Addition of Amines to C = C Bonds

Wubbolts, Marcel

doi:10.1002/9783527618262.ch12f

Cited by 3 publications

(1 citation statement)

References 27 publications

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“…In industry, aspartase is used as biocatalyst for the preparation of enantiopure l -aspartic acid, an important starting compound for the synthesis of artificial sweeteners such as N -( l -α-aspartyl)- l -phenylalanine 1-methylester ( 10 , Scheme A), which is also known as aspartame. , Notably, N - and 3-substituted derivatives of l -aspartic acid are highly valuable as tools for biological research and as chiral building blocks for a range of pharmaceuticals. − However, the synthesis of these l -aspartic acid derivatives in enantiopure form remains a major challenge in synthetic chemistry. In principle, the stereo- and regioselective addition of amine nucleophiles to the double bonds of fumarate and its derivatives catalyzed by aspartases appears to be a very attractive strategy for the synthesis of these compounds (Scheme B).…”

Section: Aspartate Ammonia Lyase (Aspartase)mentioning

confidence: 99%

Catalytic Mechanisms and Biocatalytic Applications of Aspartate and Methylaspartate Ammonia Lyases

et al. 2012

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Ammonia lyases catalyze the formation of α,β-unsaturated bonds by the elimination of ammonia from their substrates. This conceptually straightforward reaction has been the emphasis of many studies, with the main focus on the catalytic mechanism of these enzymes and/or the use of these enzymes as catalysts for the synthesis of enantiomerically pure α-amino acids. In this Review aspartate ammonia lyase and 3-methylaspartate ammonia lyase, which represent two different enzyme superfamilies, are discussed in detail. In the past few years, the three-dimensional structures of these lyases in complex with their natural substrates have revealed the details of two elegant catalytic strategies. These strategies exploit similar deamination mechanisms that involve general-base catalyzed formation of an enzyme-stabilized enolate anion (aci-carboxylate) intermediate. Recent progress in the engineering and application of these enzymes to prepare enantiopure l-aspartic acid derivatives, which are highly valuable as tools for biological research and as chiral building blocks for pharmaceuticals and food additives, is also discussed.

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Section: Aspartate Ammonia Lyase (Aspartase)mentioning

confidence: 99%

Catalytic Mechanisms and Biocatalytic Applications of Aspartate and Methylaspartate Ammonia Lyases

et al. 2012

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Use of Enzymes in the Synthesis of Amino Acids

Sonke

Kaptein

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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Biocatalytic Enantioselective Synthesis of N‐Substituted Aspartic Acids by Aspartate Ammonia Lyase

Weiner

Poelarends

Janssen³

et al. 2008

Chemistry A European J

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The gene encoding aspartate ammonia lyase (aspB) from Bacillus sp. YM55‐1 has been cloned and overexpressed, and the recombinant enzyme containing a C‐terminal His6 tag has been purified to homogeneity and subjected to kinetic characterization. Kinetic studies have shown that the His6 tag does not affect AspB activity. The enzyme processes L‐aspartic acid, but not D‐aspartic acid, with a Km of ≈15 mM and a kcat of ≈40 s−1. By using this recombinant enzyme in the reverse reaction, a set of four N‐substituted aspartic acids were prepared by the Michael addition of hydroxylamine, hydrazine, methoxylamine, and methylamine to fumarate. Both hydroxylamine and hydrazine were found to be excellent substrates for AspB. The kcat values are comparable to those observed for the AspB‐catalyzed addition of ammonia to fumarate (≈90 s−1), whereas the Km values are only slightly higher. The products of the enzyme‐catalyzed addition of hydrazine, methoxylamine, and methylamine to fumarate were isolated and characterized by NMR spectroscopy and HPLC analysis, which revealed that AspB catalyzes all the additions with excellent enantioselectivity (>97 % ee). Its broad nucleophile specificity and high catalytic activity make AspB an attractive enzyme for the enantioselective synthesis of N‐substituted aspartic acids, which are interesting building blocks for peptide and pharmaceutical synthesis as well as for peptidomimetics.

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Addition of Amines to C = C Bonds

Cited by 3 publications

References 27 publications

Catalytic Mechanisms and Biocatalytic Applications of Aspartate and Methylaspartate Ammonia Lyases

Catalytic Mechanisms and Biocatalytic Applications of Aspartate and Methylaspartate Ammonia Lyases

Use of Enzymes in the Synthesis of Amino Acids

Biocatalytic Enantioselective Synthesis of N‐Substituted Aspartic Acids by Aspartate Ammonia Lyase

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