- An efficient and selective enzymatic oxidation system for the synthesis of enantiomerically pure D-tert-Leucine
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(Matrix presented) D-tert-Leucine was prepared with an enantiomeric excess of >99% by an enzyme-catalyzed oxidative resolution of the racemic mixture of DL-tert-leucine with use of leucine dehydrogenase. The L-amino acid was oxidized completely due to coupling of the primary reaction with a highly efficient irreversible NAD+-regenerating step by NADH oxidase.
- Hummel, Werner,Kuzu, Mutlu,Geueke, Birgit
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Read Online
- Simultaneous Preparation of (S)-2-Aminobutane and d -Alanine or d -Homoalanine via Biocatalytic Transamination at High Substrate Concentration
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(S)-2-Aminobutane, d-alanine, and d-homoalanine are important intermediates for the production of various active pharmaceutical ingredients and food additives. The preparation of these small chiral amine or amino acids with high water solubility still demands searching for efficient methods. In this work, we identified an ω-transaminase (ω-TA) from Sinirhodobacter hungdaonensis (ShdTA) that catalyzed the kinetic resolution of racemic 2-aminobutane at a concentration of 800 mM using pyruvate as the amino acceptor, leading to the simultaneous isolation of enantiopure (S)-2-aminobutane and d-alanine in 46% and 90% yield, respectively. In addition, (S)-2-aminobutane (98% ee) and d-homoalanine (99% ee) were isolated in 45% and 93% yield, respectively, in the kinetic resolution of racemic 2-aminobutane at a concentration of 400 mM coupled with deamination of l-threonine by threonine deaminase. We thus developed a biocatalytic process for the practical synthesis of these valuable small chiral amine and d-amino acids.
- Li, Jianjiong,Wang, Yingang,Wu, Qiaqing,Yao, Peiyuan,Yu, Shanshan,Zhu, Dunming
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supporting information
(2022/03/01)
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- Method for preparing D-type or L-type tert-leucine
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The invention discloses a method for preparing D-type or L-type tert-leucine, and belongs to the technical field of organic synthesis. The method comprises the following steps: 1, condensing glyoxylate serving as a raw material with chiral tert-butyl sulfinamide to obtain Schiff base; and 2, carrying out a reaction on the Schiff base with a tert-butyl Grignard reagent and a catalyst under a low-temperature condition, and hydrolyzing the reaction product under an acid/alkali condition to obtain D-type or L-type tert-leucine. The method is simple and convenient to operate and high in reaction yield, the purity and content of the obtained product are greater than 99%, the content of a single impurity is less than 0.2%, the chiral purity is greater than or equal to 98.5%, and the method has apotential process amplification prospect.
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Paragraph 0036; 0046-0048
(2020/06/16)
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- Structure-guided engineering of: Meso -diaminopimelate dehydrogenase for enantioselective reductive amination of sterically bulky 2-keto acids
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meso-Diaminopimelate dehydrogenase (DAPDH) and mutant enzymes are an excellent choice of biocatalysts for the conversion of 2-keto acids to the corresponding d-amino acids. However, their application in the enantioselective reductive amination of bulky 2-keto acids, such as phenylglyoxylic acid, 2-oxo-4-phenylbutyric acid, and indole-3-pyruvic acid, is still challenging. In this study, the structure-guided site-saturation mutagenesis of a Symbiobacterium thermophilum DAPDH (StDAPDH) gave rise to a double-site mutant W121L/H227I, which showed dramatically improved enzyme activities towards various 2-keto acids including these sterically bulky substrates. Several d-amino acids were prepared in optically pure form. The molecular docking of substrates into the active sites of wild-type and mutant W121L/H227I enzymes revealed that the substrate binding cavity of the mutant enzyme was reshaped to accommodate these bulky substrates, thus leading to higher enzyme activity. These results lay a foundation for further shaping the substrate binding pocket and manipulating the interactions between the substrate and binding sites to access highly active d-amino acid dehydrogenases for the preparation of synthetically challenging d-amino acids.
- Cheng, Xinkuan,Chen, Xi,Feng, Jinhui,Wu, Qiaqing,Zhu, Dunming
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p. 4994 - 5002
(2018/10/17)
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- Sequential ruthenium catalysis for olefin isomerization and oxidation: Application to the synthesis of unusual amino acids
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How can you use a ruthenium isomerization catalyst twice? A ruthenium-catalyzed sequence for the formal two-carbon scission of allyl groups to carboxylic acids has been developed. The reaction includes an initial isomerization step using commercially available ruthenium catalysts followed by in situ transformation of the complex to a metal-oxo species, which is capable of catalyzing subsequent oxidation reactions. The method enables enantioselective syntheses of challenging α-tri- and tetrasubstituted α-amino acids including an expedient total synthesis of the antiepileptic drug levetiracetam.
- Liniger, Marc,Liu, Yiyang,Stoltz, Brian M.
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supporting information
p. 13944 - 13949
(2017/11/06)
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- Preparation D at the same time-and L- uncle leucine method (by machine translation)
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This invention relates to a kind of simultaneously preparing D-and L- uncle leucine method, comprising the following steps: step (1): the positive butanol and 1,1-dichloroethylene reaction, to obtain 3,3-dimethyl butanoic acid product; step (2): in the 3,3-dimethyl-butyric acid, a catalyst is added in the product, at the same time access air and chlorine, to chloropivaloyl, to obtain 2-chloro -3,3-dimethyl butanoic acid; step (3): the obtained 2-chloro -3,3-dimethyl butanoic acid for aminolysis reaction, to obtain D-, L-tert-leucine; step (4): the D-, L-tert-leucine for acetylation and acetyl chloride, with L-heat-stable to amino acid acylase split and other processing, respectively obtained L-tert-leucine and D-tert-leucine; step (5): the split recovery acetylation or chloroactic acidylated recovery D-tert-leucine for racemic, is circulated and split. The present invention uses low-cost normal butanol and 1,1-dichloroethylene as the starting material. From economic benefits speaking, the cost of this invention is substantially below that of the biological reduction method. (by machine translation)
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- A process for the preparation of enantiomerically pure tert-leucine
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A Process for the Preparation of Enantiomerically Pure tert-Leucine : Enantiomerically pure L-tert-leucine and D-tert-leucine were prepared from (DL)-tert-leucine by diastereomeric salt formation using dibenzoyl-d-tartaric acid as the resolving agent.
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Page/Page column 4
(2012/10/18)
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- PROCESS FOR THE PREPARATION OF ENANTIOMERICALLY PURE tert-LEUCINE
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Enantiomerically pure L-tert-leucine and D-tert-leucine were prepared from (DL)-tert-leucine by diastereomeric salt formation using dibenzoyl-d-tartaric acid as the resolving agent.
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Page/Page column 2-3
(2012/10/08)
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- Enantioselective hydrocyanation of N-protected aldimines
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Enantioselective hydrocyanation of N-benzyloxycarbonyl aldimines catalyzed by a Ru[(S)-phgly]2[(S)-binap]/C6H5OLi system or a bimetallic complex [Li{Ru[(S)-phgly]2[(S)-binap]}]Cl affords the amino nitriles in 92 - 99% ee. The reaction is carried out in tert-C 4H9OCH3 with a substrate-to-catalyst molar ratio in the range of 500 - 5000 at -20 to 0°C. Primary, secondary, and tertiary alkyl imines as well as the aryl and heteroaryl substrates are smoothly cyanated to produce the desired products in high yield.
- Uemura, Masato,Kurono, Nobuhito,Ohkuma, Takeshi
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supporting information; experimental part
p. 882 - 885
(2012/04/05)
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- Enzymatic approach to both enantiomers of N-Boc hydrophobic amino acids
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Protease catalysed hydrolysis of N-Boc-amino acid esters allows us to obtain N-Boc l-acids and d-esters of amino butanoic acid, nor-leucine, nor-valine, leucine and t-leucine in excellent ee. The reaction occurs in short reaction times and high concentrations. When a biphasic system (buffer-MTBE) is employed, a strong solvent effect is observed. This method could be of significance for the preparation of d-t-leucine, for which a practical method is currently unavailable.
- Agosta, Eleonora,Caligiuri, Antonio,D'Arrigo, Paola,Servi, Stefano,Tessaro, Davide,Canevotti, Renato
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p. 1995 - 1999
(2007/10/03)
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- PROCESS FOR PRODUCING TERT-LEUCINE
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The present invention provides a method of producing tert-leucine, which includes reacting tert-leucine with substituted benzenesulfonic acid represented by the following formula (1) wherein R1 and R2 are each independently a hydrogen atom, an alkyl group or a halogen atom, except a compound wherein R1 and R2 are both hydrogen atoms, in a solvent, to give tert-leucine·substituted benzenesulfonate represented by the following formula (2) wherein R1 and R2 are the same substituents as above, separating the salt by crystallization and then dissociating the salt. According to the present invention, a production method of tert-leucine is provided, which includes forming a tert-leucine salt hardly soluble in a solvent and crystallization thereof to efficiently recover tert-leucine from the solvent.
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Page/Page column 8
(2008/06/13)
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- Method for the preparation of enantiomerically enriched compounds
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Process for the preparation of a diasteromerically enriched phenylglycine amide derivative in which an enantomerically enriched phenylglycine amide is converted into the corresponding Schiff base with the aid of compound R2—C(O)—R3, and the Schiff base obtained is subsequently converted into the diastereomerically enriched phenyglycine amide derivative with the aid of a cyanide source, a reducing agent or an allyl organometallic compound. The phenylglycine amide derivatives obtained are interesting starting materials for the preparation of for example enantimerically enriched α- and or β-amino acids and derivatives thereof, such as amides and esters, and amines.
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- Screening for Amidases: Isolation and Characterization of a Novel D-Amidase from Variovorax paradoxus
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Using racemic tert-leucine amide as sole nitrogen source in minimal medium, 162 strains were isolated by enrichment techniques and shown to contain amidase activity. Among these isolates three D-amidase producers were found and identified as Variovorax pa
- Krieg, Lutz,Ansorge-Schumacher, Marion B.,Kula, Maria-Regina
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p. 965 - 973
(2007/10/03)
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- Enzyme-assisted Preparation of D-tert.-Leucine
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Optically pure D-tert.-leucine was obtained by the enzymatic hydrolysis of (±)-N-acetyl-tert. leucine chloroethyl ester after about 50% conversion, this being catalyzed by a protease from Bacillus licheniformis (Alcalase), and subsequent acidic saponification of the recovered ester. Among the methyl, ethyl, octyl, chloroethyl and trichloroethyl esters, the chloroethyl ester exhibited the highest rate of hydrolysis.
- Laumen, Kurt,Ghisalba, Oreste,Auer, Kurt
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p. 1977 - 1980
(2007/10/03)
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- Enantioselective synthesis of α-amino acids and monosubstituted 1,2- diamines by conjugate addition of 4-phenyl-2-oxazolidinone to nitroalkenes
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The addition of the potassium salt of (R)- or (S)-4-phenyl-2- oxazolidinone to monosubstituted nitroalkenes proceeded with very good diastereoselectivity. Several of the addition products were converted into α-amino acids and monosubstituted 1,2-diamines of high enantiomeric purity.
- Lucet, Denis,Sabelle, Stephane,Kostelitz, Olivier,Le Gall, Thierry,Mioskowski, Charles
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p. 2583 - 2591
(2007/10/03)
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- Enantioselective synthesis of α-amino acids from nitroalkenes
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The products of the conjugate addition of (R)-4-phenyl-2-oxazolidinone on monosubstituted nitroalkenes, were converted into D-α-amino acids of high enantiomeric purity.
- Sabelle, Stephane,Lucet, Denis,Le Gall, Thierry,Mioskowski, Charles
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p. 2111 - 2114
(2007/10/03)
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- CARBOHYDRATES AS CHIRAL TEMPLATES: ASYMMETRIC UGI-SYNTHESIS OF ALPHA-AMINO ACIDS USING GALACTOSYLAMINES AS THE CHIRAL MATRICES
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In the presence of Lewis acid catalysts O-acetyl- (1) and O-pivaloyl- (2) protected β-D-galactopyranosylamines react with aldehydes, isocyanides and carboxylic acids in Ugi-four-component-condensations to give the corresponding N-galactosyl-amino acid amide derivatives 3, 5 in almost quantitative yields.Zinc chloride is the most effective Lewis acid catalyst.At 0 deg C or even at room temperature the (2R,β-D)-diastereomers of the amino acid derivatives 3, 5 are formed with high diastereoselectivity.If the sterically more demanding O-pivaloyl galactosylamine 2 is used at -78 deg C to -25 deg C the stereoselectivity often exeeds 20:1 favouring the (2R,β-D) diastereomers 5.After one recrystallisation pure (R)-amino acid derivatives 5 are obtained in yields of 80-95percent.In addition to the high yields and stereoselectivity the amino acid synthesis described here has the further advantage that it neither requires organometallic reagents and intermediates nor exclusion of oxygen and moisture.Two step acid hydrolysis of the N-galactosylamino acid amide derivatives 5 delivers the enantiomerically pure (R)-amino-acids 8 in high yields.
- Kunz, Horst,Pfrengle, Waldemar
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p. 5487 - 5494
(2007/10/02)
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- SIMPLE OPTICAL RESOLUTION OF TERLEUCINE
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Underivatized terleucine (1) can be conveniently resolved into its L- and D-enantiomers by recrystallization of its diastereoisomeric 10-camphorsulphonate salts.
- Viret, Joelle,Patzelt, Heiko,Collet, Andre
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p. 5865 - 5868
(2007/10/02)
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