Chemistry of amine oxides

Tertiary N-methylamine-N-oxides are important intermediates and targets in organic syntheses. In addition, they are used on an industrial scale, e.g., as cellulose solvents (Lyocell fibers), surfactants and cosmetic additives. The discovery of two novel reactions of tertiary amine oxides, deoxygenative demethylation and deoxygenation with oxygen transfer, opened the way into a new field of amine oxide chemistry. The proposed project focuses on the elaboration of general synthetic procedures based on those two reactions, as well as their application to synthetic tasks in the field of alkaloid and vitamin E chemistry. This requires comprehensive studies of the underlying reaction mechanisms. Replacement of N-methyl groups by other substituents significantly increases the activity of many alkaloid drugs. The cleavage step, however, has proven to be extremely difficult to accomplish by conventional means. The new deoxygenative demethylation is expected to solve this problem, e.g., in the conversion of galanthamine, a potential Alzheimer medication. Deoxygenation with O-transfer allows to generate other selective oxidizing agents, so-called secondary oxidants, under mild conditions, which was hitherto impossible. This opportunity will be exploited for the synthesis of tocopherol (vitamin E) derivatives, which so far were only available in insufficient amounts for biological studies. With these compounds it should be possible to elucidate the formation pathway of secondary vitamin E metabolites. Furthermore, it will be possible for the first time to study the interaction of peroxynitrite, an important intracellular figure in chronic disease and immune response, with lipophilic vitamin E compounds in the absence of interference from aqueous reaction media.