No description available.

No description available.

No description available.

No description available.

Flavonoids are naturally occurring compounds that are consumed regularly in the diet. The property of flavonoids, which they are most commonly known for, is their antioxidant activity. Other potential pharmaceutical applications of flavonoids can be related to their enzyme inhibition, anti-allergic, anti-inflammatory, anti-microbial and anti-cancer properties. Lipases have been used effectively in the production of flavonoid ester derivatives that have shown both increased antioxidant and antimicrobial activity. Enzymatic esterifications of flavonoids are performed in organic solvents that increase substrate solubility of complex organic molecules. For the esterification of compounds in non-aqueous reaction conditions, vinyl esters are often preferred as substrates compared to carboxylic acids (which can be involved in reversible reactions, due to the formation of the by-product, water). In this study a group of vinyl esters of tert-butoxycarbonylated amino acid derivatives were synthesized to study alongside a range of commercially available vinyl esters. The synthesis of ester derivatives of naringin using a range of hydrolytic enzymes has been studied. A range of small to medium sized commercially available vinyl esters (C2- C10), as well as amino acid vinyl esters were selected for the biotransformations. For the esterification of naringin, small-scale reactions were carried out for 72 hrs and the reaction mixtures were analysed by HPLC. Lipases from the species Pseudomonas stutzeri, Candida antarctica and Alcaligenes spp. performed more than 80% conversion of naringin with some of the selected acylating agents. Reactions carried out with P. stutzeri lipase were scaled up to isolate the product of the biotransformation. None of the screened enzymes were successful in the acylation of naringin with the amino acid vinyl esters. Assays were carried out to compare the antioxidant activity of naringin and the synthesized derivatives. Two of the acyl derivatives showed a greater antioxidant activity in the reduction of Cu2+, compared to naringin. Aminoglycosides are antibiotics that have anti-bacterial properties. As well as their anti-bacterial properties some have been employed for their ability to suppress stop codons, which is a useful property in reducing symptoms of some hereditary disorders. In the present work attempts were made to derivatise an aminoglycoside by acylating it with the amino acid vinyl esters, using hydrolytic enzymes. Despite screening with various proteases in different solvents, the acylation of amikacin was not succesful during this investigation.

Biaryl atropisomers are common structural motifs in natural products but most importantly they are used as chiral ligands in asymmetric catalysis. Despite their utility, current methods to synthesise them are limited and lack generality. Often ligands such as QUINAP have to be synthesised as the racemate and are resolved using stoichiometric palladium which is expensive and time consuming. Biocatalytic synthesis of biaryl atropisomers offers a new alternative greener route to their production. A biocatalytic redox desymmetrisation of symmetrical biaryl diols using a mutant of galactose oxidase (M3-5) is reported. Desymmetrised biaryl atropisomers were produced in good to excellent ee and yield for a range of substrates. After the desymmetrisation a partial kinetic resolution increased the ee further as the minor enantiomer was converted to the dialdehyde. The first example of biocatalytic dynamic kinetic resolution to synthesise atropisomers asymmetrically has been developed. Freely rotating biaryl N-oxide aldehydes underwent reduction using a ketoreductase enzyme to give biaryl N-oxide products in excellent ee (96-99%). These products were found to be novel Lewis base organocatalysts for the asymmetric allylation of benzaldehyde derivatives.

No description available.

No description available.

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.

Increasing demand for chiral technology in industry has led to the rapid development of catalysts for enantioselective processes. In this respect biocatalysts are of particular interest due to their excellent regio- and stereo- selectivity and their ability to work under mild conditions. The development of catalysts for the selective oxidation of alcohols to aldehydes and ketones represents a major challenge in organic synthesis. Previous work showed that a variant of the enzyme galactose oxidase (GOase) was capable of oxidising a wide range of chiral secondary alcohols with high enantioselectivity. The aim of this work is to develop new applications for this variant. Two new stereoselective processes have been developed employing this variant: 1. Enzymatic desymmetrisation of proatropisomeric diaryl ethers and biaryls. Atropisomers are stereoisomers resulting from restricted rotation about an axis, where the rotational barrier is high enough for isolation of the conformers. Desymmetrisation by GOase has allowed the production of atropisomers with enantiomeric excess (ee) up to 99% in good yields. An alternative approach based upon asymmetric reduction of the corresponding dialdehyde using ketoreductases (KREDs) has also been explored. 2. Deracemisation of racemic secondary alcohols by a combination of enzyme and transition metal catalysts. Deracemisation is a method for the production of enantiopure compounds starting from racemic substrates. Combination of the enzyme GOase and a transition metal catalyst has allowed the production of a single enantiomer of a number of secondary alcohols from the corresponding racemic mixture (ee > 99%, yield > 98%). Primary amides are widely applied in the polymer industry. They are produced in large quantities each year. An efficient solvent-free process (yield > 90%) for the production of erucamide has been developed employing immobilised Candida antarctica Lipase B (CALB, Novozym® 435 ) under mild conditions (solid ammonia source, 90 °C).