Molybdenum-containing oxidases and their application in cascade synthesis



McKenna, Shane
(2015) Molybdenum-containing oxidases and their application in cascade synthesis. Doctor of Philosophy thesis, University of Liverpool.

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Abstract

Molybdenum-dependent xanthine oxidoreducatases (XOR) are a family of well characterized enzymes which are known to oxidise purines, imines and aldehydes in cellular metabolism. Despite significant studies relating to drug metabolism, application to chemical synthesis is relatively unexplored.. Herein we report the first use of XORs in the cascade synthesis of carboxylic acids from activated and unactivated alcohols by the combination of the mutant alcohol oxidase GOaseM3-5 and XOR (E.coli XDH & PaoABC). Twenty five carboxylic acids were obtained in quantitative conversion and the methodology compares very well with state-of-the-art catalytic chemical oxidation methods. The reactions were performed in water at ambient temperature and pH using oxygen as the terminal oxidant with the only by-product being H2O2. The oxidation system was also applied to the synthesis of the biomass-derived platform chemical FDCA starting from HMF. The biocatalysts used were able to tolerate a substrate concentration of 100 mM, 20 times higher than previous reported methods with 74% isolated yield of FDCA. Although XORs exhibited a wide substrate scope, no chiral selectivity could be demonstrated. The application of XOR enzymes was also demonstrated in the synthesis of lactams from amino alcohols via an in situ generated imine intermediate. Although pyrrolidone was obtained in 85% yield from its corresponding amino alcohol, longer chain amino alcohols were not well tolerated with either poor or no conversion observed. Although currently limited in substrate scope, this novel biomimetic oxidative cyclisation represents an interesting synthetic approach to lactams, found in a wide variety of biologically interesting target molecules.

Item Type: Thesis (Doctor of Philosophy)
Divisions: Fac of Science & Engineering > School of Chemistry
Depositing User: Symplectic Admin
Date Deposited: 25 Aug 2016 08:08
Last Modified: 25 Aug 2016 08:08
URI: http://livrepository.liverpool.ac.uk/id/eprint/2045359
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