- Synthesis of optically active α-methylamino acids and amides through biocatalytic kinetic resolution of amides
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Catalyzed by Rhodococcus sp. AJ270, a nitrile hydratase and amidase containing microbial whole-cell catalyst, under very mild conditions, a number of racemic α-methylamino amides were resolved into the corresponding optically active (S)-(+)-α-methylamino acids and (R)-(-)-α- methylamino amides. The steric requirement of the amidase against α-amino phenylacetamides bearing methyl group(s) at α-amino nitrogen and/or α-carbon was also studied. Coupled with the chemical hydrolysis of amide, the biotransformation process provided a direct synthesis of α-methylamino acids in both enantiomeric forms from readily available racemic amides.
- Wang, Mei-Xiang,Liu, Jun,Wang, De-Xian,Zheng, Qi-Yu
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Read Online
- Asymmetric α-arylation of amino acids
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Quaternary amino acids, in which the α-carbon that bears the amino and carboxyl groups also carries two carbon substituents, have an important role as modifiers of peptide conformation and bioactivity and as precursors of medicinally important compounds1,2. In contrast to enantioselective alkylation at this α-carbon, for which there are several methods3–8, general enantioselective introduction of an aryl substituent at the α-carbon is synthetically challenging9. Nonetheless, the resultant α-aryl amino acids and their derivatives are valuable precursors to bioactive molecules10,11. Here we describe the synthesis of quaternary α-aryl amino acids from enantiopure amino acid precursors by α-arylation without loss of stereochemical integrity. Our approach relies on the temporary formation of a second stereogenic centre in an N′-arylurea adduct12 of an imidazolidinone derivative6 of the precursor amino acid, and uses readily available enantiopure amino acids both as a precursor and as a source of asymmetry. It avoids the use of valuable transition metals, and enables arylation with electron-rich, electron-poor and heterocyclic substituents. Either enantiomer of the product can be formed from a single amino acid precursor. The method is practical and scalable, and provides the opportunity to produce α-arylated quaternary amino acids in multi-gram quantities.
- Leonard, Daniel J.,Ward, John W.,Clayden, Jonathan
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p. 105 - 109
(2018/10/15)
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- Asymmetric α-arylation of amino acids
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Quaternary amino acids, in which the α-carbon that bears the amino and carboxyl groups also carries two carbon substituents, have an important role as modifiers of peptide conformation and bioactivity and as precursors of medicinally important compounds1,2. In contrast to enantioselective alkylation at this α-carbon, for which there are several methods3–8, general enantioselective introduction of an aryl substituent at the α-carbon is synthetically challenging9. Nonetheless, the resultant α-aryl amino acids and their derivatives are valuable precursors to bioactive molecules10,11. Here we describe the synthesis of quaternary α-aryl amino acids from enantiopure amino acid precursors by α-arylation without loss of stereochemical integrity. Our approach relies on the temporary formation of a second stereogenic centre in an N′-arylurea adduct12 of an imidazolidinone derivative6 of the precursor amino acid, and uses readily available enantiopure amino acids both as a precursor and as a source of asymmetry. It avoids the use of valuable transition metals, and enables arylation with electron-rich, electron-poor and heterocyclic substituents. Either enantiomer of the product can be formed from a single amino acid precursor. The method is practical and scalable, and provides the opportunity to produce α-arylated quaternary amino acids in multi-gram quantities.
- Leonard, Daniel J.,Ward, John W.,Clayden, Jonathan
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p. 105 - 109
(2019/10/21)
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- UNNATURAL AMINO ACIDS
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The present invention relates to a process for the preparation compounds of Formula (I): Formula (I) wherein X, Z, Q, Ar, R1, R2, R3 and R4 are each as defined herein. The present invention also relates to processes for the preparation of the compounds of quaternary amino acids and hydantions, to compound of Formula(I), to intermediate compounds of Formula (II), to quaternary amino acid compounds of Formula (III) and to hydantoin compounds of Formula (IV).
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Paragraph 00190; 00296
(2018/07/05)
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- Nitrilases
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The invention relates to nitrilases and to nucleic acids encoding the nitrilases. In addition, methods of designing new nitrilases and methods of use thereof are also provided. The nitrilases have increased activity and stability at increased pH and temperature.
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Paragraph 0263-0264
(2015/09/22)
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- Nitrilases, nucleic acids encoding them and methods for making and using them
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The invention relates to nitrilases and to nucleic acids encoding the nitrilases. In addition methods of designing new nitrilases and method of use thereof are also provided. The nitrilases have increased activity and stability at increased pH and temperature.
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Page/Page column 52
(2016/01/09)
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- Mitsunobu approach to the synthesis of optically active α,α-disubstituted amino acids
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Chiral tertiary α-hydroxy esters of known stereochemical configuration were transformed to α-azido esters by Mitsunobu reaction with HN3. Optimization of this reaction was shown to proceed at room temperature with high chemical yield using 1,1-(azodicarbonyl)dipiperidine (ADDP) and trimethylphosphine (PMe3). Complete inversion of configuration was observed at the α-carbon. Several α,α- disubstituted amino acids were synthesized in high overall chemical yield and optical purity.
- Green, Jonathan E.,Bender, David M.,Jackson, Stona,O'donnell, Martin J.,Mccarthy, James R.
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supporting information; experimental part
p. 807 - 810
(2009/08/08)
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- Asymmetric Strecker reaction of ketoimines catalyzed by a novel chiral bifunctional N,N′-dioxide
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A novel bifunctional N,N′-dioxide derived from L-prolinamide was employed to catalyze the enantioselective Strecker reaction of a range of N-tosyl ketoimines, and an effective additive was used to improve the reactivity (up to 99% yield) as well as the en
- Huang, Xiao,Huang, Jinglun,Wen, Yuehong,Feng, Xiaoming
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p. 2579 - 2584
(2007/10/03)
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- Chiral (s- or r-methylphenylglycine) amino acid crystal and method for preparing same
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The invention concerns chiral amino acid, is preparation method, and the use of said chiral amino acid as intermediate for the synthesis of chiral organic compounds.
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Page column 8; 9
(2008/06/13)
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- Method for preparing chiral amino acids
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The invention concerns a novel method for preparing chiral amino acids of formula (I) characterised in that it consists in contracting a racemic hydantoin of formula (II) with an enantiomeric splitting agent.
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Page column 11
(2008/06/13)
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- Efficient biocatalytic synthesis of highly enantiopure α-alkylated arylglycines and amides
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A number of racemic α-alkylarylglycine amides including 1-amino-1-carbamoyl-1,2,3,4-tetrahydronaphthalene underwent efficient biocatalytic hydrolysis under very mild conditions to afford the corresponding (S)-α-alkylarylglycines and (R)-α-alkylarylglycine
- Wang, Mei-Xiang,Lin, Shuan-Jun,Liu, Jun,Zheng, Qi-Yu
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p. 439 - 445
(2007/10/03)
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- Fungicidal 2-imidazolin-5-ones and 2-imidazoline-5-thiones
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Fungicidal 2-imidazolin-5-ones and 2-imidazoline-5-thiones, processes for their preparation, fungicidal compositions containing them, and methods of using them to treat or prevent fungal disease in crops.
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- Applications of the sulfinimine-mediated asymmetric strecker synthesis to the synthesis of α-alkyl α-amino acids
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Addition of Et2AlCN and i-PrOH to ketosulfinimines (N-sulfinyl imines) affords corresponding α-alkyl α-amino nitriles in moderate to good yields. The diastereoselectivity is largely dependent on the E/Z isomer ratio of the ketosulfinimine. Hydrolysis of the diastereomerically pure amino nitriles affords enantiopure α-alkyl α-amino acids in moderate to good yields.
- Davis,Lee,Zhang,Fanelli
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p. 8704 - 8708
(2007/10/03)
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- Fungicidal 2-imidazolin-5-ones and 2-imidazoline-5-thiones
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Fungicidal 2-imidazolin-5-ones and 2-imidazoline-5-thiones, processes for their preparation, fungicidal compositions containing them and methods of using them to treat or prevent fungal disease in crops.
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- Fungicidal 2-imidazolin-5-ones and 2-imidazoline-5-thiones
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Fungicidal 2-imidazolin-5-ones and 2-imidazoline-5-thiones, processes for their preparation, fungicidal compositions containing them and methods of using them to treat or prevent fungal disease in crops.
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- Stereocontrolled synthesis of α,α-disubstituted α-aminoaldehydes and α-aminoacids using a [3,3] allylic trichloracetimidate rearrangement
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Sigmatropic rearrangement of trichloracetimidates derived from syn monoprotected allylic diols 3 resulting from the condensation of vinylalanes or cuprates with α-alkoxyaldehydes afforded diastereomerically pure allylic amines 6. The oxidative cleavage of these amines allowed the access to α,α-disubstituted α-aminoacids in high enantiomeric purity.
- Imogai, Hassan,Petit, Yves,Larcheveque, Marc
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p. 2573 - 2576
(2007/10/03)
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- L-phenylalanine cyclohexylamide: A simple and convenient auxiliary for the synthesis of optically pure α,α-disubstituted (R)- and (S)-amino acids
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This work describes L-phenylalanine cyclohexylamide (5c) as a simple, cheap, and powerful chiral auxiliary for the synthesis of a series of optically pure α,α-disubstituted (R)- and (S)-amino acids of type 1, such as (R)- and (S)-2-methyl-phenylalanine (1a), (R)- and (S)-2-methyl-2-phenylglycine (1b), and (R)- and (S)-2-methylvaline (1c). These amino acids were efficiently transformed into the suitably protected and activated amino-acid building blocks (R)- and (S)-12b and (R)- and (S)-12c which are ready for incorporation into peptides by solution or solid-phase techniques. Based on the crystal structures of 6b, 6c, and 7a belonging to the diastereoisomeric peptides series 6 and 7, the absolute configurations of each member of the series were determined. β-Turn geometries of type II' and I were observed for 6b and 7a, respectively, whereas 6c crystallized in an extended conformation. The impacts of side-chain variation on conformation and crystal packing of these triamides are discussed.
- Obrecht,Bohdal,Broger,Bur,Lehmann,Ruffieux,Schonholzer,Spiegler,Muller
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p. 563 - 580
(2007/10/02)
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- Synthesis of dipeptides containing α-substituted amino acids; their use as chiral ligands in Lewis-acid-catalyzed reactions
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L-α-Methylphenylalanine, obtained by enzymatic resolution of the corresponding racemic amide with amidase from Ochrobactrum anthropi NCIMB 40321, was used in the synthesis of dipeptides containing α-substituted amino acids.The 2-hydroxynaphthalene-1-carboxaldehyde Schiff bases of the dipeptides (1 and 2) were tested as Ti(IV) and Al(III) complexes in asymmetric Lewis-acid-catalyzed reactions.Only the Al(III) complex of 2 showed moderate enantioselectivity in the cyanation reaction of benzaldehyde with TMS-CN.
- Kaptein, Bernard,Monaco, Vania,Broxterman, Quirinus B.,Schoemaker, Hans E.,Kamphuis, Johan
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p. 231 - 238
(2007/10/02)
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- Enzymatic resolution of α,α-disubstituted α-amino acid esters and amides
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The scope and limitations of the enzymatic resolution of α,α-disubstituted α-amino acid amides by an amino acid amidase from Mycobacterium neoaurum and of the corresponding ethyl esters with Pig liver esterase (PLE) have been studied. Moderate enantiomeric excesses were obtained with PLE, with only a narrow substrate specificity. Mycobacterium neoaurum on the contrary yields a broad range of S-α,α-disubstituted α-amino acids 1 and the corresponding R-amides 2.
- Kaptein,Boesten,Broxterman,Peters,Schoemaker,Kamphuis
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p. 1113 - 1116
(2007/10/02)
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- REACTIONS OF FLUOROBENZENE TRICARBONYLCHROMIUM COMPLEXES WITH ANIONS FROM SCHIFF BASES OF α-AMINO ESTERS; ENANTIOSELECTIVE SYNTHESIS OF α-ARYL AMINO ACIDS
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We report here a convenient synthesis of α-substituted aryl amino acids via the addition of α-imino esters to fluorobenzene tricarbonylchromium complexes.Optically pure α-aryl amino acids have been prepared by enantioselective substitution of fluorobenzene complexes using Schiff bases of L-alanine, leucine and valine methyl esters and (1R,2R,5R)-2-hydroxypinan-3-one.
- Chaari, Mohamed,Jenhi, Aicha,Lavergne, Jean-Pierre,Viallefont, Philippe
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p. 4619 - 4630
(2007/10/02)
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- Synthese enantioselective d'α-aryl amino acides: subtitution nucleophile aromatique sur le fluorobenzene chrome tricarbonyle d'enolates chiraux
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We report here a convenient synthesis of optically pure α-aryl amino acids by enantioselective substitution of fluorobenzene tricarbonylchromium using the Schiff bases of L-alanine methyl ester with (1R,2R,5R)-2-hydroxy-3-pinanone in presence of LDA or deprotonated 2-(tert-butyl)-4-methyl-1,3-oxazolidin-5 one.
- Chaari, M.,Jenhi, A.,Lavergne, J.-P.,Viallefont, Ph.
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p. C10 - C13
(2007/10/02)
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- Synthesis of Optically Pure α-Alkylated α-Amino Acids and a Single-Step Method for Enatiomeric Excess Determination
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A method for the enzymatic resolution of the amides of some racemic α-alkylated amino acids is described as well as a method involving derivatization with (S)-2-chloropropionyl chloride followed by 1H NMR analysis to establish the enantiomeric excesses of the free amino acids.
- Kruizinga, Wim H.,Bolster, John,Kellogg, Richard M.,Kamphuis, Johan,Boesten, Wilhelmus H. J.,et al.
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p. 1826 - 1827
(2007/10/02)
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