Development of Novel Flavin - Catalysed Transformations

Abstract

Flavin catalysis has been developed as an environmentally benign route to novel redox chemistry, and the utility of these catalytic systems as simple models of flavoenzyme mechanism has been discussed. A system for oxidising aldehydes to carboxylic acids under flavin catalysis using a Bayer-Villiger type mechanism has been developed, which shows similarities to the enzyme bacterial luciferase. An oxidation of primary amines, using alloxan as co-catalyst and a sulfide as reducing agent, was developed. This was found to work efficiently using air as terminal oxidant, and by extensive mechanistic studies involving EPR spectroscopy, kinetics and UV/visible spectroscopy we propose a radical mechanism. The similarities in some kinetic properties of our system to monoamine oxidase (B isozyme) led us to re-evaluate some previously published pKa dependence data. The catalytic activity of alloxan itself was evaluated, in conjunction with a Cu(I) co-catalyst, and was found to be effective in oxidation of amines, including oxidative cross-coupling, as well as for diimide-like reductions of alkenes and alkynes with hydrazine. Finally, flavin-indole charge transfer chemistry was found to promote selective C3-deuteration of indoles. The CT complex was isolated and found to form a flavin-indole covalent bond under certain conditions. Additionally, we found that in situ DCl generation was a viable method for indole deuteration with very short reaction time and high selectivity compared to previous methods.

Date of Award	6 Jul 2015
Original language	English
Awarding Institution	University of Bath
Sponsors	GlaxoSmithKline
Supervisor	David Carbery (Supervisor)