- Photoredox Activation of Formate Salts: Hydrocarboxylation of Alkenes via Carboxyl Group Transfer
-
A photoredox activation mode of formate salts for carboxylation was developed. Using a formate salt as the reductant, carbonyl source, and hydrogen atom transfer reagent, a wide range of alkenes can be converted into acid products via a carboxyl group tra
- Huang, Yan,Hou, Jing,Zhan, Le-Wu,Zhang, Qian,Tang, Wan-Ying,Li, Bin-Dong
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p. 15004 - 15012
(2021/12/14)
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- Photoinduced Hydrocarboxylation via Thiol-Catalyzed Delivery of Formate across Activated Alkenes
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Herein we disclose a new photochemical process to prepare carboxylic acids from formate salts and alkenes. This redox-neutral hydrocarboxylation proceeds in high yields across diverse functionalized alkene substrates with excellent regioselectivity. This operationally simple procedure can be readily scaled in batch at low photocatalyst loading (0.01% photocatalyst). Furthermore, this new reaction can leverage commercially available formate carbon isotologues to enable the direct synthesis of isotopically labeled carboxylic acids. Mechanistic studies support the working model involving a thiol-catalyzed radical chain process wherein the atoms from formate are delivered across the alkene substrate via CO2?- as a key reactive intermediate.
- Alektiar, Sara N.,Wickens, Zachary K.
-
supporting information
p. 13022 - 13028
(2021/09/03)
-
- Exploration of New Biomass-Derived Solvents: Application to Carboxylation Reactions
-
A range of hitherto unexplored biomass-derived chemicals have been evaluated as new sustainable solvents for a large variety of CO2-based carboxylation reactions. Known biomass-derived solvents (biosolvents) are also included in the study and the results are compared with commonly used solvents for the reactions. Biosolvents can be efficiently applied in a variety of carboxylation reactions, such as Cu-catalyzed carboxylation of organoboranes and organoboronates, metal-catalyzed hydrocarboxylation, borocarboxylation, and other related reactions. For many of these reactions, the use of biosolvents provides comparable or better yields than the commonly used solvents. The best biosolvents identified are the so far unexplored candidates isosorbide dimethyl ether, acetaldehyde diethyl acetal, rose oxide, and eucalyptol, alongside the known biosolvent 2-methyltetrahydrofuran. This strategy was used for the synthesis of the commercial drugs Fenoprofen and Flurbiprofen.
- Gevorgyan, Ashot,Hopmann, Kathrin H.,Bayer, Annette
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p. 2080 - 2088
(2020/02/20)
-
- Generalized Chemoselective Transfer Hydrogenation/Hydrodeuteration
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A generalized, simple and efficient transfer hydrogenation of unsaturated bonds has been developed using HBPin and various proton reagents as hydrogen sources. The substrates, including alkenes, alkynes, aromatic heterocycles, aldehydes, ketones, imines, azo, nitro, epoxy and nitrile compounds, are all applied to this catalytic system. Various groups, which cannot survive under the Pd/C/H2 combination, are tolerated. The activity of the reactants was studied and the trends are as follows: styrene'diphenylmethanimine'benzaldehyde'azobenzene'nitrobenzene'quinoline'acetophenone'benzonitrile. Substrates bearing two or more different unsaturated bonds were also investigated and transfer hydrogenation occurred with excellent chemoselectivity. Nano-palladium catalyst in situ generated from Pd(OAc)2 and HBPin extremely improved the TH efficiency. Furthermore, chemoselective anti-Markovnikov hydrodeuteration of terminal aromatic olefins was achieved using D2O and HBPin via in situ HD generation and discrimination. (Figure presented.).
- Wang, Yong,Cao, Xinyi,Zhao, Leyao,Pi, Chao,Ji, Jingfei,Cui, Xiuling,Wu, Yangjie
-
supporting information
p. 4119 - 4129
(2020/08/10)
-
- Cyclohexyl-Fused, Spirobiindane-Derived, Phosphine-Catalyzed Synthesis of Tricyclic ?3-Lactams and Kinetic Resolution of ?3-Substituted Allenoates
-
A C2-symmetric chiral phosphine catalyst, NUSIOC-Phos, which can be easily derived from cyclohexyl-fused spirobiindane, was introduced. A highly enantioselective domino process involving pyrrolidine-2,3-diones and γ-substituted allenoates catalyzed by NUSIOC-Phos has been disclosed. Diastereospecific tricyclic γ-lactams containing five contiguous stereogenic centers were obtained in high yields and with nearly perfect enantioselectivities. A kinetic resolution process of racemic γ-substituted allenoates was developed for the generation of optically enriched chiral allenoates.
- Wu, Mingyue,Han, Zhaobin,Li, Kaizhi,Wu, Ji'En,Ding, Kuiling,Lu, Yixin
-
supporting information
p. 16362 - 16373
(2019/10/16)
-
- Regioselectivity inversion tuned by iron(iii) salts in palladium-catalyzed carbonylations
-
Impactful regioselectivity control is crucial for cost-effective chemical synthesis. By using cheap and abundant iron(iii) salts, the hydroxycarbonylations of both aromatic and aliphatic alkenes were significantly enhanced in both reactivity and selectivity (iso/n or n/iso up to >99:1). Moreover, Pd-catalyzed carbonylation selectivity can be switched from branched to linear by using different Fe(iii) salts. In addition, similar results were obtained for the carbonylation of secondary alcohols.
- Huang, Zijun,Cheng, Yazhe,Chen, Xipeng,Wang, Hui-Fang,Du, Chen-Xia,Li, Yuehui
-
supporting information
p. 3967 - 3970
(2018/04/23)
-
- Synthesis and anticancer activity of some 1H-inden-1-one substituted (Heteroaryl)acetamide derivatives
-
Background: The synthesis of 2-[3/4-((6-substituted-1-oxo-2,3-dihydro-1H-inden-2-ylidene)methyl)phenoxy]-N-(heteroaryl)acetamide derivatives and the investigation of their anticancer activity were studied. Methods: 2-(3/4-Hydroxybenzylidene)-6-substituted-2,3-dihydro-1H-inden-1-ones were reacted with suitable 2-chloroacetamides to give 2-[3/4-((6-substituted-1-oxo-2,3-dihydro-1H-inden-2-ylidene) methyl)phenoxy]-N-(heteroaryl)acetamide derivatives. Results: The structure elucidation of the newly synthesised 16 compounds was performed by IR, 1H-NMR, mass spectroscopic data and elemental analyses. The anticancer screening was carried out in National Cancer Institute (NCI), USA. Conclusion: Compound 3e (2-(3-((6-chloro-1-oxo-2,3-dihydro-1H-inden-2-ylidene)methyl)phenoxy)-N-(thiazol-2-yl)acetamide), exhibited highest growth inhibition against the leukaemia (61.47%), non-small cell lung cancer (79.31%) and breast cancer (62.82%) cell lines.
- Karaburun, Ahmet Cagri,Gundogdu-Karaburun, Nalan,Yurttas, Leyla,Kayagil, Ismail,Demirayak, Seref
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p. 111 - 118
(2019/01/04)
-
- CARBAMATE DERIVATIVE COMPOUNDS, PROCESSES FOR PREPARING THEM AND THEIR USES
-
The present invention relates to a pharmaceutical composition for treating or preventing CNS disorders containing a carbamate derivative compound and/or pharmaceutically acceptable salt thereof as an active ingredient. Furthermore, the present invention relates to a method for treatment or prevention CNS disorders comprising administering a carbamate derivative compound in a pharmaceutically effective amount to a subject in need of treatment or prevention of CNS disorders.
- -
-
Paragraph 402-403
(2017/09/15)
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- A Ligand-Directed Catalytic Regioselective Hydrocarboxylation of Aryl Olefins with Pd and Formic Acid
-
An effective Pd-catalyzed hydrocarboxylation of aryl olefins with Ac2O and formic acid is described. A variety of 2- and 3-arylpropanoic acids can be regioselectively formed by the judicious choice of ligand without the use of toxic CO gas.
- Liu, Wei,Ren, Wenlong,Li, Jingfu,Shi, Yuan,Chang, Wenju,Shi, Yian
-
supporting information
p. 1748 - 1751
(2017/04/11)
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- Metal-Free Chemoselective Oxidative Dehomologation or Direct Oxidation of Alcohols: Implication for Biomass Conversion
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A transition metal-free, chemoselective reaction was performed using the sodium tert-butoxide-oxygen (NaOtBu-O2) system, resulting in either oxidative dehomologation or direct oxidation of alcohols. In particular, the newly developed protocol may be used to predict the major product formed, which depends on alkyl chain length of the alcohols and reaction conditions. The rational mechanism of this transformation was also demonstrated by performing an 18O isotopic labelling experiment. This protocol presents a straightforward method for biomass conversion of a lignin model compound to phenol and benzoic acid.
- Kim, Sun Min,Shin, Hun Yi,Kim, Dong Wan,Yang, Jung Woon
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p. 241 - 245
(2016/02/27)
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- The method used for the selective demetalization benzylmethacrylic selective hydrogenation catalyst
-
PROBLEM TO BE SOLVED: To provide a debenzylation technology of efficiently hydrogenating a benzyl group as a protective group without decomposing or hydrogenating a halogen atom and an acyl group in an aromatic halide compound or an aromatic ketone compound.SOLUTION: In a debenzylation method, a hydrogen gas is reacted, in an ester medium, with a carboxylic acid benzyl ester represented by formula (I) in the presence of a β zeolite carrying a palladium ingredient, and a carboxylic acid compound represented by formula (II) is obtained. In the formula: Ar is an aromatic ring group or a heterocyclic group having one or substituents which can be hydrogenated; Zis a single bond, -CHCH- or -CH=CH-; Zis a single bond or -CHCH-; and Bn is a benzyl group.
- -
-
Paragraph 0033; 0034; 0035; 0036; 0037; 0038
(2016/12/22)
-
- Synthesis and anticancer activity of some 2-[3/4-(2-substituted phenyl-2-oxoethoxy)benzylidene]-6-substituted-2,3-dihydro-1H-inden-1-one derivatives
-
The synthesis of 2-[3/4-(2-substituted phenyl-2-oxoethoxy)benzylidene]-6- substituted-2,3-dihydro-1H-inden-1-one derivatives and the investigation of their anticancer activity were studied. 2-(3- or 4-Hydroxybenzylidene)-6- substituted-2,3-dihydro-1H-inden-1-ones were reacted with suitable 2-bromoacetophenones to give 2-[3/4-(2-substituted phenyl-2-oxoethoxy) benzylidene]-6-substituted-2,3-dihydro-1H-inden-1-one derivatives. The structure elucidation of the synthesised compounds was performed by IR, 1H-NMR, mass spectroscopic data and elemental analyses. The anticancer screening was carried out in National Cancer Institute (NCI), USA. Notable activity was obtained for some compounds.
- Gundogdu-Karaburun, Nalan,Karaburun, Ahmet Cagri,Demirayak, Seref,Kayagil, Ismail,Yurttas, Leyla
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p. 578 - 585
(2014/05/20)
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- Palladium on carbon-bromobenzene mediated esterification and transesterification
-
A series of carboxylic acids were converted into their corresponding esters using the Pd/C catalyzed hydrogenation conditions in the presence of catalytic bromobenzene in alcohols and the method could also be applicable for the transesterification of esters. Good to excellent yields were obtained for different aliphatic or aromatic starting materials. The success of this esterification relies on the in situ generation of hydrobromic acid (HBr) from bromobenzene which provides a mild and acidic reaction environment. The palladium catalyst exhibits a remarkable activity and is reusable for up-to three consecutive cycles.
- Aavula, Sanjeev Kumar,Chikkulapalli, Anil,Hanumanthappa,Jyothi, Indira,Vinod Kumar,Manjunatha, Sulur G.
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p. 5690 - 5694
(2013/09/24)
-
- Improved synthesis of natural ester sintenin and its analogues via Wittig reaction
-
The synthesis of a cytotoxic natural ester sintenin (7a) and twenty eight of its analogues including nitrogen-containing heterocyclic indole moiety (7b-7t), saturated (10a-10d) and unsaturated (10e-10h) amides were carried out by convenient route via one-pot Wittig reaction in aqueous medium with improved yield. A systematic structure activity relationship of sintenin ester was designed by chemically modified derivatives in order to get better cytotoxicity.
- Sharma, Mukul,Rajesh, U. Chinna,Rawat, Diwan S.
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p. 1853 - 1860
(2014/01/17)
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- Anchored Pd-complexes in mesoporous supports: Synthesis, characterization and catalysis studies for carbonylation reactions
-
Pd(pyca)(PPh3)(OTs) [pyca = 2-picolinate] complex is efficiently anchored inside different mesoporous matrices, such as MCM-41, MCM-48, SBA-15 using a molecular aminopropyl tether moiety employing different synthesis strategies. Thorough characterization of the materials using powder XRD, multinuclear (13C, 29Si, 31P) CP-MAS NMR, XPS, SEM, N2-sorption studies etc. confirmed the successful anchoring of the palladium complex to the walls of the support matrices thus establishing the synthesis protocols unambiguously. The catalysts were found to be highly active and selective for the carbonylation of different aryl olefins and alcohols. Consecutive recycling and successful reuse proved the stability and true heterogeneous nature of all the anchored catalysts, which is a substantial advancement over the existing heterogeneous catalysts for carbonylation.
- Sarkar, Bibhas R.,Chaudhari, Raghunath V.
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p. 154 - 173
(2013/01/15)
-
- A simple and straightforward approach toward selective C=C bond reduction by hydrazine
-
A simple and straightforward method for reducing the C=C double bond with hydrazine is described. A number of representative C=C bonds in various steric and electronic environments were examined. Substituted alkenes can be selectively reduced in EtOH in the presence of hydrazine to give the corresponding products in up to 100% yields.
- Chen, Hao,Wang, Jianmin,Hong, Xuechuan,Zhou, Hai-Bing,Dong, Chune
-
supporting information
p. 758 - 761
(2012/11/07)
-
- Raney nickel-catalyzed hydrogenation of unsaturated carboxylic acids with sodium borohydride in water
-
A mild, selective, and green method for the reduction of unsaturated carboxylic acids with sodium borohydride-Raney nickel (W6) system in water is reported. This method is practical and safe and avoids use of organic solvents. Taylor & Francis Group, LLC.
- Rao, Gopal Krishna,Gowda, Narendra B.,Ramakrishna, Ramesha A.
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experimental part
p. 893 - 904
(2012/02/01)
-
- Identification and optimization of tetrahydro-2H-3-benzazepin-2-ones as squalene synthase inhibitors
-
Novel squalene synthase inhibitors are disclosed. SAR and pharmacological profile of selected compounds are discussed.
- Griebenow, Nils,Flessner, Timo,Buchmueller, Anja,Raabe, Martin,Bischoff, Hilmar,Kolkhof, Peter
-
scheme or table
p. 2554 - 2558
(2011/05/15)
-
- Synthesis and biological evaluation of 9-oxo-9hindeno[1,2-b]pyrazine-2,3- dicarbonitrile analogues as potential inhibitors of deubiquitinating enzymes
-
High-throughput screening highlighted 9-oxo-9H-indeno[1,2-b]pyrazine-2,3- dicarbonitrile (1) as an active inhibitor of ubiquitin-specific proteases (USPs), a family of hydrolytic enzymes involved in the removal of ubiquitin from protein substrates. The chemical behavior of compound 1 was examined. Moreover, the synthesis and in vitro evaluation of new compounds, analogues of 1, led to the identification of potent and selective inhibitors of the deubiquitinating enzyme USP8.
- Colombo, Matteo,Vallese, Stefania,Peretto, Ilaria,Jacq, Xavier,Rain, Jean-Christophe,Colland, Frederic,Guedat, Philippe
-
experimental part
p. 552 - 558
(2010/12/25)
-
- 1,4-Cyclohexadiene with Pd/C as a rapid, safe transfer hydrogenation system with microwave heating
-
A method for the rapid, safe hydrogenation of alkenes and deprotection of benzyl ethers and carboxybenzyl amides is described using catalytic transfer hydrogenation under microwave heating conditions. Commonly available Pd/C catalyst is extremely effective with 1,4-cyclohexadiene as the hydrogen transfer source. In general, the reactions are complete within five minutes at 100 °C.
- Quinn, John F.,Razzano, Dana A.,Golden, Kathryn C.,Gregg, Brian T.
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scheme or table
p. 6137 - 6140
(2009/04/05)
-
- THERAPEUTIC FLUOROETHYLCYANO GUANIDINES
-
Disclosed herein is compound having a formula as described herein. Therapeutic methods, compositions, and medicaments related thereto are also disclosed.
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-
Page/Page column 15
(2008/12/04)
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- Aromatic chlorination of ω-phenylalkylamines and ω- phenylalkylamides in carbon tetrachloride and α,α,α- trifluorotoluene
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The aromatic halogenation of simple alkylbenzenes with chlorine proceeds smoothly in acetic acid but is much less efficient in less polar solvents. By contrast chlorination of ω-phenylalkylamines, such as 3-phenylpropylamine, occurs readily in either acetic acid, carbon tetrachloride or α,α,α-trifluorotoluene, and in the latter solvents gives high proportions of ortho-chlorinated products. These effects are attributable to the involvement of N-chloroamines as reaction intermediates, with intramolecular delivery of the chlorine electrophile. ω-Phenylalkylamides, such as 3-phenylpropionamide, also easily undergo aromatic chlorination in carbon tetrachloride and α,α,α-trifluorotoluene. These reactions generally show a first-order dependence on the substrate concentration, but not on the amount of chlorine. With carbon tetrachloride, very similar reaction rates are observed with chlorine concentrations ranging from 0.1-1.5 M. In α,α,α-trifluorotoluene, the rates reach a plateau at a chlorine concentration of approximately 0.2 M. These features indicate that the reactions proceed via the formation of intermediates which evidence suggests may be the corresponding O-chloroimidates. Irrespective of the mechanistic details, the reactions are remarkably rapid, being faster than analogous reactions in acetic acid and three to four orders of magnitude more rapid than reactions of simple alkylbenzenes in carbon tetrachloride. Therefore, chlorination of the amines and amides may be accomplished without the need for highly polar solvents, added catalysts or large excesses of chlorine, which are often employed for electrophilic aromatic substitutions. Although the use of carbon tetrachloride is becoming increasingly impractical due to environmental concerns, the trifluorotoluene is a suitable alternative. The Royal Society of Chemistry 2006.
- O'Connell, Jenny L.,Simpson, Jamie S.,Dumanski, Paul G.,Simpson, Gregory W.,Easton, Christopher J.
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p. 2716 - 2723
(2008/02/08)
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- The discovery and synthesis of novel adenosine receptor (A2A) antagonists
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In high throughput screening of our file compounds, a novel structure 1 was identified as a potent A2A receptor antagonist with no selectivity over the A1 adenosine receptor. The structure-activity relationship investigation using 1 as a template lead to identification of a novel class of compounds as potent and selective antagonists of A2A adenosine receptor. Compound 26 was identified to be the most potent A2A receptor antagonist (Ki = 0.8 nM) with 100-fold selectivity over the A1 adenosine receptor.
- Matasi, Julius J.,Caldwell, John P.,Hao, Jinsong,Neustadt, Bernard,Arik, Leyla,Foster, Carolyn J.,Lachowicz, Jean,Tulshian, Deen B.
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p. 1333 - 1336
(2007/10/03)
-
- Design and synthesis of a new polymer-supported Evans-type oxazolidinone: An efficient chiral auxiliary in the solid-ph ase asymmetric alkylation reactions
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Wang resin-supported Evans' chiral auxiliary (23) was designed based on a novel polymer-anchoring strategy, which utilizes the 5-position of the oxazolidinone ring, and its new synthetic route applicable to multi-gram preparation in just a day was developed. Solid-phase Evans' asymmetric alkylation on 23-derived N-acylimide resin and following lithium hydroperoxide-mediated chemoselective hydrolysis afforded the corresponding α-branched carboxylic acids in desired high stereoselectivities (up to 97% ee) and moderate to good overall yield (up to 70%, for 3 steps), which were comparable to those of the conventional solution-phase methods. Furthermore, recovery and recycling of the polymer-supported chiral auxiliary were successfully achieved without decreasing the stereoselectivity of the product. Therefore, this is the first successful example that the solid-phase Evans' asymmetric enolate-alkylation was efficiently performed on the solid-support, and it is concluded that the connection to the solid-support via the 5-position of the oxazolidinone ring is an ideal strategy in the solid-phase Evans' chiral auxiliary.
- Kotake, Tomoya,Hayashi, Yoshio,Rajesh,Mukai, Yoshie,Takiguchi, Yuka,Kimura, Tooru,Kiso, Yoshiaki
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p. 3819 - 3833
(2007/10/03)
-
- TETRAHYDROBENZO[D]AZEPIN-2- ONE DERIVATIVES AND THE USE THEREOF FOR TREATING CARDIOVASCULAR DISEASES
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The invention concerns novel tetrahydrobenzo[d]azepin-2-one derivatives, a method for the production thereof, their use for treating and/or preventing diseases, and their use for producing medicaments for treating and/or preventing diseases, preferably for treating and/or preventing cardiovascular diseases, particularly dyslipidemias, arteriosclerosis, restenosis and ischemias.
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Page/Page column 19; 36
(2008/06/13)
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- Synthesis of 1,4:3,6-dianhydro-d-mannitol 2,5-(hydrogenphosphate) and its usage in palladium-catalyzed hydroxycarbonylation of styrene
-
Phosphorylation of 1,4:3,6-dianhydro-d-mannitol by phosphorus oxychloride in the presence of triethylamine followed by hydrolysis gave a cyclie hydrogen phosphate, which has the crystal structure of 6-hydroxy-6-oxo-2,5,7,10-tetraoxa-6-phospha-tricyclo[6.3.0.04,11]undecane. It was used as a chiral ligand in palladium-catalyzed hydroxycarbonylation of styrene. The regioselectivity was good, but the optical yield was limited.
- Jiang, Biao,Huang, Zuo-Gang,Cheng, Ke-Jun
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p. 2797 - 2803
(2007/10/03)
-
- Samarium diiodide reduction of cinnamic acids
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The method for measuring SmI2 reduction rates is expanded to a wider range of organic compounds by using not only GC or GC/MS, but also HPLC as the detecting tool. The reduced substrates are not only confined to water insoluble compounds or low boiling compounds only. Water soluble cinnamic acid derivatives of high boiling points are chosen for this application. The absolute rate constants of SmI2 reduction of cinnamic acid in the presence of hexamethyl phosphoramide or t-butanol is considered as a suitable proton source in this reaction. The rates are dependent on substrates and additives as: Rate · [t-BuOH][Cinnamic acid] and Rate · [HMPA][Cinnamic acid] The reduction rates of α-methylcinnamic acid, 2-methylcinnamic acid, 4-methylcinnamic acid, 2-methoxycinnamic acid, 3-methoxycinnamic acid, 4-methoxycinnamic acid, 2-hydroxycinnamic acid, 3-hydroxycinnamic acid, 4-hydroxycinnamic acid, 2-chlorocinnamic acid, 3-chlorocinnamic acid, 4-chlorocinnamic acid were carefully measured to study the substituent effect.
- Lin, Tzuen-Yeuan,Fuh, Ming-Ren,Tsau, Chi-Yu
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p. 917 - 921
(2007/10/03)
-
- Fluorescence resonance energy transfer (FRET) as a high-throughput assay for coupling reactions. Arylation of amines as a case study
-
A solution-phase assay based on fluorescence resonance energy transfer (FRET) was developed for high-throughput screening of palladium catalyzed aminations of aryl halides. Dansylpiperazine was used as the fluorescent component and a chloro- or bromoarene tagged with an azodye as the quenching partner. Fluorescence intensities of reaction aliquots correlated linearly with reaction yield after dilution to appropriate concentrations. A library of 119 phosphine and heterocyclic carbene ligands was evaluated in duplicate reactions of two combinations. In general, the FRET assay displayed excellent reproducibility, with less than 5% of the duplicate experiments showing significant variability in yields. Among reactions producing greater than 50% yield, the average percent uncertainty was just 5%. For a small subset of sterically hindered ligands, differences in yields between 10 and 20% were observed between the substrates bearing dyes for the FRET assay and substrates that are unfunctionalized. However, the remaining catalyst combinations gave yields similar to those expected from literature precedent. In addition to an evaluation of the accuracy of the FRET assay, this work includes the use of the FRET assay to investigate relative activities of various catalysts for the amination of aryl bromides and chlorides and to find conditions for aminations in more polar solvents. Reactions with K3PO4 base in aqueous mixtures of polar and nonpolar organic solvents were shown to be appropriate for the amination chemistry.
- Stauffer, Shaun R.,Hartwig, John F.
-
p. 6977 - 6985
(2007/10/03)
-
- Tripeptide α-ketoamides
-
A novel class of tripeptide α-ketoamides useful for selectively inhibiting serine proteases, selectively inhibiting cysteine proteases, generally inhibiting all serine proteases, and generally inhibiting all cysteine proteases, having the formula M1—AA—AA—AA—CO—NR3R4.
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-
- The effect of vinyl esters on the enantioselectivity of the lipase-catalysed transesterification of alcohols
-
The enantioselectivity of the lipase from Pseudomonas cepacia (PCL) in the transesterification of 2-phenyl-1-propanol 1 was studied using a series of vinyl 3-arylpropanoates as acyl donors. The most enantioselective transesterification reaction of the alcohol was attained by using vinyl 3-(p-iodophenyl)- or 3-(p-trifluoromethylphenyl)propanoates, with enantiomer ratios, E, of 116 and 138, respectively. Vinyl 3-phenylpropanoate was also effective for the resolution of 1 mediated by lipases from P. fluorescens and porcine pancreas and for the PCL-catalysed transesterification of several 2-phenyl-1-alkanols. The enantiomeric resolution of 1 was practically carried out by the first enantioselective transesterification using PCL and vinyl 3-(p-iodophenyl)propanoate to afford (R)-1 and then the enantioselective hydrolysis of the resultant ester to afford (S)-1.
- Kawasaki, Masashi,Goto, Michimasa,Kawabata, Shigeki,Kometani, Tadashi
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p. 585 - 596
(2007/10/03)
-
- Regioselective intramolecular oxidation of phenols and anisoles by dioxiranes generated in situ
-
A novel method for regioselective oxidation of phenols and anisoles has been developed in which dioxiranes, generated in situ from ketones and Ozone, oxidize phenol derivatives in an intramolecular fashion. A series of ketones with electron-withdrawing groups, such as CF3, COOMe, and CH2Cl, were attached to phenols, anisoles, or aryl rings via a C2 or C3 methylene linker. In a homogeneous solvent system of CH3CN and H2O, oxidation of phenol derivatives 1-10 afforded spiro 2-hydroxydienones in 24-55% yields regardless of the presence of other substituents (ortho Me, meta Me or Br) on the aryl ring and the length of the linker. Experimental evidences were provided to support the mechanism that involves a regioselective π bond epoxidation of aryl rings followed by epoxide rearrangement and hemiketal formation.
- Yang, Dan,Wong, Man-Kin,Yan, Zheng
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p. 4179 - 4184
(2007/10/03)
-
- TETRAPEPTIDE ALPHA-KETOAMIDES
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A novel class of tetrapeptide α-ketoamides useful for selectively inhibiting serine proteases, selectively inhibiting cysteine proteases, generally inhibiting all serine proteases, and generally inhibiting all cysteine proteases, having the formula M 1--A
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-
-
- Simple, safe, large scale synthesis of 5-arylmethyl-2,2-dimethyl-1,3-dioxane-4,6-diones and 3-aryl-propanoic acids
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Reaction of aryl aldehydes with Meldrum's acid 2 in the presence of formic acid and triethylamine with 5-arylmethyl Meldrum's acid derivatives 4 at room temperature, whereas at 80-100°C 3-arylpropanoic acids 5 are formed.
- Toth,Kover
-
p. 3067 - 3074
(2007/10/03)
-
- A Formal Total Synthesis of the ACE Inhibitor K-13. An Application of Arene-Ruthenium Chemistry to Complex Chemical Synthesis
-
Stoichiometric ruthenium activation of 4-chlorophenylalanine derivatives toward nucleophilic substitution, using phenoxide nucleophiles that are derived from protected dipeptides, allowed the formation of isodityrosine derivatives that are synthetic precursors to the ACE inhibitor K-13.An evaluation of carboxyl blocking groups revealed that a 2-bromoethyl ester is the most useful in terms of its compatibility with ruthenium complexation and subsequent nucleophile addition but that its removal is problematic.Conversion to iodoethyl ester using Finkelstein reaction conditions, in the presence of the peptide and amino acid functionality, provided a solution to this problem, since the iodoethyl group was easily removed on treatment with samarium diiodide.
- Pearson, Anthony J.,Lee, Kieseung
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p. 2304 - 2313
(2007/10/02)
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- Rate of decarboxylation, monitored via the key enzyme-bound enamine, of conjugated α-keto acids by pyruvamide activated pyruvate decarboxylase is kinetically competent with turnover
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The rate of formation of the covalent thiamin diphosphate-bound enamine/C2-α-carbanion intermediate monitored at 440 nm from conjugated mechanism-based inhibitors of the structure (E)-YC6H4CH=CHCOCOOH, where Y = p-Cl, m-NO2, m-CF3, was determined in the absence and presence of the allosteric activator pyruvamide on brewers' yeast pyruvate decarboxylase (PDC, E.C. 4.1.1.1). For all three compounds the first-order rate constant for enamine formation was accelerated from 15-150-fold by conversion of the enzyme to its activated form. The rate constant for enamine formation is 102-103 times faster than those estimated for inactivation. Comparing the kcat (0.44 s-1) to the rate constant for decarboxylation (0.653 s-1) for Y = p-Cl leads one to conclude that enamine formation is kinetically competent to participate in the turnover pathway. Based on the maximum absorbance developed at 440 nm, and the ε= 104 at this wavelength for a model compound (Y = H), there appear to be four active sites per tetrameric holoenzyme. The kcat/active site for pyruvate is estimated at ca. 40 s-1 at 20°C, and the decarboxylation rate constant for pyruvate can be estimated to be 80 s-1 /active site at 20°C, assuming decarboxylation and product release are equal in kinetic significance. The rate constants for decarboxylation by activated PDC for Y = m-NO2, m-CF3 (53 and 69 s-1) are comparable to this estimated decarboxylation rate constant for pyruvate (80 s-1). The k's for Y = m-NO2, m-CF3 are also similar in magnitude to the decarboxylation rate constant (62-80 s-1 at 22°C) reported for pyruvate oxidase, an enzyme with considerable sequence homology to PDC, and one that follows the same mechanism through decarboxylation.
- Menon-Rudolph, Sunitha,Nishikawa, Sadakatsu,Zeng, Xiaoping,Jordan, Frank
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p. 10110 - 10112
(2007/10/02)
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- Arylalkylaminobenzoic acids
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This disclosure describes novel [Bis(phenyl or substituted phenyl)alkyl]amino benzoic acids, esters, and derivatives thereof. These compounds are useful pharmaceutical agents for ameliorating atherosclerosis by inhibiting the formation and development of atherosclerotic lesions in the arterial walls of mammals.
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- REDUCTION OF CARBON-CARBON DOUBLE BONDS AND HYDROGENOLYSIS BY SODIUM HYPOPHOSPHITE
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Sodium hypophosphite plus palladium-charcoal is a mild, economical, selective system for the reduction of carbon-carbon double bonds and hydrogenolysis of benzyl ethers and benzyl carbonates.
- Sala, Roberto,Doria, Gianfederico,Passarotti, Carlo
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p. 4565 - 4568
(2007/10/02)
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