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Enantioselective kinetic resolution of phenylalkyl carboxylic acids using metagenome-derived esterases.

Fernández-Álvaro E, Kourist R, Winter J, Böttcher D, Liebeton K, Naumer C, Eck J, Leggewie C, Jaeger KE, Streit W, Bornscheuer UT - Microb Biotechnol (2009)

Bottom Line: Out of these, 20 enzymes were found to be active and were subjected to analytical scale biocatalysis in order to determine their enantioselectivity.The most enantioselective and also enantiocomplementary biocatalysts were then used for preparative scale reactions.Thus, both enantiomers of each of the three phenylalkyl carboxylic acids studied could be obtained in excellent optical purity and high yields.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Biotechnology and Enzyme Catalysis, Institute of Biochemistry, Greifswald University, Felix-Hausdorff-Str. 4, D-17487 Greifswald, Germany.

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Racemic phenylalkyl carboxylic acids 1a–3a studied.
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f1: Racemic phenylalkyl carboxylic acids 1a–3a studied.

Mentions: Thus, enantiopure arylalkyl carboxylic acids are attractive synthetic targets and a variety of methodologies have been developed to obtain these compounds. Chemical syntheses (Sonawane et al., 1992) like the asymmetric hydrogenation of the unsaturated derivatives (Sun et al., 2007) or Friedel‐Crafts alkylation of aromatic precursors (Piccolo et al., 1991) proved to be effective. However, a biocatalytic synthetic route would not only offer an alternative access, but also represents an environmentally more benign method. The preparation of pure enantiomers of these carboxylic acids can be performed through kinetic resolution of their esters with enantioselective hydrolases (esterases or lipases), which are still the enzyme class most widely used in organic synthesis (Faber, 2004; Bornscheuer and Kazlauskas, 2006). So far, lipases selective towards one enantiomer of the phenylalkyl carboxylic acids 1a–3a (see Fig. 1) and their derivatives have been successfully applied in kinetic resolutions (Varadharaj et al., 1998; Kamal et al., 2007) and dynamic kinetic resolutions of their thioesters (Um and Drueckhammer, 1998). Very recently a remarkable non‐enzymatical approach was published using crystallization with abrasive grinding for complete deracemization of a naproxen ester (Noorduin et al., 2009).


Enantioselective kinetic resolution of phenylalkyl carboxylic acids using metagenome-derived esterases.

Fernández-Álvaro E, Kourist R, Winter J, Böttcher D, Liebeton K, Naumer C, Eck J, Leggewie C, Jaeger KE, Streit W, Bornscheuer UT - Microb Biotechnol (2009)

Racemic phenylalkyl carboxylic acids 1a–3a studied.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815947&req=5

f1: Racemic phenylalkyl carboxylic acids 1a–3a studied.
Mentions: Thus, enantiopure arylalkyl carboxylic acids are attractive synthetic targets and a variety of methodologies have been developed to obtain these compounds. Chemical syntheses (Sonawane et al., 1992) like the asymmetric hydrogenation of the unsaturated derivatives (Sun et al., 2007) or Friedel‐Crafts alkylation of aromatic precursors (Piccolo et al., 1991) proved to be effective. However, a biocatalytic synthetic route would not only offer an alternative access, but also represents an environmentally more benign method. The preparation of pure enantiomers of these carboxylic acids can be performed through kinetic resolution of their esters with enantioselective hydrolases (esterases or lipases), which are still the enzyme class most widely used in organic synthesis (Faber, 2004; Bornscheuer and Kazlauskas, 2006). So far, lipases selective towards one enantiomer of the phenylalkyl carboxylic acids 1a–3a (see Fig. 1) and their derivatives have been successfully applied in kinetic resolutions (Varadharaj et al., 1998; Kamal et al., 2007) and dynamic kinetic resolutions of their thioesters (Um and Drueckhammer, 1998). Very recently a remarkable non‐enzymatical approach was published using crystallization with abrasive grinding for complete deracemization of a naproxen ester (Noorduin et al., 2009).

Bottom Line: Out of these, 20 enzymes were found to be active and were subjected to analytical scale biocatalysis in order to determine their enantioselectivity.The most enantioselective and also enantiocomplementary biocatalysts were then used for preparative scale reactions.Thus, both enantiomers of each of the three phenylalkyl carboxylic acids studied could be obtained in excellent optical purity and high yields.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Biotechnology and Enzyme Catalysis, Institute of Biochemistry, Greifswald University, Felix-Hausdorff-Str. 4, D-17487 Greifswald, Germany.

Show MeSH