Zorica,Nielsen, Birgitte,Kastrup, Jette S.,Johansen, Tommy N.
-
supporting information; experimental part
p. 7289 - 7298
(2011/12/04)
-
- Electrochemical carboxylation of benzylic carbonates: Alternative method for efficient synthesis of arylacetic acids
-
Electrochemical carboxylation of benzylic carbonates was successfully performed as an alternative method for the synthesis of phenylacetic acids by using a one-compartment cell equipped with a Pt plate cathode and an Mg rod anode in CH3CN to afford the corresponding phenylacetic acids in good yields.
- Ohkoshi, Masashi,Michinishi, Jun-Ya,Hara, Shoji,Senboku, Hisanori
-
experimental part
p. 7732 - 7737
(2010/10/21)
-
- Unified oxidation protocol for the synthesis of carbonyl compounds using a manganese catalyst
-
We have developed a unified protocol for the oxidation of ethers, benzylic compounds, and alcohols to carbonyl compounds. The protocol uses catalytic amounts of manganese(II) chloride tetrahydrate and tri(t-butyl)-2,2':6',2Prime;- terpyridine in combination with a stoichiometric amount of either m-chloroperbenzoic acid (MCPBA) or potassium hydrogen peroxysulfate (KHSO 5). A reagent system consisting of the Mn catalyst and MCPBA permitted the chemoselective sp3 C-H oxidation of alkyl ethers and benzylic compounds to generate the corresponding ketones. Alternatively, the water-soluble inorganic salt KHSO5 in combination with the Mn catalyst was used to oxidize alcohols to ketones or carboxylic acids. Importantly, the Mn catalyst/KHSO5 system eliminates technical difficulties associated with the isolation of carboxylic acid products. All the oxidations presented in this feature article proceed at sup-ambient temperature in an aerobic atmosphere, and can therefore be used in practical syntheses of complex organic molecules. Georg Thieme Verlag Stuttgart · New York.
- Kamijo, Shin,Amaoka, Yuuki,Inoue, Masayuki
-
experimental part
p. 2475 - 2489
(2010/09/06)
-
- Discovery and characterization of the N-phenyl-N′-naphthylurea class of p38 kinase inhibitors
-
An effort aimed at exploring structural diversity in the N-pyrazole-N′-naphthylurea class of p38 kinase inhibitors led to the synthesis and characterization of N-phenyl-N′-naphthylureas. Examples of these compounds displayed excellent inhibition of TNF-α production in vitro, as well as efficacy in a mouse model of lipopolysaccharide induced endotoxemia. In addition, perspective is provided on the role of a sulfonamide functionality in defining inhibitor potency.
- Cirillo, Pier F.,Hickey, Eugene R.,Moss, Neil,Breitfelder, Steffen,Betageri, Raj,Fadra, Tazmeen,Gaenzler, Faith,Gilmore, Thomas,Goldberg, Daniel R.,Kamhi, Victor,Kirrane, Thomas,Kroe, Rachel R.,Madwed, Jeffrey,Moriak, Monica,Netherton, Matthew,Pargellis, Christopher A.,Patel, Usha R.,Qian, Kevin C.,Sharma, Rajiv,Sun, Sanxing,Swinamer, Alan,Torcellini, Carol,Takahashi, Hidenori,Tsang, Michele,Xiong, Zhaoming
-
scheme or table
p. 2386 - 2391
(2009/12/07)
-
- Exceptionally simple catalytic system for the carbonylation of benzyl halides
-
A ligand-less catalytic system, Pd(OAc)2 immobilized in NBu4Hal melt is suggested for the synthesis of arylacetic acids by the carbonylation of benzyl bromides.
- Lapidus, Albert L.,Eliseev, Oleg L.,Bondarenko, Tatyana N.,Chau, Nguen H.,Kazantsev, Ruslan V.
-
scheme or table
p. 256 - 257
(2010/01/18)
-
- Oxidation of unsaturated compounds in ionic liquids with the use of cyclodextrin-containing catalytic systems
-
The Wacker oxidation of alkenes-1 in ionic liquids catalyzed by a system containing palladium, and copper complexes and β-cyclodextrins was studied. It was shown that the use of β-cyclodextrins substantially increases the oxidation rate in biphasic systems olefin/ionic liquid. It was found that the proposed catalytic systems possess substrate selectivity, which is determined by the structure of a receptor molecule.
- Andreeva,Maksimov,Zhuchkova,Predeina,Filippova,Karakhanov
-
p. 331 - 336
(2008/09/21)
-
- Analysis of structure-activity relationships for the 'B-region' of N-(4-t-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]-thiourea analogues as TRPV1 antagonists
-
The structure-activity relationships for the 'B-region' of N-(4-t-butylbenzyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. A docking model of potent antagonist 2 with the sensor region of TRPV1 is proposed.
- Lee, Jeewoo,Jin, Mi-Kyoung,Kang, Sang-Uk,Su, Yeon Kim,Lee, Jiyoun,Shin, Myoungyoup,Hwang, Jaemin,Cho, Sookhyun,Choi, Yeon-Sil,Choi, Hyun-Kyung,Kim, Sung-Eun,Suh, Young-Ger,Lee, Yong-Sil,Kim, Young-Ho,Ha, Hee-Jin,Toth, Attila,Pearce, Larry V.,Tran, Richard,Szabo, Tamas,Welter, Jacqueline D.,Lundberg, Daniel J.,Wang, Yun,Lazar, Jozsef,Pavlyukovets, Vladimir A.,Morgan, Matthew A.,Blumberg, Peter M.
-
p. 4143 - 4150
(2007/10/03)
-
- Biaryl amide glucagon receptor antagonists
-
Biaryl amides derived from a reported series of ureas 1 were evaluated and found to be potent human glucagon receptor antagonists. The benzofuran analogue 6i was administered in Sprague-Dawley rats and blocked the effects of an exogenous glucagon challenge.
- Kurukulasuriya, Ravi,Sorensen, Bryan K.,Link, James T.,Patel, Jyoti R.,Jae, Hwan-Soo,Winn, Marty X.,Rohde, Jeffrey R.,Grihalde, Nelson D.,Lin, Chun W.,Ogiela, Christopher A.,Adler, Andrew L.,Collins, Christine A.
-
p. 2047 - 2050
(2007/10/03)
-
- QUINOLINE-DERIVED AMIDE MODULATORS OF VANILLOID VR1 RECEPTOR
-
This invention is directed to vanilloid receptor VR1 ligands. More particularly, this invention relates to quinoline-derived amides that are potent antagonists or agonists of VR1 which are useful for the treatment and prevention of inflammatory and other pain conditions in mammals.
- -
-
-
- Compounds useful as anti-inflammatory agents
-
Disclosed are novel aromatic compounds of the formula (I) wherein G, X, Ar, L and Q are defined herein. The compounds are useful in pharmaceutic compositions for treating diseases or pathological conditions involving inflammation such as chronic inflammatory diseases. Also disclosed are processes of making such compounds.
- -
-
-
- Quinolones as gonadotropin releasing hormone (GnRH) antagonists: Simultaneous optimization of the C(3)-aryl and C(6)-substituents
-
A series of 3-arylquinolones was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. A variety of substitution patterns of the 3-aryl substituent are described. The 3,4,5-trimethylphenyl substituent (23h) was found to be optimal. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Young, Jonathan R.,Huang, Song X.,Chen, Irene,Walsh, Thomas F.,DeVita, Robert J.,Wyvratt Jr., Matthew J.,Goulet, Mark T.,Ren, Ning,Lo, Jane,Yang, Yi Tien,Yudkovitz, Joel B.,Cheng, Kang,Smith, Roy G.
-
p. 1723 - 1727
(2007/10/03)
-
- Synthesis of phenylacetic acids under rhodium-catalyzed carbonylation conditions
-
Benzyl halides are efficiently carbonylated to phenylacetic acids in the presence of a catalytic amount of the dimer of chloro(1,5-cyclooctadiene)rhodium(I) in formic acid. Under these reaction conditions, sensitive functionalities such as esters and nitriles are tolerated and the phenylacetic acids are obtained in good to high yields. (C) 2000 Elsevier Science Ltd.
- Giroux,Nadeau,Han
-
p. 7601 - 7604
(2007/10/03)
-
- Dendrimer poly(ethylenimine)s linked to β-cyclodextrin
-
β-Cyclodextrin was attached to two dendrimer poly(ethylenimine)s. The resulting cyclodextrin-containing dendrimers, CD-I and CD-II, can be considered either as dendrimers equipped with specific binding sites or as cyclodextrins containing amino groups around the cavities. Amines of CD-I and CD-II remarkably resisted protonation compared with those of the parent dendrimers. A compact conformation of CD-I or CD-II in which the dendrimer wraps itself around the cyclodextrin is proposed as a conformation consistent with the suppressed protonation. Esters containing t-butylphenyl groups were complexed by CD-I and CD-II and underwent fast deacylation. Kinetic data were obtained with several ester substrates, which revealed that two amino groups located in the vicinity of each cyclodextrin cavity of CD-I or CD-II participated as nucleophiles. In addition, optimum reactivity was attained when the spacer connecting the t-butylphenyl and the ester groups was -O- CH2- or -CH=CH-. Structures of the active sites for the accelerated deacylation of esters were elucidated on the basis of the kinetic data.
- Suh, Junghun,Hah, Sang Soo,Lee, Sang Hee
-
-
- Insecticidal quinazoline derivatives with (trifluoromethyl)diazirinyl and azido substituents as NADH:ubiquinone oxidoreductase inhibitors and candidate photoaffinity probes
-
Two candidate photoaffinity probes are designed from 4-substituted quinazolines known to be potent insecticides/acaricides and NADH:ubiquinone oxidoreductase inhibitors acting at or near the rotenone site. 4-(11- Azidoundecyl-2-amino)quinazoline, based on the undecylamino analog SAN 548A as a prototype, was synthesized in 18% overall yield from ethyl 10- undecenoate by oxidation of the terminal double bond, reductive amination, coupling to 4-chloroquinazoline, and functional group manipulation of the terminal ethyl ester to an alcohol, a mesylate and finally nucleophilic displacement with azide ions. 4-(4-(3-(Trifluoromethyl)-3H-diazirin-3- yl)phenethoxy)quinazoline [the (trifluoromethyl)diazirinyl analog of fenazaquin insecticide/acaricide] was prepared from 4-bromophenethyl alcohol in 31% overall yield by first introducing the trifluoromethylketone moiety followed by its conversion to the (trifluoromethyl)-diazirine and finally coupling to 4-chloroquinazoline as above. Both candidate photoaffinity probes have the inhibitory potency of rotenone (IC50 of 3-4 nM in each case). The azidoundecylamino compound has inadequate photoreactivity whereas that of the (trifluoromethyl)diazirinyl analog is ideal at 350 nm. Radiosynthesis of the latter photoaffinity ligand included introduction of the diazirinyl moiety as the carbene precursor, oxidation of (trifluoromethyl)diazirinylphenethyl alcohol to the corresponding acid with Jones' reagent, and reduction of the phenacetyl chloride intermediate with sodium borotritide to incorporate tritium.
- Latli, Bachir,Wood, Edgardo,Casida, John E.
-
p. 445 - 450
(2007/10/03)
-
- Pyridinium N-Phenoxide Betaines and their Application for the Characterization of Solvent Polarities, X.- Extension, Correction, and New Definition of the ET Solvent Polarity Scale by Application of a Lipophilic Penta-tert-butyl-substituted Pyridinium N-Phenoxide Betain Dye
-
The synthesis of the negatively solvatochromic, lipophilic penta-tert-butyl-substituted betaine dye 1d and the linear correlation between Z and ET(30) values permit a considerable enlargement of the ET(30) solvent polarity scale, the conversion of which into the dimensionless ENT scale is proposed .The ENT values for 243 solvents are compiled in Table 3.
- Reichardt, Christian,Harbusch-Goernert, Erwin
-
p. 721 - 743
(2007/10/02)
-
- Micellar Systems as ''Supercages'' for Reactions of Geminate Radical Pairs. Magnetic Effects
-
The photochemistry of dibenzyl ketone (DBK) and other molecules capable of producing benzyl radicals and substituted benzyl radicals has been investigated in micellar systems.The cage effect (percent of unscavengeable radical pairs produced by photolysis) was measured under a variety of conditions, and the results are compared with those obtained in homogeneous organic solvents.For example, parameters such as mean occupancy of ketone, detergent type and concentration, O2 concentration, additives, temperature, applied magnetic field, and pressure have been varied and investigated as to their influence on the magnitude of cage effect.In addition to modifying its environment, structural modification of the DBK by incorporation of 2H and 13C isotopes, hydrophobic groups, and heavy atoms was performed to investigate the impact of these variations on the cage effect in micellar systems.Isotopic substitution of 2H or 13C leads to results on both the quantum yields for reactions and on the percent cage that were consistent with expectations of magnetic isotope effects.Hydrophobic groups substituted in the 4-position of DBK were found to cause a substantial increase in the cage effect and yet retain the magnetic-field-dependent character found in the parent DBK.Incorporation of Br in the 4-position of DBK was found to enhance the cage effect but at the same time cause the cage effect to become magnetic field independent.Substitution of α-naphthyl for phenyl in DBK also produced magnetic-field-independent behavior, in addition to a dramatic decrease in the efficiency of photolysis.
- Turro, Nicholas J.,Weed, Gregory C.
-
p. 1861 - 1868
(2007/10/02)
-