Preparative deracemization of unnatural amino acids

Abstract

Unnatural amino acids are a growing class of intermediates required for pharmaceuticals, agrochemicals and other industrial products. However, no single method has proven sufficiently versatile to prepare these compounds broadly at scale. To address this need, we have developed a general chemoenzymatic process to prepare enantiomerically pure l-and d-amino acids in high yield by deracemization of racemic starting materials. This method involves the concerted action of an enantioselective oxidase biocatalyst and a nonselective chemical reducing agent to effect the stereoinversion of one enantiomer and can result in an enantiomeric excess of >99% from the starting racemate, and product yields of over 90%. This approach compares very favourably with resolution processes, which have a maximum single-pass yield of 50%. We have developed efficient methods to adapt the process towards new target compounds and to optimize key factors that influence process efficiency and offer competitive economics at scale. C 2006 Biochemical Society 287

One-pot synthesis of (R)- and (S)-phenylglycinol from bio-based l-phenylalanine by an artificial biocatalytic cascade

“…Therefore, the bio-based l -α-amino acids can make a significant contribution to the economic and ecological production of chemical products and materials. In the past decades, several methods have been developed for converting l -α-amino acids into other high added-value compounds (Fotheringham et al 2006 ; Studte et al 2008 ; Zhang et al 2019c ). For example, cascade biocatalysis processes have been used for conversion of l -phenylalanine into chiral styrene oxides, 1-phenylethane-1,2-diols, mandelic acids and phenylglycines (Zhou et al 2016 ).…”

Development of a Combination Fermentation Strategy to Simultaneously Increase Biomass and Enzyme Activity of D-amino acid Oxidase Expressed in Escherichia Coli

“…Because of its strict stereoselectivity, DAAO has been used to produce unnatural l-amino acids [6,7]. lamino acids are important intermediate compounds in the synthesis of pharmaceuticals [8,9].…”

The stabilizing effects of immobilization in D-amino acid oxidase from Trigonopsis variabilis

“…While DAOs show absolute selectivity for conversion of R -configured α-amino acids, these enzymes tolerate a wide range of structural variations in the side chain of their substrates. Based on these properties, several technological applications have been suggested for DAOs, including the conversion of amino acid precursors to α-keto acids [ 5 ], the resolution of racemic mixtures of (non-natural) amino acids [ 6 , 7 ], and the use in biosensors for quantitative detection of D-amino acids [ 8 - 10 ]. The currently most important application, however, is in the two-step enzymatic conversion of cephalosporin C to 7-amino cephalosporanic acid (7-ACA), a key intermediate for numerous cephem antibiotics [ 11 , 12 ].…”