- Enzymatic synthesis of chiral phenylalanine derivatives by a dynamic kinetic resolution of corresponding amide and nitrile substrates with a multi-enzyme system
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Mutant α-amino-ε-caprolactam (ACL) racemase (L19V/L78T) from Achromobacter obae with improved substrate specificity toward phenylalaninamide was obtained by directed evolution. The mutant ACL racemase and thermostable mutant D-amino acid amidase (DaaA) from Ochrobactrum anthropi SV3 co-expressed in Escherichia coli (pACLmut/pDBFB40) were utilized for synthesis of (R)-phenylalanine and non-natural (R)-phenylalanine derivatives (4-OH, 4-F, 3-F, and 2-F-Phe) by dynamic kinetic resolution (DKR). Recombinant E. coli with DaaA and mutant ACL racemase genes catalyzed the synthesis of (R)-phenylalanine with 84% yield and 99% ee from (RS)-phenylalaninamide (400 mM) in 22 h. (R)-Tyrosine and 4-fluoro-(R)-phenylalanine were also efficiently synthesized from the corresponding amide compounds. We also co-expresed two genes encoding mutant ACL racemase and L-amino acid amidase from Brevundimonas diminuta in E. coli and performed the efficient production of various (S)-phenylalanine derivatives. Moreover, 2-aminophenylpropionitrile was converted to (R)-phenylalanine by DKR using a combination of the non-stereoselective nitrile hydratase from recombinamt E. coli and mutant ACL racemase and DaaA from E. coli encoding mutant ACL racemase and DaaA genes. Copyright
- Yasukawa, Kazuyuki,Asano, Yasuhisa
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p. 3327 - 3332
(2013/01/15)
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- Practical and convenient enzymatic synthesis of enantiopure α-amino acids and amides
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Catalyzed by the nitrile hydratase and the amidease in Rhodococcus sp. AJ270 cells under very mild conditions, a number of α-aryl- and α-alkyl-substituted DL-glycine nitriles 1 rapidly underwent a highly enantioselective hydrolysis to afford D-(-)-α-amino acid amides 2 and L-(+)-α-amino acids 3 in high yields with excellent enantiomeric excesses in most cases. The overall enantioselectivity of the biotransformations of nitriles originated from the combined effects of a high L-enantioselective amidase and a low enantioselective nitrile hydratase. The influence of the substrates on both reaction efficiency and enantioselectivity was also discussed in terms of steric and electronic effects. Coupled with chemical hydrolysis of D-(-)-α-phenylglycine amide, biotransformation of DL-phenylglycine nitrile was applied in practical scale to produce both D- and L-phenylglycines in high optical purity.
- Wang, Mei-Xiang,Lin, Shuang-Jun
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p. 6542 - 6545
(2007/10/03)
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- Highly efficient and enantioselective synthesis of L-arylglycines and D-arylglycine amides from biotransformations of nitriles
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Under very mild conditions, the Rhodococcus sp. AJ270-catalysed biotransformation of arylglycine nitriles 1, prepared easily from the reaction of substituted benzaldehydes, ammonium chloride and potassium cyanide, proceeded efficiently to produce optically active D-arylglycine amides 2 and L-arylglycines 3 in excellent yields with enantiomeric excesses higher than 99%.
- Wang, Mei-Xiang,Lin, Shuang-Jun
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p. 6925 - 6927
(2007/10/03)
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- Efficient chemoenzymatic synthesis of enantiomerically pure α-amino acids
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A general two-step chemoenzymatic synthesis for enantiomerically pure natural and nonnatural α-amino acids is presented. In the first step of the sequence, the ubiquitous educts aldehyde, amide and carbon monoxide react by palladium-catalyzed amidocarbonylation to afford the racemic N-acyl amino acids in excellent yields. In the second step, enzymatic enantioselective hydrolysis yields the free optically pure a-amino acid and the other enantiomer as the N-acyl derivative, both in optical purities of 85-99.5% ee. The advantage of the chemoenzymatic process compared to other amino acid synthesis are demonstrated by the preparation of various functionalized (-OR, -Cl, -F, -SR) α-amino acids on a 10-g scale.
- Beller, Matthias,Eckert, Markus,Geissler, Holger,Napierski, Bernd,Rebenstock, Heinz-Peter,Holla, E. Wolfgang
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p. 935 - 941
(2007/10/03)
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- Synthesis of Optically Active Arylglycines by Photolysis of Optically Active (β-Hydroxyamino) Carbene-Chromium(0) Complexes
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Photolysis of chromium complexes having the optically active amino alcohol (1R,2S)-(-)- or (1S,2R)-(+)-2-amino-1,2-diphenylethanol as the amino group produced aryl-substituted oxazinones in good yield with reasonable diastereoselectivity.Facile separation of diastereoisomers followed by mild reductive cleavage produced several arylglycines, having either electron-donating or withdrawing groups on the aromatic ring, in good overall yield and with excellent enantiomeric excess.
- Vernier, Jean-Michel,Hegedus, Louis S.,Miller, David B.
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p. 6914 - 6920
(2007/10/02)
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- Stereoselective synthesis of L-amino acids via Strecker and Ugi reactions on carbohydrate templates
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L-Amino acid derivatives are stereoselectively synthesized in high yield using 2,3,4-tri-O-pivaloyl-α-D-arabinopyranosylamine or 2,3,4-tri-O-pivaloyl-β-L-fucopyranosylamine as the chiral auxiliary in Strecker and Ugi reactions.
- Kunz,Pfrengle,Ruck,Sager
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p. 1039 - 1042
(2007/10/02)
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- CARBOHYDRATES AS CHIRAL TEMPLATES: DIASTEREOSELECTIVE UGI SYNTHESIS OF (S)-AMINO ACIDS USING O-ACYLATED D-ARABINOPYRANOSYLAMINE AS THE AUXILIARY
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Enantiomerically pure (S)-amino acids are synthesized via a highly diastereoselective Ugi reaction using 2,3,4-tri-O-pivaloyl-α-D-arabinopyranosylamine as the chiral template.
- Kunz, Horst,Pfrengle, Waldemar,Sager, Wilfried
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p. 4109 - 4110
(2007/10/02)
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- ASYMMETRIC INDUCTIVE SYNTHESIS OF α-AMINOARYLACETIC ACIDS IN CHIRAL MICELLAR SYSTEM
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In the micellar solution of chiral surfactant N-hexadecyl-N-methylephedrine bromide, seven α-aminoarylacetic acids were synthesized from corresponding aldehydes, the e.e.percent being about 28percent.
- Zhang, Yongmin,Li, Weixing
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p. 1685 - 1690
(2007/10/02)
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