- Asymmetric construction of dihydrobenzofuran-2,5-dione derivatives via desymmetrization of p-quinols with azlactones
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The desymmetrization of p-quinols through a chiral bisguanidinium hemisalt catalyzed enantioselective Michael addition/lactonization cascade reaction with azlactones was reported. 3-Amino-benzofuran-2,5-diones containing a chiral amino acid residue were achieved with up to 99% ee and >19?:?1 dr. An exploration of the structure of the catalyst bisguanidinium was undertaken, revealing a bifunctional catalytic model.
- Xie, Lihua,Dong, Shunxi,Zhang, Qian,Feng, Xiaoming,Liu, Xiaohua
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supporting information
p. 87 - 90
(2019/01/03)
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- Metal-Free Insertion Reactions of Diazo Carbonyls to Azlactones
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Insertion reactions of diazo carbonyls to azlactones in basic conditions have been performed. The developed method allows the preparation of a wide range of oxazole derivatives in yields ranging from 74 to 98%. Different substituents on both azlactone rings and diazo carbonyls do not compromise the methodology, even those containing stereogenic centers. Isotopic labeling experiments revealed the mechanism may proceed through a rare diazo carbonyl activation by an ammonium salt derivative.
- De Mello, Amanda C.,Momo, Patrícia B.,Burtoloso, Antonio C. B.,Amarante, Giovanni W.
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p. 11399 - 11406
(2018/09/12)
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- Group-Assisted Purification Chemistry for Asymmetric Mannich-type Reaction of Chiral N-Phosphonyl Imines with Azlactones Leading to Syntheses of α-Quaternary α,β-Diamino Acid Derivatives ?
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An asymmetric Mannich-type reaction between chiral N-phosphonyl imines and azlactones [oxazol-5(4H)-ones] has been established under convenient conditions at room temperature. The reaction was performed without using any bases, additives, or catalysts to achieve up to excellent chemical yields and diastereoselectivity for 32 examples. The α-quaternary syn-α,β-diamino acid products were purified simply by washing the crude mixtures with cosolvents, following the group-assisted purification chemistry/technology, without involving traditional chromatography or recrystallization methods. The auxiliary can be readily removed and recycled for reuse. The absolute configuration was unambiguously assigned by X-ray structural analysis.
- Zhang, Haowei,Yang, Zhen,Zhao, Brian Nlong,Li, Guigen
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p. 644 - 655
(2018/01/27)
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- STRUCTURE AND SYNTHESIS OF HIGHLY FLUORINATED AMINO ACID DERIVATIVES
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Methods of synthesizing polyfluorinated amino acid derivatives are disclosed, along with polyfluorinated amino acid derivatives produced from said methods, as well as compositions containing same. The synthesis methods utilize an oxazolone and a perfluoroarene to produce the polyfluorinated amino acid derivatives.
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Paragraph 0170; 0171; 0172; 0176
(2018/09/19)
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- Polyfluoroarylation of oxazolones: Access to non-natural fluorinated amino acids
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Herein, conditions are provided for the formation and use of the oxazolone enolate for the nucleophilic substitution of highly fluorinated (hetero)arenes, which after unmasking yield highly fluorinated non-natural amino acids and derivatives. In addition, the properties and chemical behavior of this new class of amino acids are explored. The utility is demonstrated in the one pot synthesis of medicinally relevant 2-aminohydantoins.
- Teegardin, Kip A.,Weaver, Jimmie D.
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supporting information
p. 4771 - 4774
(2017/07/06)
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- Enantioselective construction of tetrasubstituted stereogenic carbons through bronsted base catalyzed michael reactions: α′-hydroxy enones as key enoate equivalent
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Catalytic and asymmetric Michael reactions constitute very powerful tools for the construction of new C-C bonds in synthesis, but most of the reports claiming high selectivity are limited to some specific combinations of nucleophile/electrophile compound types, and only few successful methods deal with the generation of all-carbon quaternary stereocenters. A contribution to solve this gap is presented here based on chiral bifunctional Bronsted base (BB) catalysis and the use of α′-oxy enones as enabling Michael acceptors with ambivalent H-bond acceptor/donor character, a yet unreported design element for bidentate enoate equivalents. It is found that the Michael addition of a range of enolizable carbonyl compounds that have previously demonstrated challenging (i.e., α-substituted 2-oxindoles, cyanoesters, oxazolones, thiazolones, and azlactones) to α′-oxy enones can afford the corresponding tetrasubstituted carbon stereocenters in high diastereo- and enantioselectivity in the presence of standard BB catalysts. Experiments show that the α′-oxy ketone moiety plays a key role in the above realizations, as parallel reactions under identical conditions but using the parent α,β-unsaturated ketones or esters instead proceed sluggish and/or with poor stereoselectivity. A series of trivial chemical manipulations of the ketol moiety in adducts can produce the corresponding carboxy, aldehyde, and ketone compounds under very mild conditions, giving access to a variety of enantioenriched densely functionalized building blocks containing a fully substituted carbon stereocenter. A computational investigation to rationalize the mode of substrate activation and the reaction stereochemistry is also provided, and the proposed models are compared with related systems in the literature.
- Badiola, Eider,Fiser, Bla,Gmez-Bengoa, Enrique,Mielgo, Antonia,Olaizola, Iurre,Urruzuno, Iaki,Garca, Jess M.,Odriozola, Jos M.,Razkin, Jess,Oiarbide, Mikel,Palomo, Claudio
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supporting information
p. 17869 - 17881
(2015/02/19)
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- Peptide-catalyzed conversion of racemic oxazol-5(4 H)-ones into enantiomerically enriched α-amino acid derivatives
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We report the development and optimization of a tetrapeptide that catalyzes the methanolytic dynamic kinetic resolution of oxazol-5(4H)-ones (azlactones) with high levels of enantioinduction. Oxazolones possessing benzylic-type substituents were found to perform better than others, providing methyl ester products in 88:12 to 98:2 er. The mechanism of this peptide-catalyzed process was investigated through truncation studies and competition experiments. High-field NOESY analysis was performed to elucidate the solution-phase structure of the peptide, and we present a plausible model for catalysis.
- Metrano, Anthony J.,Miller, Scott J.
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p. 1542 - 1554
(2014/03/21)
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- Alkynyliodonium salt mediated alkynylation of azlactones: Fast access to Cα-tetrasubstituted α-amino acid derivatives
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An efficient electrophilic alkynylation of azlactones (oxazol-5(4H)-ones) is developed using alkynyl(phenyl)iodonium salts as the electrophilic alkyne source. After remarkably short reaction times, the desired alkyne functionalized azlactones are obtained in 60-97% yield and can be transformed easily into a variety of quaternary α-amino acid derivatives.
- Finkbeiner, Peter,Weckenmann, Nicole M.,Nachtsheim, Boris J.
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supporting information
p. 1326 - 1329
(2014/04/03)
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- Organocatalyzed asymmetric 1,4-addition of azlactones to α,β-unsaturated trichloromethyl ketones: Synthesis of α,α-disubstituted α-amino acid derivatives
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The first asymmetric 1,4-addition of azlactones to α,β-unsaturated trichloromethyl ketones catalyzed by cinchona alkaloid derived bifunctional thiourea catalysts was developed. A series of α,α-disubstituted α-amino acid derivatives bearing a quaternary stereocenter at the α-position were obtained in high yields with excellent diastereo- and enantioselectivities (up to -20:1 dr and 99% ee). In addition, the trichloromethyl moiety in these adducts was identified as a good leaving group.
- Zhang, Jinlong,Liu, Xihong,Wu, Chongyang,Zhang, Panpan,Chen, Jianbo,Wang, Rui
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supporting information
p. 7104 - 7108
(2015/01/16)
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- One-pot preparation of oxazol-5(4H)-ones from amino acids in aqueous solvents
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A method for one-pot synthesis of oxazol-5(4H)-ones has been developed using 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), which is available for the activation of carboxylic acids in an aqueous solvent. The oxazolones were prepared by the TV-acylation of amino acids with carboxylic acids and the subsequent cyclodehydration of the resulting N-acylamino acids by the addition of N,N-diethylaniline. Since both these reactions proceed effectively with the same coupling reagent, DMT-MM, in aqueous solvents, the procedure is simplified and becomes easy to perform. In addition, 5-(triazinyloxy)oxazole derivatives have been synthesized by controlling the basicity of the reaction system.
- Fujita, Hikaru,Kunishima, Munetaka
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experimental part
p. 907 - 912
(2012/08/08)
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- One-pot synthesis of 2,4,5-trisubstituted oxazoles from N-acyl amino acids by a combination of cyclodehydration with N,N′-diisopropylcarbodiimide and Wittig olefination
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By a combination of cyclodehydration of N-acyl amino acids with N,N′-diisopropylcarbodiimide (DIC) and non-classical Wittig olefination of the resultant 5(4H)-oxazolones with Ph3PCHCN and Ph 3PCHCOOEt, 5-oxazoleacetonitriles and 5-oxazoleacetates were synthesized in one-pot in 41-85% and 57-70% yields, respectively.
- Huang, Wenhua,Dong, Guangping,Mijiti, Zumureti
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experimental part
p. 977 - 981
(2012/02/13)
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- Polyclonal antibodies: A cheap and efficient tool for screening of enantioselective catalysts
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Enantioselective polyclonal antibodies have been produced and characterized to develop a high-throughput screening method for lipase activity fingerprinting, with a view to the enantioselective hydrolysis of azlactones.
- MacOvei, Cristian,Vicennati, Paola,Quinton, Julia,Nevers, Marie-Claire,Volland, Herve,Creminon, Christophe,Taran, Frederic
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supporting information; experimental part
p. 4411 - 4413
(2012/05/20)
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- Enantioselective quaternization of 4-substituted oxazol-5-(4H)-ones using recoverable Cinchona-derived dimeric ammonium salts as phase-transfer organocatalysts
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Dimeric anthracenyldimethyl-derived Cinchona ammonium salts are used as chiral organocatalysts (5 mol %) for the enantioselective 4-alkylation of 4-substituted azlactones. The corresponding adducts bearing a new quaternary center were obtained with up to
- Tari, Silvia,Avila, Angel,Chinchilla, Rafael,Najera, Carmen
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experimental part
p. 176 - 180
(2012/05/20)
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- Dynamic kinetic resolution of N-benzoyl-DL-amino acids via peptide bond forming reactions
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Dynamic kinetic resolution (DKR) was demonstrated in the carbodiimide-mediated couplings of N-benzoyl-DL-amino acids with L-amino acid esters: the yields of the D-L-peptides significantly exceeded 50% in some cases. N-benzoyl-DL-t-leucine afforded the D-L-peptide almost exclusively (up to 96% yield) in the reaction with methyl L-prolinate, which is the most efficient DKR obtained in the field of amino acids and derivatives.
- Miyazawa, Toshifumi,Hamada, Takashi
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body text
p. 419 - 422
(2011/12/04)
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- A new method proposed for the determination of absolute configurations of α-amino acids
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Enantiopure α-amino acids were converted to 4-substituted 2-aryl- and 2-alkyl-5(4H)-oxazolones under partial racemization. These nonracemic mixtures were dissolved in CDCl3, an equimolar amount of the chiral dirhodium complex Rh2(II)[(R)-(+)-MTPA]4 (MTPA-H = Mosher's acid) was added, and the 1H NMR spectra of the resulting samples were recorded [dirhodium method). The relative intensities of 1H signals dispersed by the formation of diastereomeric adducts allow to determine the absolute configuration (AC) of the starting a-amino acids. Binding atoms in the adducts were identified by comparing the 1H and 13C chemical shifts of the oxazolones in the absence and presence of Rh2(II)[(R)-(+)- MTPA]4. Thereby, information about the scope and limits of this method can be extracted. A protocol how to use this method is presented. Copyright
- Gomez, Edison Diaz,Duddeck, Helmut
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experimental part
p. 222 - 227
(2010/02/28)
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- Highly efficient dynamic kinetic resolution of azlactones by urea-based bifunctional organocatalysts
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Novel tasks for a venerable molecule: Bifunctional organocatalysts of the type shown, with a quasi Lewis acidic urea or thiourea unit and a Bronsted basic amine functionality, effect the dynamic kinetic resolution of azlactones with high enantioselectivit
- Berkessel, Albrecht,Cleemann, Felix,Mukherjee, Santanu,Mueller, Thomas N.,Lex, Johann
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p. 807 - 811
(2007/10/03)
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- Enantiomerically enriched alpha , alpha -distributed amino acids and method
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Compositions and methods for the preparation of enantiomerically enriched alpha , alpha -disubstituted amino acid precursors are presented. Briefly, allylic electrophiles are alkylated with oxazolones in the presence of a base and catalytic quantities of
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- An efficient strategy to orthogonally protected (R)- and (S)-α-methyl(alkyl)serine-containing peptides via a novel azlactone/oxazoline interconversion reaction
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A novel strategy for the synthesis of (R)- and (S)-α-methyl(alkyl)serine-containing peptides is presented. Using (S)-phenylalanine cyclohexylamide 6 as chiral auxiliary, the optically pure azlactones (R)- and (S)-2 were synthesized via a novel azlactone/oxazoline interconversion reaction (Figures 3 and 6). These azlactones constitute fully protected and activated synthetic equivalents of (R)- and (S)-α-methylserine and can be directly incorporated into peptides without further protective group manipulations. Like other α,α-dialkylated glycines, optically pure α-alkylserines can be used to stabilize β-turn and α-helical conformations in short peptides.
- Obrecht, Daniel,Altorfer, Michael,Lehmann, Christian,Sch?nholzer, Peter,Müller, Klaus
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p. 4080 - 4086
(2007/10/03)
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- A reinvestigation of the α-alkylation of 4-monosubstituted 2-phenyloxazol-5(4H)-ones ('azlactones'): A general entry into highly functionalized α,α-disubstituted α-amino acids
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Novel, more reliable and general reaction conditions for the α-alkylation of 4-monosubstituted 2-phenyloxazol-5(4H)-ones (= 4-monosubstituted 2-phenyl-azlactones) rac-2 to 4,4-disubstituted 2-phenyloxazol-5(4H)-ones rac-1 were found. Thus, a whole range of highly functionalized rac-1 were prepared in medium-to-good overall yields (40-90%). Azlactones rac-1 are ideal precursors for the synthesis of optically pure α,α-disubstituted (R)- and (S)-α-amino acids.
- Obrecht,Bohdal,Ruffieux,Muller
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p. 1423 - 1429
(2007/10/02)
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- STUDIES ON THE KINETICS OF RACEMIZATION OF 2,4-DISUBSTITUTED-5(4H)-OXAZOLONES
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The kinetics of racemization of 2,4-disubstituted-5(4H)-oxazolones obtained from N-acetyl, N-benzoyl, and N-benzyloxycarbonylglycyl-L-leucine, -valine, and -phenylalanine have been studied in several solvents alone and in the presence of tertiary amines.T
- Slebioda, Marek,St-Amand, Marc A.,Chen, Francis M. F.,Benoiton, N. Leo
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p. 2540 - 2544
(2007/10/02)
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- ETUDE DE LA RACEMISATION INDUITE PAR LA DMAP DANS LES REACTIONS DE COUPLAGE PEPTIDIQUE
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The scope and limitation for the use of 4-dimethyalmino pyridine (DMAP) as additive to carbodiimides in peptide synthesis are studied and compared with the results obtained with N-hydroxybenzotriazole (HOBt).The activation of N-acylated aminoacids by the
- Gamet, Jean-Paul,Jacquier, Robert,Verducci, Jean
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p. 1995 - 2002
(2007/10/02)
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- Gas chromatography and mass spectrometry of derivatives of amino acids. Oxazolin-5-ones of several acyl-leucines.
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By the action of dicyclohexylcarbodiimide on fourteen different acyl-leucines in ethyl acetate solution, the corresponding oxazolin-5-ones were formed. The reaction was quantitative and very rapid. The oxazolin-5-ones were separated on a gas chromatograph on OV-7 and EGA columns. The mass spectra of the oxazolin-5-ones showed characteristic fragments that could be used for identification.
- Grahl-Nielsen,Solheim
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p. 89 - 94,90,92,93
(2007/10/07)
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