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Development of novel biocatalytic routes toward the synthesis of Naproxen
[Thesis]. Manchester, UK: The University of Manchester; 2016.
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Abstract
Whilst pressure grows for ‘greener’ solutions to chemical synthesis, biocatalysis offers a cleaner and more efficient way of chemical production using ambient experimental conditions such as temperature and pressure. Biocatalysts can offer a route to enantioselective reactions that can produce pure yields of product. Reductases are capable of carrying out asymmetric reduction of C=C bonds which lead to important chiral compounds from alkenes. Old yellow enzymes were employed in the synthesis of the profen Naproxen by precursors with three different functional groups; nitro, carboxylic acid and methyl ester. Three routes were developed using the three precursors with activity detected with at several OYEs. Reactions towards Naproxen were completed by enzymatic or chemoenzymatic routes. Of particular interest was the direct reduction of 2-(6-methoxynaphthalen-2-yl)acrylate to (R)-Naproxen by OYEs, XenA and GYE. This reaction was run at a 50 mg scale with 85% yield of Naproxen observed. This activity of XenA and GYE towards substrates containing monoacid activating groups is as yet unreported in OYEs and leads the way to expand the biocatalytic potential of this enzyme group. Additional screens were carried out with XenA and GYE with 2-phenylacrylic acid and additional related substrates screened in an attempt to expand the substrate range of the OYEs. However, the only activity detected was that with XenA and 2-phenylacrylic acid, suggesting that XenA and GYE are not active with a wide range of monoacid containing substrates.