Journal ArticleDOI
Enzymatic Synthesis of Enantiopure α‐ and β‐Amino Acids by Phenylalanine Aminomutase‐Catalysed Amination of Cinnamic Acid Derivatives
Bian Wu,Wiktor Szymanski,Pieter Wietzes,Stefaan Marie André De Wildeman,Gerrit J. Poelarends,Ben L. Feringa,Dick B. Janssen +6 more
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TLDR
A novel synthetic strategy is described that is based on the finding that ring‐substituted (E)‐cinnamic acids can serve as a substrate in PAM‐catalysed ammonia addition reactions for the biocatalytic production of several important β‐amino acids.Abstract:
The phenylalanine aminomutase (PAM) from Taxus chinensis catalyses the conversion of alpha-phenylalanine to beta-phenylalanine, an important step in the biosynthesis of the N-benzoyl phenylisoserinoyl side-chain of the anticancer drug taxol. Mechanistic studies on PAM have suggested that (E)-cinnamic acid is an intermediate in the mutase reaction and that it can be released from the enzyme's active site. Here we describe a novel synthetic strategy that is based on the finding that ring-substituted (E)-cinnamic acids can serve as a substrate in PAM-catalysed ammonia addition reactions for the biocatalytic production of several important beta-amino acids. The enzyme has a broad substrate range and a high enantioselectivity with cinnamic acid derivatives; this allows the synthesis of several non-natural aromatic alpha- and beta-amino acids in excellent enantiomeric excess (ee > 99%). The internal 5-methylene-3,5-dihydroimidazol-4-one (1010) cofactor is essential for the PAM-catalysed amination reactions. The regioselectivity of amination reactions was influenced by the nature of the ring substituent.read more
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Recent advances in the catalytic asymmetric synthesis of β-amino acids
TL;DR: The progress in catalytic asymmetric synthesis of beta-amino acids is discussed, covering the literature since 2002 and the most important synthetic methods, such as hydrogenation, the Mannich reaction and conjugate additions are covered.
Journal ArticleDOI
New Generation of Biocatalysts for Organic Synthesis
TL;DR: The advantages and applications of the most recent and attractive biocatalysts--reductases, transaminases, ammonia lyases, epoxide hydrolases, and dehalogenases--will be discussed herein and exemplified by the syntheses of interesting compounds.
Journal ArticleDOI
Enzymatic asymmetric synthesis of chiral amino acids.
TL;DR: This review provides an overview of the reported methods for enzymatic asymmetric synthesis of chiral amino acids, including asymmetric reductive amination of keto acids, asymmetric transfer of an amino group to keto fatty acids, enantioselective addition of ammonia to α,β-unsaturated acids, and aldol condensation ofan amino acid to aldehydes.
Journal ArticleDOI
Recent progress in industrial biocatalysis.
TL;DR: This review focuses on selected examples integrating biocatalysts into a variety of industrially interesting processes ranging from the manufacture of smaller, chiral speciality chemicals to the synthesis of more complex pharmaceutical intermediates.
Journal ArticleDOI
High-Yield Biocatalytic Amination Reactions in Organic Synthesis
John M. Ward,Roland Wohlgemuth +1 more
TL;DR: The biocatalytic processes that have been developed show different strategies of overcoming the kinetic limitations of the transaminase reactions and show how some enzymes have been used in processes to make large quantities of chiral compounds with amino functionalities.
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Journal ArticleDOI
β-Peptides: Synthesis by Arndt-Eistert homologation with concomitant peptide coupling. Structure determination by NMR and CD spectroscopy and by X-ray crystallography. Helical secondary structure of a β-hexapeptide in solution and its stability towards pepsin
Dieter Seebach,Mark Overhand,Florian N. M. Kühnle,Bruno Martinoni,Lukas Oberer,Ulrich Hommel,Hans Widmer +6 more
TL;DR: The β-hexapeptide (H-β-HVal-β -HAla-Leu)2-2-OH (2) was obtained from the component Lβ-amino acids by conventional peptide synthesis, including fragment coupling as discussed by the authors.
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Recent advances in the stereoselective synthesis of β-amino acids
Mei Liu,Mukund P. Sibi +1 more
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A modern view of phenylalanine ammonia lyase
TL;DR: Key details relating to the physiological role of PAL, the mechanism of catalysis, methods of determination and purification, enzyme kinetics, and enzyme activity in nonaqueous media are discussed.
Journal ArticleDOI
Beta2-amino acids-syntheses, occurrence in natural products, and components of beta-peptides1,2.
Gérald Lelais,Dieter Seebach +1 more
TL;DR: This review gives an overview of the occurrence and importance of beta2-amino acids in nature, placing emphasis on the metabolic pathways of beta-aminoisobutyric acid (beta-Aib) and the appearance of beta1-aminos acids as secondary metabolites or as components of more complex natural products, such as peptides, depsipeptides, lactones, and alkaloids.
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Structural Basis for the Entrance into the Phenylpropanoid Metabolism Catalyzed by Phenylalanine Ammonia-Lyase
Holger Ritter,Georg E. Schulz +1 more
TL;DR: The enzyme from parsley was crystallized, and the structure was elucidated at 1.7-Å resolution, and a pathway of the catalyzed reaction is proposed in agreement with established biochemical data.