The Application of Hydrolytic Enzymes for Biotransformations of Natural Products in Non-Aqueous Reaction Conditions

• Main Author: Bull, Joseph
• Other Authors: Littlechild, Jennifer
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: University of Exeter 2009
• Subjects: biocatalysis; lipases; Antarc*; Antarctica
• Online Access: http://hdl.handle.net/10036/76873

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 ...