The monoamine oxidase (MAO) enzyme is critical for the biological oxidation of monoamines. Although its mechanism of action has been extensively studied, it is not fully understood, with a lack of small molecule mimics being a major limitation. The MAO flavin active site exists in oxidised, semireduced radical and fully reduced forms. This talk describes the development of a flavin-catalysed amine oxidation that may have relevance to MAO activity.In the course of our studies on flavin catalysis in synthesis,1 we discovered flavinium catalyst 1 selectively oxidises amines using air as terminal oxidant. A key feature is the presence of alloxan 2 as co-catalyst, known for generating reactive oxygen species. We therefore believe alloxan acts as a radical mediator. A cysteine/methionine mimetic dialkyl sulfide is also required for catalysis. Figure 1. <img src='https://acs-archive-assets2.s3.amazonaws.com/241nm/uploads/70091_hooley_figure_1.jpg' alt='' />The radical nature of the reaction is supported by EPR spectroscopy and computational studies, showing semireduced flavin. We believe that transport of electrons proceeds sulfide�flavin�alloxan followed by radical chain reaction involving amine and O2. We propose a similar process in the enzyme; if so, the intimate presence of the sulfide moiety in the MAO active site may be of overlooked importance.2Murray, A. T.; Matton, P.; Fairhurst, N. W. G.; John, M. P.; Carbery, D. R. Org. Lett. 2012 , 14, 3656.Hendon, C. H.; Carbery, D. R.; Walsh, A. Chem. Sci. 2014 , 5, 1390.

Development of novel flavin-catalyzed reactions

248th National Meeting (2014)

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