- Synthesis of highly substituted pyrrolidines through 1,3-dipolar cycloaddition reaction of N-metalated azomethine ylides with triarylideneacetylacetone as dipolarophile using titanocene dichloride
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The 1,3-dipolar cycloaddition reaction of tryarylideneacetyacetone derivatives with N-metalated azomethine ylides in the presence of titanocene dichloride and triethylamine has been investigated. This two-step synthetic sequence is very efficient and yielded the highly substituted pyrrolidines in good yields. The structure and stereochemistry of one of the products has been established by single-crystal x-ray structure and spectroscopic techniques.
- Murugan, Ramalingam,Raghunathan,Narayanan, S. Sriman
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Read Online
- Nucleophilic reactivities of Schiff base derivatives of amino acids
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Treatment of α-imino esters derived from glycine esters and benzophenone or benzaldehydes with potassium tert butoxide in DMSO gave persistent solutions of carbanions at 20 °C. The kinetics of their reactions with quinone methides and benzylidene malonates (reference electrophiles) have been followed photometrically under pseudo-first order conditions. The reactions followed second-order rate laws. Since addition of 18-crown-6 ether did not affect the reaction rates, the measured rate constants correspond to the reactions of the non-paired carbanions. Plots of the second-order rate constants against the electrophilicity parameters E of the electrophiles are linear, which allowed us to derive the nucleophile-specific parameters N and sN, according to the linear Gibbs energy relationship lg k2(20 °C) = sN(N + E). The Ph2C = N- and PhCH = N- groups act as very weak electron acceptors with the consequence that Ph2C = N-CH–-CO2R and PhCH = N-CH–-CO2R have a similar nucleophilicity as Ph-CH–-CO2Et, the anion of ethyl phenylacetate.
- Timofeeva, Daria S.,Ofial, Armin R.,Mayr, Herbert
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supporting information
p. 459 - 463
(2019/01/04)
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- Well-Designed Phosphine-Urea Ligand for Highly Diastereo- and Enantioselective 1,3-Dipolar Cycloaddition of Methacrylonitrile: A Combined Experimental and Theoretical Study
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A novel chiral phosphine-urea bifunctional ligand has been developed for Cu-catalyzed asymmetric 1,3-dipolar cycloaddition of iminoesters with methacrylonitrile, a long-standing challenging substrate in asymmetric catalysis. Distortion-interaction energy analysis based on density functional theory (DFT) calculations reveals that the distortion energy plays an important role in the observed enantioselectivity, which can be attributed to the steric effect between the phosphine ligand and the dipole reactant. DFT calculations also indicate that nucleophilic addition is the enantioselectivity-determining step and hydrogen bonding between the urea moiety and methacrylonitrile assists in control of the diastereo- and enantioselectivity. By a combination of metal catalysis and organocatalysis, excellent diastereo- and enantioselectivities (up to 99:1 diastereomeric ratio, 99% enantiomeric excess) as well as good yields are achieved. A wide range of substitution patterns of both iminoester and acrylonitrile is tolerated by this catalyst system, providing access to a series of highly substituted chiral cyanopyrrolidines with up to two quaternary stereogenic centers. The synthetic utility is demonstrated by enantioselective synthesis of antitumor agent ETP69 with a pivotal nitrile pharmacophore and an all-carbon quaternary stereogenic center.
- Xiong, Yang,Du, Zhuanzhuan,Chen, Haohua,Yang, Zhao,Tan, Qiuyuan,Zhang, Changhui,Zhu, Lei,Lan, Yu,Zhang, Min
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supporting information
p. 961 - 971
(2019/01/14)
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- Application of the Cu(i)/TEMPO/O2 catalytic system for aerobic oxidative dehydrogenative aromatization of pyrrolidines
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A Cu(i)/TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy)-catalyzed aerobic oxidative dehydrogenative aromatization reaction of fully saturated pyrrolidines to synthesize multi-substituted pyrroles was developed for the first time. The use of a non-precious metal catalyst, green oxidant and environmentally friendly solvent made the reaction more sustainable.
- Luo, Zheng,Liu, Yan,Wang, Chao,Fang, Danjun,Zhou, Junyu,Hu, Huayou
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supporting information
p. 4609 - 4613
(2019/09/09)
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- An efficient and facile access to highly functionalized pyrrole derivatives
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A straightforward and one-pot synthesis of pyrrolo[3,4-c]pyrrole-1,3-diones via Ag(I)-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with N-alkyl maleimide, followed by readily complete oxidation with DDQ, has been successfully developed. Further transformation with alkylamine/sodium alkoxide alcohol solution conveniently afforded novel polysubstituted pyrroles in good to excellent yields. This methodology for highly functionalized pyrroles performed well over a broad scope of substrates. It is conceivable that this efficient construction method for privileged pyrrole scaffolds could deliver more active compounds for medicinal chemistry research.
- Gao, Meng,Zhao, Wenting,Zhao, Hongyi,Lin, Ziyun,Zhang, Dongfeng,Huang, Haihong
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supporting information
p. 884 - 890
(2018/04/27)
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- Tandem nucleophilic addition-cycloaddition of arynes with α-iminoesters: Two concurrent pathways to imidazolidines
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The tandem nucleophilic addition-cycloaddition reaction has been developed for the synthesis of functionalized imidazolidine derivatives. A variety of α-iminoesters and aryne precursors were well tolerated under the mild reaction conditions. This asymmetric cycloaddition afforded imidazolidine derivatives with high yields, complete regioselectivities, and excellent diastereo- and enantioselectivities. Aryne-induced ylides working as 1,3-dipoles for asymmetric cycloaddition are the notable feature of the present reaction. In the tandem reaction, the [3+2] cycloaddition of aryne-induced ylides with metallized α-iminoesters and metal-catalyzed [3+2] cycloaddition of azomethine ylide with α-iminoesters are two concurrent pathways to imidazolidines.
- Jia, Hao,Guo, Zhenyan,Liu, Honglei,Mao, Biming,Shi, Xueyan,Guo, Hongchao
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supporting information
p. 7050 - 7053
(2018/07/05)
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- Tandem [3 + 2] cycloaddition/1,4-addition reaction of azomethine ylides and aza-o-quinone methides for asymmetric synthesis of imidazolines
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An enantioselective synthesis of biologically important imidazolidines has been achieved via a tandem [3 + 2] cycloaddition/1,4-addition reaction of azomethine ylide and aza-o-quinone methides. With the use of this tool, various imidazolidine derivatives are obtained in good yields with excellent diastereoselectivities and enantioselectivities.
- Jia, Hao,Liu, Honglei,Guo, Zhenyan,Huang, Jiaxing,Guo, Hongchao
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supporting information
p. 5236 - 5239
(2017/11/06)
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- COMPOUNDS AS HEPATITIS C INHIBITORS AND USES THEREOF IN MEDICINE
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Provided herein are compounds as hepatitis C inhibitors and uses thereof in medicine. Specifically, provided herein is a compound of Formula (I) or a stereoisomer, a tautomer, an enantiomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or hepatitis C diseases. Also provided herein are a pharmaceutically acceptable composition containing such compound and a method of treating HCV infection or hepatitis C diseases comprising administering the compound or pharmaceutical composition thereof disclosed herein.
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Paragraph 00172
(2016/09/22)
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- Synthesis method of (1R, 2S)-1-amino-2-vinyl ethyl cyclopropane dicarboxylate
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The invention belongs to the technical field of preparation of anti hepatitis C virus drug intermediates and particularly relates to a synthesis method of (1R, 2S)-1-amino-2-vinyl ethyl cyclopropane dicarboxylate. The synthesis method comprises the specific steps that step one, benzaldehyde, glycine ethyl ester hydrochloride, toluene and triethylamine are used as raw materials to be synthesized into a compound 4; step two, the compound 4 and trans-1,4-dibromo butene react in the toluene and sodium ethoxide to prepare a compound 3; step three, the compound 3 and (2S)-2-[(3,5-dichlorobenzoyl peroxide) oxy] propionic acid react in the toluene, and then isopropyl alcohol and hexane are added to obtain a compound 2; step four, the compound 2 reacts with sodium hydroxide in the toluene to obtain a compound (1R, 2S)-1-amino-2-vinyl ethyl cyclopropane dicarboxylate. The synthesis method is simple in operation and suitable for industrialized production, the raw materials are cheap and easy to obtain, and the obtained target product is high in purity and chiral purity.
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Paragraph 0015; 0016; 0017
(2016/10/09)
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- Diastereoselective Trifluoroacetylation of Highly Substituted Pyrrolidines by a Dakin-West Process
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A robust approach allowing for the efficient trifluoroacetylation of a series of highly substituted pyrrolidines in a diastereoselective manner is reported. The transformation is based on a Dakin-West reaction of advanced pyrrolidine 2-carboxylic acid derivatives that can be assembled stereoselectively in four synthetic steps. Importantly, this work demonstrates how the introduction of lateral substituents on the pyrrolidine scaffold enables the generation of the desired trifluoroacetylation products, which was not possible previously due to the exclusive formation of trifluoromethylated oxazoles (vide infra). In the course of this work we succeeded for the first time in isolating and characterizing (HRMS, IR, 1H, 13C and 19F NMR, X-ray) different intermediates of the Dakin-West reaction allowing us to probe its mechanism.
- Baumann, Marcus,Baxendale, Ian R.
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p. 11898 - 11908
(2016/12/09)
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- Three-component domino process for the pyrrolizine skeleton via [3 + 2]-cycloaddition-enamine cyclization triggered by a gold catalyst
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Pyrrolizines are bicyclic fused azaheterocycles with a bridgehead nitrogen contained in a core skeleton and are often found in biologically active compounds. Despite their importance, there have been few reports on concise and flexible syntheses of pyrrolizines. A novel one-pot, convergent method is described for pyrrolizines by simple mixing of iminoesters, acetylenes, and dipolarophiles in the presence of a cationic gold catalyst and an acid additive. This domino process affords multisubstituted pyrrolizines without handling unstable intermediates.
- Sugimoto, Kenji,Yamamoto, Nozomi,Tominaga, Daisuke,Matsuya, Yuji
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supporting information
p. 1320 - 1323
(2015/03/14)
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- Cu(I)-Catalyzed Highly Enantioselective [3 + 3] Cycloaddition between Two Different 1,3-Dipoles, Phthalazinium Dicyanomethanides and Iminoester-Derived Azomethine Ylides
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(Chemical Equation Presented). The Cu(I)-catalyzed highly enantioselective [3 + 3] cycloaddition between two different 1,3-dipoles, phthalazinium dicyanomethanides and iminoester-derived azomethine ylides, has been achieved under mild reaction conditions, providing novel chiral heterocyclic compounds, 2,3,4,11b-tetrahydro-1H-pyrazino[2,1-a]phthalazine derivatives, in high yields with excellent diastereo- and enantioselectivies (up to 99% yield, 99% ee, >20:1 dr).
- Yuan, Chunhao,Liu, Honglei,Gao, Zhenzhen,Zhou, Leijie,Feng, Yalin,Xiao, Yumei,Guo, Hongchao
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supporting information
p. 26 - 29
(2015/07/28)
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- Tricyclic analogues of epidithiodioxopiperazine alkaloids with promising in vitro and in vivo antitumor activity
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Epipolythiodioxopiperazine (ETP) alkaloids are structurally elaborate alkaloids that show potent antitumor activity. However, their high toxicity and demonstrated interactions with various biological receptors compromises their therapeutic potential. In an effort to mitigate these disadvantages, a short stereocontrolled construction of tricyclic analogues of epidithiodioxopiperazine alkaloids was developed. Evaluation of a small library of such structures against two invasive cancer cell lines defined initial structure-activity relationships (SAR), which identified 1,4-dioxohexahydro-6H-3,8a-epidithiopyrrolo[1,2-a]pyrazine 3c and related structures as particularly promising antitumor agents. ETP alkaloid analogue 3c exhibits low nanomolar activity against both solid and blood tumors in vitro. In addition, 3c significantly suppresses tumor growth in mouse xenograft models of melanoma and lung cancer, without obvious signs of toxicity, following either intraperitoneal (IP) or oral administration. The short synthesis of molecules in this series will enable future mechanistic and translational studies of these structurally novel and highly promising clinical antitumor candidates.
- Baumann, Marcus,Dieskau, André P.,Loertscher, Brad M.,Walton, Mary C.,Nam, Sangkil,Xie, Jun,Horne, David,Overman, Larry E.
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p. 4451 - 4457
(2015/07/27)
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- Metal-catalyzed [6 + 3] cycloaddition of tropone with azomethine ylides: A practical access to piperidine-fused bicyclic heterocycles
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The first metal-catalyzed [6 + 3] cycloaddition of tropone with azomethine ylides has been developed. With the use of a chiral ferrocenylphosphine- copper(I) complex as the catalyst, the asymmetric variant of the [6 + 3] cycloaddition has also been successfully achieved. The reactions proceeded smoothly under mild conditions, affording piperidine-fused bicyclic heterocycles in moderate to high yields with good to excellent diastereo-and enantioselectivies. The procedures are operationally simple and the catalysts are cheap and readily accessible, thus providing a practical approach to piperidine-fused bicyclic heterocycles.
- Liu, Honglei,Wu, Yang,Zhao, Yan,Li, Zhen,Zhang, Lei,Yang, Wenjun,Jiang, Hui,Jing, Chengfeng,Yu, Hao,Wang, Bo,Xiao, Yumei,Guo, Hongchao
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supporting information
p. 2625 - 2629
(2014/03/21)
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- A rapid and divergent access to chiral azacyclic nucleoside analogues via highly enantioselective 1,3-dipolar cycloaddition of β-nucleobase substituted acrylates
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A rapid and divergent access to chiral azacyclic nucleoside analogues has been established via highly exo-selective and enantioselective 1,3-dipolar cycloaddition of azomethine ylides with β-nucleobase substituted acrylates. Using 1 mol% of a chiral copper complex, various chiral azacyclic nucleoside analogues were obtained in high yields, excellent exo-selectivities and enantioselectivities (98 to >99% ee). This journal is
- Yang, Qi-Liang,Xie, Ming-Sheng,Xia, Chao,Sun, Huan-Li,Zhang, Dan-Jie,Huang, Ke-Xin,Guo, Zhen,Qu, Gui-Rong,Guo, Hai-Ming
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supporting information
p. 14809 - 14812
(2014/12/11)
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- Stereospecific synthesis of pyrrolidines with varied configurations via 1,3-dipolar cycloadditions to sugar-derived enones
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Enantiomerically pure pyrrolidines have been obtained by 1,3-dipolar cycloaddition of stabilized azomethine ylides and sugar enones (dihydropyranones) derived from pentoses. Thus, the S-enone (menthyl 3,4-dideoxy-(1S)-pent-3-enopyranosid-2-ulose) was prepared from d-xylose, while the R analogue was obtained from l-arabinose. The dipoles were generated in situ from α-arylimino esters of common amino acids (glycine, alanine, or phenylalanine) and aromatic aldehydes (benzaldehyde, 3-formylpyridine and 4-methoxybenzaldehyde). Under optimized conditions, the cycloaddition reactions were highly diastereo- and regioselective to yield, in most of the cases, a very major adduct of the 16 theoretically possible. The diastereoselectivity relies on the strict stereocontrol exerted by the stereogenic center of the pyranone. Thus, the (S)-enone, derived from d-xylose, gave tetrasubstituted pyrrolidines having a defined stereochemistry for the four stereocenters of the ring, while they had the opposite configuration when starting from the (R)-dihydropyranone. Furthermore, some endo-cycloadducts underwent isomerization of the carbons vicinal to the nitrogen atom to afford pyrrolidines with a rather unusual stereochemistry for the direct dipolar cycloadditions.
- Udry, Guillermo A. Oliveira,Repetto, Evangelina,Varela, Oscar
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p. 4992 - 5006
(2014/06/23)
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- Enantioselective copper-catalyzed [3+3] cycloaddition of azomethine ylides with azomethine imines
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The more dipoles, the merrier: An asymmetric [3+3] cycloaddition of azomethine ylides derived from imines 1 with azomethine imines 2 in the presence of a chiral ferrocenylphosphine-copper catalyst afforded highly functionalized heterocyclic products 3 in high yield with excellent enantio- and diastereoselectivity (see scheme; DBU=1,8-diazabicyclo[5.4.0]undec-7-ene). The 1,3-dipolar reaction partners can be readily prepared from aldehydes. Copyright
- Guo, Hongchao,Liu, Honglei,Zhu, Fu-Lin,Na, Risong,Jiang, Hui,Wu, Yang,Zhang, Lei,Li, Zhen,Yu, Hao,Wang, Bo,Xiao, Yumei,Hu, Xiang-Ping,Wang, Min
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supporting information
p. 12641 - 12645
(2013/12/04)
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- Search of antimycobacterial activities in hybrid molecules with benzopyran skeleton
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A series of hybrid molecules (7-9, 12, 13, and 14-18) consisting of chromans and pyrolidines or cyclic amines were prepared either by (3 + 2) cycloaddition of nitrostyrenes and azomethine ylide or by three component reactions of chromanyl aldehydes, acetylenes, and cyclic amines. All the synthesized compounds were evaluated against both avirulent (H37Ra) and virulent (H37Rv) strains of Mycobacterium tuberculosis. Out of all the compounds screened, compounds 16, 17, and 18 were found to be active against the virulent strain M. tubercolosis H37Rv displaying MIC in the range of 6.25-1.56 μg/ml against. Springer Science+Business Media, LLC 2010.
- Tripathi, Rama P.,Bisht, Surendra Singh,Pandey, Vivek Parashar,Pandey, Sarvesh K.,Singh, Shubhra,Sinha, Sudhir Kumar,Chaturvedi, Vinita
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experimental part
p. 1515 - 1522
(2012/06/15)
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- Diversity oriented synthesis of pyrrolidines via natural carbohydrate solid acid catalyst
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Natural carbohydrate scaffold catalyzed diastereoselective synthesis of functionalized pyrrolidines have been developed via 1,3-dipolar cycloaddition of azomethine ylides derived from α-imino esters with dienes or dipolarophiles. Naturally most abundant carbohydrates, like cellulose and starch, were converted into their sulfuric acid derivative, which are exhibiting efficient catalytic properties, along with excellent cost effectivity and recyclability. The advantages of this methodology are diversity oriented metal free synthesis of functionalized pyrrolidines, mild reaction condition, high diasteroselectivity and yield.
- Kumar, Atul,Gupta, Garima,Srivastava, Suman
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experimental part
p. 458 - 462
(2010/09/05)
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- Hepatitis C Virus Inhibitors
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Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 23
(2009/12/02)
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- Epimerization reaction of a substituted vinylcyclopropane catalyzed by ruthenium carbenes: Mechanistic analysis
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A novel ruthenium carbene-catalyzed epimerization of vinylcyclopropanes is reported. The reaction rate strongly depends on the presence of ruthenium ligands in solution. When the first-generation Grubbs catalyst is employed, a 5.3:1 equilibrium ratio of epimers is established quickly, but when a first-generation Hoveyda catalyst is employed, epimerization is observed only if an additional phosphine or nitrogen ligand is added. NMR and kinetic studies suggest that the isomerization reaction occurs through the intermediacy of a ruthenacyclopentene. The observation suggests that cyclopropylmethylidene ruthenium carbenes of synthetic utility may be accessible via ruthenacyclopentenes obtained via other routes.
- Zeng, Xingzhong,Wei, Xudong,Farina, Vittorio,Napolitano, Elio,Xu, Yibo,Zhang, Li,Haddad, Nizar,Yee, Nathan K.,Grinberg, Nelu,Shen, Sherry,Senanayake, Chris H.
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p. 8864 - 8875
(2007/10/03)
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- HEPATITIS C VIRUS INHIBITORS
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Compounds are disclosed having general formula (I), wherein R1, R2, R3, R4, R', B, Y and X are described in the description. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 60
(2010/02/11)
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- Synthesis and in vitro characterization of a tissue-selective fullerene: vectoring C(60)(OH)(16)AMBP to mineralized bone.
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A tissue-vectored bisphosphonate fullerene, C(60)(OH)(16)AMBP [4,4-bisphosphono-2-(polyhydroxyl-1,2-dihydro-1,2-methanofullerene[60]-61-carboxamido)butyric acid], designed to target bone tissue has been synthesized and evaluated in vitro. An amide bisphosphonate addend, in conjunction with multiple hydroxyl groups, confers a strong affinity for the calcium phosphate mineral hydroxyapatite of bone. Constant composition crystal growth studies indicate that C(60)(OH)(16)AMBP reduces hydroxyapatite mineralization by 50% at a concentration of 1 microM, following a non-Langmuirian mechanism. Parallel studies with C(60)(OH)(30) also indicate an affinity for hydroxyapatite, but at a reduced level (28% crystal growth rate reduction at 1 microM) compared with C(60)(OH)(16)AMBP. This study is the first to demonstrate that a fullerene-based material can be successfully targeted to a selected tissue as a step toward the development of such materials for medical purposes, in general.
- Gonzalez, Kelly A,Wilson, Lon J,Wu, Wenju,Nancollas, George H
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p. 1991 - 1997
(2007/10/03)
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- Stereoselective formal [3 + 2] cycloaddition of N-alkylidene glycine ester anions to chiral fischer alkenylcarbene complexes. Asymmetric synthesis of 3,4,5-trisubstituted prolines
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The reaction between N-alkylidene glycine ester enolates, generated from glycine esters aldimines with LDA in THF at low temperature, and chiral alkoxyalkenylcarbene complexes of chromium provided directly 2,4,5-trisubstituted-3-pyrrolidinylcarbene complexes with total exo selectivity and very high syn and facial diastereoselectivity when carbene complexes bearing the (-)-8-phenylmenthyloxy group were employed. Oxidation of the metal carbene moiety followed by basic hydrolysis of the esters afforded enantiomerically highly enriched syn, exo-3,4,5-trisubstituted prolines, whereas acidic hydrolysis of the same functional groups proceeded with epimerization at the α-amino acid center leading to anti,exo-3,4,5-trisubstituted prolines of very high enantiomeric purity as well.
- Merino, Isabel,Santosh Laxmi,Florez, Josefa,Barluenga, Jose,Ezquerra, Jesus,Pedregal, Concepcion
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p. 648 - 655
(2007/10/03)
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- The catalysis and asymmetric induction of chiral reverse micelle: Synthesis of optically active α-amino acids
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Through alkylation of N-benzylideneglycine ethyl ester in chiral reverse micelle, followed by hydrolysis of the resulting products, optically active α-amino acids were synthesized.
- Sun, Peipei,Zhang, Yongmin
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p. 4173 - 4179
(2007/10/03)
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- Latent Inhibitors. Part 5. Latent Inhibition of Dihydrofolate Reductase by a Pteridine-spiro-cyclopropane
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The design of cyclopropane-containing enzyme activated inhibitors of dihydrofolate reductase is presented.The synthesis of two examples, 2-amino-7,8-dihydro-6-hydroxymethylpteridine-7-spirocyclopropan-4(3H)-one and 2,4-diamino-5-(4-chlorophenyl)-6-cyclopropylpyrimidine, is described.Kinetic studies with dihydrofolate reductase from E. coli are presented to show that the former is a time-dependent inhibitor of the enzyme whereas the latter is a typical competitive inhibitor.The results are interpreted with regard to the active site structure of dihydrofolate reductase.
- Haddow, John,Suckling, Colin J.,Wood, Hamish C. S.
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p. 1297 - 1304
(2007/10/02)
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- Acidities of Glycine Schiff Bases and Alkylation of Their Conjugate Bases
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Equilibrium acidities in Me2SO are reported for six ketimines of the type Ph2C=NCH(R)CO2Et and five aldimines, ArCH=NCH(R)CO2Et.Changing R in the ketimine from H to Ph increased the pKa by 2.2 units.This surprising acidity decrease for Ph substitution points to a substantial increase in steric effect, as do the increases in pKa of 3.8 and 4.2 units observed for the replacement of hydrogen by Me and PhCH2, respectively.Phase-transfer alkylation of the Ph2C=NCH2CO2Et ketimine gave over 90 percent of monoalkylate whereas, under similar conditions, the aldimine 4-ClC6H4CH=NCH2CO2Et gave a mixture of mono- and dialkylate.The difference is that the pKa of the monoalkylated aldimine is essentially the same as that of the parent, which leads to rapid equilibration with the parent anion and consequent dialkylation.The rates of alkylation in Me2SO of these parent and monoalkylated anions did not differ greatly, showing that the relative pKHAs of the parent acid and its monoalkyl derivative, rather tham the relative rates of the mono- and dialkylation reactions, is the principal factor that determines the extent of the competition between monoalkylation and dialkylation.
- O'Donnell, Martin J.,Bennett, William D.,Bruder, Willian A.,Jacobsen, William N.,Knuth, Keith,et al.
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p. 8520 - 8525
(2007/10/02)
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- Some Novel Monocyclic cis-β-Lactams from Glycine
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Enamine derivatives (Ia, b) obtained by the condensation of glycine and β-dicarbonyl compounds have been utilised for the stereoselective synthesis of cis-β-lactams.Addition of POCl3 to a mixture of the potassium salts (I), imines (IIa-c and III) and triethylamine gives 3-enamino-2-azetidinones (IV, VI, VII, X and XXI) in 30-40 percent yield.Imines (IId and IIe) prepared from ethyl glycinate hydrochloride and aromatic aldehydes, when subjected to this reaction yield 3-enamino-β-lactams (XIII and XVII) carrying an ester function.The protecting β-dicarbonyl function canbe easily removed with ethanol/HCl to generate the α-amino-β-lactams (V, VIII, XI, XIV, XVIII and XXII) which have been used as the progenitors for the preparation of 3-amido-2-azetidinones.The α-amido-β-lactams (XV and XIX) having an ester function on treatment with 0.1 N NaOH in acetone get converted into the novel α-amido-β-lactams (XVI and XX) carrying a free carboxy function essential for antibacterial activity.
- Sharma, S. D.,Gupta, P. K.
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p. 760 - 764
(2007/10/02)
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