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Chemistry of ortho-quinone methides

Project Leader
Rosenau Thomas, Project Leader
Duration:
01.01.2005-31.12.2007
Type of Research
Basic Research
Staff
Kloser Elisabeth, Co-worker (bis 21.02.2008)
Patel Anjan, Co-worker (bis 28.02.2011)
BOKU Research Units
Division of Chemistry of Renewable Resources
Funded by
Fonds zur Förderung der wissenschaftlichen Forschung (FWF) , Sensengasse 1, 1090 Wien, Austria
Abstract
ortho-Quinone methides (oQMs), a class of frequently occurring, but highly transient species, have been recognized as key intermediates in many biosynthetic and metabolic pathways. For example, the anti-carcinogenic properties of many natural products, such as the anthraquinones daunomycin or adriamycin, are based on their ability to form oQMs. Direct spectroscopic observation or analytical detection of oQMs was so far impossible due to their instability, so that their intermediacy was indirectly concluded from the presence of characteristic reaction or trapping products. Unfortunately, the use of oQMs in synthesis and their analysis is always hampered by their instability and short lifetime. One of the most prominent representatives of compounds readily forming oQMs is alpha-tocopherol, the main component of vitamin E, which has manifold physiological functions as lipophilic antioxidant, being used in a huge variety of medications, healthcare products, food additives, and cosmetics. Its oxidation pathways lead to an oQM intermediate both in vivo and in vitro. Even though alpha-tocopherol should in theory be able to produce two different oQMs upon oxidation, only a single one is formed with high regioselectivity. The same is observed for other vitamin E-type antioxidants. However, the cause of this reaction behavior is still unclear, which is amazing regarding the “popularity” of vitamin E.
Preliminary findings indicated that oQMs can be stabilized, thus significantly prolonging their lifetime (from seconds up to 20 min). Further elaboration can considerably expand scope and synthetic applicability of oQMs in general. Thus, it is the first goal of this project to develop the synthetic methodology for oQM stabilization and to apply the stabilized oQMs in exemplary syntheses, so that oQMs loose their undeserved reputation of being exotic and difficult to handle. Stabilization of oQMs can help, for instance, to clarify the action pathway of anti-cancerogenics, the process of protein/DNA alkylation by oQMs or the formation of vitamin E metabolites; in all cases the intermediate oQMs will loose their transience and can now be directly detected and manipulated. As a second project goal, a new hypothesis on the regioselectivity in oxidations of vitamin E-type antioxidants, which is based on strain in the heterocyclic ring as determining factor, has been put forward and must be verified experimentally and theoretically within this project. The new aspects of oQM chemistry, which are to be studied within this project, have the potential to evolve into versatile tools in organic synthesis, and will advance the understanding of the physiologically important vitamin E system.
Keywords
antioxidants; ortho-quinone methides; reaction mechanisms; regioselective oxidation; vitamin E;
Publications

** Adelwöhrer, C., Rosenau, T. Novel tocopherol compounds XX. 1,3,8-Trioxaphenanthrenes derived from g-tocopherol.

Tetrahedron, 61, 38, 9070-9074 WoS FullText FullText_BOKU

** Rosenau, T., Stanger, A. Synthesis and oxidation of "non-annulated" vitamin E-like compounds.

Tetrahedron Lett., 46, 45, 7845-7848 WoS FullText FullText_BOKU

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