Biocatalytic retrosynthesis approaches to<scp>d</scp>-(2,4,5-trifluorophenyl)alanine, key precursor of the antidiabetic sitagliptin

Parmeggiani, Fabio; Casamajo, Arnau Rué; Colombo, Danilo; Ghezzi, Maria Chiara; Galman, James L.; Chica, Roberto A.; Brenna, Elisabetta; Turner, Nicholas J.

doi:10.1039/c9gc01902b

Cited by 21 publications

(20 citation statements)

References 45 publications

(23 reference statements)

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“…335,336 While mimicking the retrosynthetic approach developed by Corey, 337,338 the focus remains on key enzymatic steps to inspire retrobiocatalytic strategies. 339,340 Biocatalysis offers many ways to access key functional group interconversions and computational tools are now available [341][342][343] to help identify disconnections -a key strategy in retrosynthesis -and suitable starting materials with corresponding enzymes toward a target molecule.…”

Section: Conversion Of Prochiral Compounds Into Axially Chiral Compoundsmentioning

confidence: 99%

Enzymatic strategies for asymmetric synthesis

Hall

2021

RSC Chem. Biol.

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Section: Conversion Of Prochiral Compounds Into Axially Chiral Compoundsmentioning

confidence: 99%

Enzymatic strategies for asymmetric synthesis

Hall

2021

RSC Chem. Biol.

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“…The catalytic route involving PAL and LAAD has also been employed by Parmeggiani et al, who proposed four routes combining chemical catalysts and enzymes to produce D-(2,4,5-trifluorophenyl) alanine, a key precursor of the antidiabetic sitagliptin (Fig. 3) [41]. For example, of the proposed reaction routes, the intermediate keto acid was obtained by standard Erlenmeyer-Plöchl synthesis involving the chemical reagents N-acetylglycine, acetic anhydride, and anhydrous sodium acetate and then transformed into the product through reductive amination catalyzed by DAADH with GDH or DAAT with D-aspartate oxidase.…”

Section: Chemo-enzymatic Cascades Involving Ammonia Lyasementioning

confidence: 99%

Enzymatic cascade systems for D-amino acid synthesis: progress and perspectives

Fan

et al. 2021

Syst Microbiol and Biomanuf

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D-amino acids, different from the ubiquitous L-amino acids, are recognized as the "unnatural" amino acids. The applications of D-amino acids have drawn increasing interest from researchers in recent years, and D-amino acids are widely used in various industries, including for food products, pharmaceuticals, and agricultural chemicals. Inspired by the prevalent applications, many synthetic methods for D-amino acids have been developed, which are mainly divided into chemical synthetic methods and biosynthetic methods. Chemical synthesis of D-amino acids has a variety of disadvantages such as multiple reaction steps, low yields, low reaction rates, and difficulties in product extraction. Thus, biosynthetic methods utilizing enzymes are attracting increasing attention because they are more energy-saving and environmentally friendly compared to traditional chemical synthesis. Among all enzymatic methods, multi-enzymatic cascade catalytic methods have significant advantages, such as lower costs, no need for intermediate separation, and higher catalytic efficiency, which is ascribed to the spatial proximity of biocatalysts. In this review, advances in multi-enzyme cascade catalytic systems as well as chemoenzymatic approaches to synthesize D-amino acids are discussed.

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“…( Rg PAL) 6 – 8 , Petroselinum crispum ( Pc PAL) 9 – 11 and Anabaena variabilis ( Av PAL) 12 – 14 were shown to display activity on a broad range of substrates. Accordingly, PALs emerged as efficient biocatalysts for the production of d - and l -phenylalanine analogues 2 , 3 , 15 , PAL-based industrial processes such as the multi-ton scale production of ( S )-2,3-dihydro-1 H -indole-2-carboxylic acid by DSM (Netherlands) being also established 16 . Recent protein engineering of PALs, but also of TALs and PAMs increased their catalytic activity 17 – 20 , selectivity 21 , 22 and/or extended their substrate scope 23 – 25 .…”

Section: Introductionmentioning

confidence: 99%

Fluorescent enzyme-coupled activity assay for phenylalanine ammonia-lyases

Moisă

Amariei

Nagy

et al. 2020

Sci Rep

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Phenylalanine ammonia-lyases (PALs) catalyse the non-oxidative deamination of l-phenylalanine to trans-cinnamic acid, while in the presence of high ammonia concentration the reverse reaction occurs. PALs have been intensively studied, however, their industrial applications for amino acids synthesis remained limited, mainly due to their decreased operational stability or limited substrate specificity. The application of extensive directed evolution procedures to improve their stability, activity or selectivity, is hindered by the lack of reliable activity assays allowing facile screening of PAL-activity within large-sized mutant libraries. Herein, we describe the development of an enzyme-coupled fluorescent assay applicable for PAL-activity screens at whole cell level, involving decarboxylation of trans-cinnamic acid (the product of the PAL reaction) by ferulic acid decarboxylase (FDC1) and a photochemical reaction of the produced styrene with a diaryltetrazole, that generates a detectable, fluorescent pyrazoline product. The general applicability of the fluorescent assay for PALs of different origin, as well as its versatility for the detection of tyrosine ammonia-lyase (TAL) activity have been also demonstrated. Accordingly, the developed procedure provides a facile tool for the efficient activity screens of large mutant libraries of PALs in presence of non-natural substrates of interest, being essential for the substrate-specificity modifications/tailoring of PALs through directed evolution-based protein engineering.

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Biocatalytic retrosynthesis approaches tod-(2,4,5-trifluorophenyl)alanine, key precursor of the antidiabetic sitagliptin

Abstract: Six chemo-enzymatic routes for the synthesis of a trifluorinated d-phenylalanine have been described and compared, including the first example of a fully biocatalytic d-hydroamination.

Cited by 21 publications

References 45 publications

Enzymatic strategies for asymmetric synthesis

Enzymatic strategies for asymmetric synthesis

Enzymatic cascade systems for D-amino acid synthesis: progress and perspectives

Fluorescent enzyme-coupled activity assay for phenylalanine ammonia-lyases

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