- Structure-based drug design, synthesis and biological assays of P. falciparum Atg3–Atg8 protein–protein interaction inhibitors
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The proteins involved in the autophagy (Atg) pathway have recently been considered promising targets for the development of new antimalarial drugs. In particular, inhibitors of the protein–protein interaction (PPI) between Atg3 and Atg8 of Plasmodium falc
- Villa, Stefania,Legnani, Laura,Colombo, Diego,Gelain, Arianna,Lammi, Carmen,Bongiorno, Daniele,Ilboudo, Denise P.,McGee, Kellen E.,Bosch, Jürgen,Grazioso, Giovanni
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Read Online
- The Bull-James assembly as a chiral auxiliary and shift reagent in kinetic resolution of alkyne amines by the CuAAC reaction
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The Bull-James boronic acid assembly is used simultaneously as a chiral auxiliary for kinetic resolution and as a chiral shift reagent for in situ enantiomeric excess (ee) determination by 1H NMR spectroscopy. Chiral terminal alkyne-containing amines, and their corresponding chiral triazoles formed via CuAAC, were probed in situ. Selectivity factors of up to s = 4 were imparted and measured, accurate to within ±3% when compared to chiral GC.
- Brittain, William D. G.,Chapin, Brette M.,Zhai, Wenlei,Lynch, Vincent M.,Buckley, Benjamin R.,Anslyn, Eric V.,Fossey, John S.
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Read Online
- Base-Promoted Cycloisomerization for the Synthesis of Oxazoles and Imidazoles
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Treatment of propargylamides or propargylamidines with cesium carbonate in DMSO results in the formation of the corresponding oxazoles or imidazoles in good yields. A large variety of substrates with various functional groups are tolerated. DFT study on a model substrate reveals that the reactions proceed via a sequence involving allene formation, intramolecular cyclization, and double-bond isomerization.
- Zhang, Lidan,Xiao, Ke,Qiao, Yan,Li, Xin,Song, Chuanjun,Chang, Junbiao
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supporting information
p. 6913 - 6918
(2018/12/05)
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- Silver-Catalyzed Synthesis of Substituted Pyridine Derivatives from N-Propargylic α-Enamino Esters
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A wide range of substituted pyridine derivatives were synthesized in moderate to good yields from N-propargylic α-enamino esters. The synthetic strategy involved regioselective addition of a propargylamine to the α-carbon atom of an alkynyl ester to produce the N-propargylic α-enamino ester, which acted as the key intermediate in the synthesis.
- Sakthivel, Shanmugam,Sharma, Ashish,Balamurugan, Rengarajan
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supporting information
p. 3941 - 3946
(2017/07/28)
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- Synthesis of 1,2,3-Substituted Pyrroles from Propargylamines via a One-Pot Tandem Enyne Cross Metathesis-Cyclization Reaction
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Enyne cross metathesis of propargylamines with ethyl vinyl ether enables the one-pot synthesis of substituted pyrroles. A series of substituted pyrroles, bearing alkyl, aryl, and heteroaryl substituents, has been synthesized in good yields under microwave irradiation. The reactions are rapid and procedurally simple and also represent a facile entry to the synthetically challenging 1,2,3-substituted pyrroles. The value of the methodology is further corroborated by the conversion of pyrroles into 3-methyl-pyrrolines and the derivatization of the 3-methyl-substituent arising from the metathesis reaction.
- Chachignon, Helene,Scalacci, Nicoloì,Petricci, Elena,Castagnolo, Daniele
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p. 5287 - 5295
(2015/05/27)
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- Cyclobutene formation in PtCl2-catalyzed cycloisomerizations of heteroatom-tethered 1,6-enynes
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Aza(oxa)bicyclo[3.2.0]heptenes are accessed through the PtCl 2-catalyzed cycloisomerizations of heteroatom-tethered 1,6-enynes featuring a terminal alkyne and amide as the solvent. It is shown that the weak coordinating properties of the solven
- Ni, Zhenjie,Giordano, Laurent,Tenaglia, Alphonse
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supporting information
p. 11703 - 11706
(2014/10/15)
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- Facile, selective, and regiocontrolled synthesis of oxazolines and oxazoles mediated by ZnI2 and FeCl3
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An expedient method for a direct approach to the selective and regiocontrolled synthesis of 2-oxazolines and 2-oxazoles mediated by ZnI 2 and FeCl3 is described. A Lewis acid promoted cyclization of acetylenic amide with various func
- Senadi, Gopal Chandru,Hu, Wan-Ping,Hsiao, Jia-Shing,Vandavasi, Jaya Kishore,Chen, Chung-Yu,Wang, Jeh-Jeng
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supporting information
p. 4478 - 4481
(2012/10/30)
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- ALPHA2B AND ALPHA2C AGONISTS
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Described herein are compounds that can be useful as bioactive agents. More specifically, the compounds described herein can be useful as both α2B and α2C adrenergic agonists. Methods of synthesis and administration of the compounds are also disclosed.
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Page/Page column 11
(2009/12/02)
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- The synthesis and structure-activity relationship studies of selective acetyl-CoA carboxylase inhibitors containing 4-(thiazol-5-yl)but-3-yn-2-amino motif: Polar region modifications
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The structure-activity relationship study focused on the polar region of the HTS hit A-80040 (1) producing several series of potent and selective ACC2 inhibitors. The SAR suggests a compact lipophilic pocket that does not tolerate polar and ionic groups.
- Xu, Xiangdong,Weitzberg, Moshe,Keyes, Robert F.,Li, Qun,Wang, Rongqi,Wang, Xiaojun,Zhang, Xiaolin,Frevert, Ernst U.,Camp, Heidi S.,Beutel, Bruce A.,Sham, Hing L.,Gu, Yu Gui
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p. 1803 - 1807
(2007/10/03)
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- Synthesis of enantiomerically pure α-[4-(1-substituted)-1,2,3-triazol-4-yl]-benzylacetamides via microwave-assisted click chemistry: towards new potential antimicrobial agents
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Chiral 1-phenyl-2-propynylamines are important building blocks for the synthesis of antifungal and antiaromatase agents related to bifonazole. In this report, a microwave-assisted Cu(I)-catalyzed 'click chemistry' approach has been employed to easily generate a small library of enantiomerically pure α-[4-(1-substituted)-1,2,3-triazol-4-yl]benzylacetamides starting from racemic propargylamines. These compounds could represent easily accessible intermediates for the synthesis of new antimicrobial agents.
- Castagnolo, Daniele,Dessi, Filippo,Radi, Marco,Botta, Maurizio
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p. 1345 - 1350
(2008/02/10)
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- Ruthenium-catalyzed propargylic substitution reactions of propargylic alcohols with oxygen-, nitrogen-, and phosphorus-centered nucleophiles
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The scope and limitations of the ruthenium-catalyzed propargylic substitution reaction of propargylic alcohols with heteroatom-centered nucleophiles are presented. Oxygen-, nitrogen-, and phosphorus-centered nucleophiles such as alcohols, amines, amides, and phosphine oxide are available for this catalytic reaction. Only the thiolate-bridged diruthenium complexes can work as catalysts for this reaction. Results of some stoichiometric and catalytic reactions indicate that the catalytic propargylic substitution reaction proceeds via an allenylidene complex formed in situ, whereby the attack of nucleophiles to the allenylidene Cγ atom is a key step. Investigation of the relative rate constants for the reaction of propargylic alcohols with several para-substituted anilines reveals that the attack of anilines on the allenylidene Cγ atom is not involved in the rate-determining step and rather the acidity of conjugated anilines of an alkynyl complex, which is formed after the attack of aniline on the C γ atom, is considered to be the most important factor to determine the rate of this catalytic reaction. The key point to promote this catalytic reaction by using the thiolate-bridged diruthenium complexes is considered to be the ease of the ligand exchange step between a vinylidene ligand on the diruthenium complexes and another propargylic alcohol in the catalytic cycle. The reason why only the thiolate-bridged diruthenium complexes promote the ligand exchange step more easily with respect to other monoruthenium complexes in this catalytic reaction should be that one Ru moiety, which is not involved in the allenylidene formation, works as an electron pool or a mobile ligand to another Ru site. The catalytic procedure presented here provides a versatile, direct, and one-step method for propargylic substitution of propargylic alcohols in contrast to the so far well-known stoichiometric and stepwise Nicholas reaction.
- Nishibayashi, Yoshiaki,Milton, Marilyn Daisy,Inada, Youichi,Yoshikawa, Masato,Wakiji, Issei,Hidai, Masanobu,Uemura, Sakae
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p. 1433 - 1451
(2007/10/03)
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- Enantioselective synthesis of 1-aryl-2-propenylamines: A new approach to a stereoselective synthesis of the Taxol side chain
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A variety of substituted 1-aryl-2-propenylamines of high enantiomeric purity were prepared via lipase-catalysed resolution of the corresponding racemates. (R)-1-Phenyl-2-propenylamine was further synthesised into (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoic acid methyl ester, the side chain of Taxol.
- Castagnolo, Daniele,Armaroli, Silvia,Corelli, Federico,Botta, Maurizio
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p. 941 - 949
(2007/10/03)
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- Carbene-carbene interconversion between 1- and 3-phenyl-2-propynylidenes
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1-Phenyl-3-diazopropyne (1d) and 3-phenyl-3-diazopropyne (2d) were prepared and photolyzed under various conditions. In ethanol at ambient temperatures, both 1d and 2d gave a 1:10 ± 1 mixture of 1-phenyl-3-ethoxypropyne (3) and 3-phenyl-3-ethoxypropyne (4). The photolyses of matrix-isolated 1d and 2d at cryogenic temperatures were followed by EPR, IR, and UV-visible spectroscopy. EPR experiments in 2-methyltetrahydrofuran (MTHF), isopentane, and ethanol-d6 matrices at 9 K showed spectra due to a mixture of the corresponding triplet carbenes 1c (D/hc = 0.543 and |E/hc| = 0.003 cm-1) and 2c (D/hc = 0.526 and |E/hc| = 0.010 cm-1). The ratio of the generated carbenes carried the memory of the starting diazo compounds; 1c and 2c were produced mainly from 1d and 2d, respectively. Carbene 2c isomerized to 1c at 70-90 K in MTHF and ethanol-d6 and at 44-68 K in isopentane, indicating that 1c was thermodynamically more stable than 2c on the triplet ground-state potential energy surface. IR and UV-visible absorption experiments employing various media (argon, isopentane, N2, CO/Ar, O2/N2, and O2/Ar) revealed that the photolysis of 2d afforded mostly absorptions due to 2c. Photolysis of 1d produced similar spectra, due mainly to 2c, together with weak absorptions due to 1c. The different results observed in EPR and IR experiments were explained by the difference in the matrices in which the diazo groups were photolyzed. Calculations at the ab initio MP2/DZV(d) level of theory showed that the triplet ground state of 1c was more thermodynamically stable than 2c by 1.41 kcal/mol, in agreement with the experimental results. The situation is reversed in the singlet manifold, where 2c was computed to be much lower in energy than 1c. The energy differences (ΔEST) between the singlet and triplet states were computed to be 15.7 and 11.0 kcal/mol for 1c and 2c, respectively, with the DZV(d) basis set.
- Noro, Masaki,Masuda, Takeshi,Ichimura, Andrew S.,Koga, Noboru,Iwamura, Hiizu
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p. 6179 - 6190
(2007/10/02)
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- Base-Catalyzed Cyclization of N-Propargylamides to Oxazoles
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The base-catalyzed cyclization of some N-propargylamides to oxazoles has been studied in the presence of sodium hydride and potassium carbonate.The α-arylsubstituted propargylamides 1c-d (Ar = p-OMeC6H4 (1c), C6H5 (1d), and p-O2NC6H4 (1e)) cyclized with markedly higher rates (1e > 1d > 1c) than the unsubstituted and α-methyl substituted propargylamides 1a and 1b.A 1H nmr spectroscopic experiment demonstrated the presence of an allenic intermediate in the potassium carbonate-catalyzed ring closure of 1e.The observed rank order of reactivities correlates well withthe acidities of the respective propargylic hydrogens of the amides and with the ability of the ring closed intermediates to stabilize an oxazole anion.The results demonstrate that the base-catalyzed formation of oxazoles from propargylamides may proceed via an allenic intermediate.
- Nilsson, Bjoern M.,Hacksell, Uli
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p. 269 - 275
(2007/10/02)
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