- Helical chirality induction in zinc bilindiones by amino acid esters and amines
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Complexation of α-amino acid esters, β-amino ethers, and amines with a series of zinc 1,19-bilindione derivatives was studied, particularly focusing on the helical chirality induction in the bilindione framework triggered by the binding of chiral guests. Comparative studies of binding and helical chirality induction indicated that binding and chiral induction were markedly affected by polar substituents present in both zinc bilindiones and guests. 2-Hydroxyethyl groups at the 2,18-positions of zinc bilindione largely assisted the binding of amines and amino acid esters but not the chiral induction. 19O-Alkylation of the zinc bilindiones had inhibitory effects on the binding but enhanced efficiency of helical chirality induction. The enantiomeric excess of 19O-alkyl zinc bilindione complexed with L-Trp-OMe in CD2Cl2 was 73% at 223 K. A COOR group and an aromatic group in the guest promoted helical chirality induction of 19O-alkylated zinc bilindiones. The patterns of 1H NMR complexation-induced shifts of zinc bilindiones and guests and a molecular modeling study of the complexes showed that electrostatic repulsion between the COOR group of amino acid esters and the lactam ring of zinc bilindiones, and stacking of the side chain groups of amino acid esters on the C ring of zinc bilindione made a significant contribution to efficient helical chirality induction.
- Mizutani, Tadashi,Yagi, Shigeyuki,Honmaru, Atsushi,Murakami, Shinji,Furusyo, Masaru,Takagishi, Toru,Ogoshi, Hisanobu
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- Design, synthesis, and characterization of novel aminoalcohol quinolines with strong in vitro antimalarial activity
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Malaria is the fifth most lethal parasitic infections in the world. Herein, five new series of aminoalcohol quinolines including fifty-two compounds were designed, synthesized and evaluated in vitro against Pf3D7 and PfW2 strains. Among them, fourteen displayed IC50 values below or near of 50.0 nM whatever the strain with selectivity index often superior to 100.17b was found as a promising antimalarial candidate with IC50 values of 14.9 nM and 11.0 nM against respectively Pf3D7 and PfW2 and a selectivity index higher than 770 whatever the cell line is. Further experiments were achieved to confirm the safety and to establish the preliminary ADMET profile of compound 17b before the in vivo study performed on a mouse model of P. berghei ANKA infection. The overall data of this study allowed to establish new structure-activity relationships and the development of novel agents with improved pharmacokinetic properties.
- Dassonville-Klimpt,Schneider,Damiani,Tisnerat,Cohen,Azas,Marchivie,Guillon,Mullié,Agnamey,Totet, Anne,Dormoi,Taudon,Pradines,Sonnet
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- NOVEL AMINOPYRIDINEMETHANOL COMPOUNDS AND THEIR USE
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The present invention is directed to novel compounds of Formula (I): pharmaceutically acceptable salts or solvates thereof, and their use, in particular in the treatment or prevention of malaria.
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- Palladium-N-heterocyclic carbene (NHC)-catalyzed asymmetric synthesis of indolines through regiodivergent C(sp3)-H activation: Scope and DFT study
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Two bulky, chiral, monodentate N-heterocyclic carbene ligands were applied to palladium-catalyzed asymmetric C-H arylation to incorporate C(sp3)-H bond activation. Racemic mixtures of the carbamate starting materials underwent regiodivergent reactions to afford different trans-2,3- substituted indolines. Although this CAr-Calkyl coupling requires high temperatures (140-160°C), chiral induction is high. This regiodivergent reaction, when carried out with enantiopure starting materials, can lead to single structurally different enantiopure products, depending on the catalyst chirality. The C-H activation at a tertiary center was realized only in the case of a cyclopropyl group. No C-H activation takes place alpha to a tertiary center. A detailed DFT study is included and analyses of methyl versus methylene versus methine C-H activation is used to rationalize experimentally observed regio- and enantioselectivities.
- Katayev, Dmitry,Larionov, Evgeny,Nakanishi, Masafumi,Besnard, Cline,Kündig, E. Peter
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p. 15021 - 15030
(2015/02/19)
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- First syntheses of lorneic acids A and B with potential PDE5 inhibition activity
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Two natural products with potential PDE5 inhibition activity, lorneic acids A and B, have been synthesized for the first time in high yield using a chiral amide stereocontrolled addition of aryl lithium to aldehyde as the key step, and the configuration of the chiral benzylic alcohol in lorneic acid B was determined to be S. Georg Thieme Verlag Stuttgart · New York.
- Ma, Xiang,Song, Yuting,Liu, Hao,Chen, Ruijiao,Chen, Xiaochuan
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scheme or table
p. 607 - 610
(2012/03/27)
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- The dinosyl group: A powerful activator for the regioselective alcoholysis of aziridines
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The N-2,4-dinitrophenylsulfonyl group (dinosyl, DNs) was found to be an excellent choice for the N-activation of aziridines towards ring cleavage with primary, secondary, andsterically demanding tertiary alcohols. Alcoholysis does not need any additional
- Stanetty, Christian,Blaukopf, Markus K.,Lachmann, Bodo,Noe, Christian R.
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p. 3126 - 3130
(2011/07/08)
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- METHODS AND COMPOSITIONS FOR TREATING AMYLOID-RELATED DISEASES
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Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease.
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- Method for the preparation of optically active 2-aryl alkyl aldehydes and formation of 2-aryl-alkanoic acids therefrom
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The present process is directed to preparing optically active 2-aryl alkyl aldehydes by various processes through the use of an optically active amine, (-)-2'-amino-3-phenyl propane. The aldehyde formed can then be oxidized to produce the corresponding ac
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- Certain sulfonamide heterobicyclic platelet activating factor antagonists
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Compounds of general formula I; STR1 wherein: A1 is =N--, =CH-- or =CR1 --; A2 is =N--, =CH-- or =CR2 --; provided that, when one of A1 and A2 is a nitrogen atom, the other of A1 and A2 is other than a nitrogen atom; wherein the other variables are as defined in the specification and their pharmaceutically and veterinarily acceptable acid addition salts and hydrates are antagonists of platelet activating factor (PAF) and as such are useful in the treatment or amelioration of various diseases or disorders mediated by PAF.
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- Asymmetric Synthesis of Optically Active Phthalides via ortho-Lithiation and Cyclization of Chiral N-Monosubstituted Benzamides
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The chiral N-monosubstituted benzamides 1a-d, derived from (S)-(-)-α-phenylethylamine and L--(-)-phenylalanine, gave the ortho-lithiated species on treatment with butyllithium (2.2 equiv.) and TMEDA in THF at 0 deg C.The resulting lithio amides reacted smoothly with aldehydes to afford the expected ortho substituted products 2a-d as diastereoisomeric mixzures, which were converted quantitatively into the phthalides 3a, b on acidic hydrolysis.Use of (S)-(-)-N-benzoyl-O-methylphenylalaninol 1c and (S)-(-)-N-(3-methoxybenzoyl)-O-methylphenylalaninol 1d as the amide resulted in consistently high diastereoselectivities.The reaction of the dianions derived from 1c with valeraldehyde gave, after cyclization, (S)-(-)-3-butylphthalide, an essential oil of celery, with 83 percent e.e.
- Matsui, Syuichi,Uejima, Akinori,Suzuki, Yoshinori,Tanaka, Kazuhiko
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p. 701 - 704
(2007/10/02)
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- Improvement in the Enantioselectivity of the Hydrogen Transfer with NADH Models Bearing Amino Alcohols as Chiral Auxiliaries
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Chiral amino alcohols have been linked to the γ-carbonyl group of the 5,7-dihydrothienopyridines (4a-d).These models are much more easily handled in mild conditions than common NADH models.The factors affecting enantiomeric excess have been studied, e.g. influence of temperature, polarity of solvents, magnesium concentration, and hydrogen bonding.By appropriate modifications of the chiral auxiliary, the rigidity of the ternary complex: model-Mg2+-substrate involved has been enhanced.In this way a high enantiomeric excess has been obtained.
- Cazin, Jacques,Duflos, Jack,Dupas, Georges,Bourguignon, Jean,Queguiner, Guy
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p. 867 - 872
(2007/10/02)
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- Synthesis, Regioselective Deprotonation, and Stereoselective Alkylation of Fluoro Ketimines
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Fluoroacetone imines of cyclohexylamine, valinol O-methyl ether, and phenylalaninol O-methyl ether and 2-fluorocyclohexanone imines of cyclohexylamine and phenylalaninol O-methyl ether were prepared.The temperature-dependent, regioselective deprotonation of these imines was employed in highly regioselective alkylation reactions.The deprotonation of fluoroacetone cyclohexylimine on the carbon bearing fluorine yielded only a single stereoisomer as determined by low temperature 19F NMR.In contrast, deprotonation of fluoroacetone O-benzyloximes was not regiospecific under any of the conditions examined.
- Welch, John T.,Seper, Karl W.
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p. 2991 - 2999
(2007/10/02)
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- Asymmetric Induction Reactions. I. Asymmetric Sigmatropic Rearrangements of Sulfur Ylides Derived from Chiral Ketenimines and Trimethylsulfonium Ylide
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The asymmetric (2,3) sigmatropic rearrangements of 2-alkylamino-3-phenyl-2-pentenyl-methylsulfonium methylides were accomplished by the reaction of ethylphenylketenimines 3 having a chiral carbon next to the nitrogen atom with trimethylsulfonium ylide, and acidic hydrolysis of the imines 4 thus obtained led to optically active 3-methylthiomethyl-3-phenyl-2-pentanone (5).The reaction of ethylphenylketene (-)-menthylimine (3g) with trimethylsulfonium ylide at -78 deg C resulted in the highest optical yield of (R)-(-)-5 in the above sequence.Keywords--asymmetric induction; (2,3) sigmatropic rearrangement; chiral ketenimine; sulfur ylide; trimethylsulfonium ylide
- Hiroi, Kunio,Sato, Shuko
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p. 2331 - 2338
(2007/10/02)
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- ASYMMETRIC CONJUGATE ADDITION OF COPPER AZAENOLATES AS SYNTHETIC EQUIVALENT OF ENOLATES TO CYCLIC ENONES
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Asymmetric conjugate addition to prochiral cyclic enones was devised by using copper azaenolates derived from an acetone imine of optically active amino ethers which were prepared from α-amino acids, the optical yields of the resulting 3-acetonylcycloalkanones being found to attain as high as 75percent e.e.
- Yamamoto, Keiji,Iijima, Masayuki,Ogimura, Yoshinobu
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p. 3711 - 3714
(2007/10/02)
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