Synthesis of Canonical and Noncanonical Amino Acids

The s)mthesis of all kinds of amino acids has been studied extensively in the last decades. Due to enhanced enzymatic and pharmacodynamic stability, as well as their diverse structures and biochemical properties, amino acids were maintained as chiral building blocks in numerous peptidomimetics, in single-enantiomer drugs, and also in various fields of agriculture [79,80]. Due to the wide substrate specificity of transaminases, these enzymes are suitable as biocatalysts for the amination of keto acids or deracemization of racemic amines to produce enantiopure amino acids [2,54,81]. 

Some nonproteinogenic amino acids, produced enzymatically, are shown in Table 29.4 for example, L-homophenylalanine, a key intermediate of levetiracetam and brivaracetam applicable as antiepileptic drugs, or D-fluoroalanine, a key intermediate of antibiotics inactivating the bacterial D-alanine transaminase. In Table 29.4 a selection of proteinogenic and nonproteinogenic amino acids, the used biocatalysts, synthesis strategies, and the substrates used are listed. 

The asymmetric synthesis via a-transaminases was described for L-phenylalanine and L-homophenylalanine in several reports and reviews [17,62,86]. Herein the focus is on ffl-transaminases that catalyzed the asymmetric synthesis of optically pure nonproteinogenic amino acids as building blocks for peptidomimetic and other pharmaceutical compounds. The overall advantage of -transaminase-catalyzed reactions is the ability to use achiral amino donors like benzylamine, which thermodynamically favors the equilibriinn toward the product side. 

For the synthesis of L-2-aminobutyric acid, the -transaminase from Vibrio flu-vialis with 2-oxobutyric acid and benzylamine as substrates was established [46]. 

TABLE 29.4 An Overview of Some Industrial and Pharmacologically Relevant Amino Acids 

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