Synthetic approaches to polyoxygenated chromone and chromanome natural products
The work described in this thesis is concerned with the chemistry of polymethoxylated aromatic carbonyl compounds bearing a 2,6-dioxygenated substitution pattern, with particular regard to establishing synthetic routes to biologically active chromone and chromanone systems. Syntheses of key intermediates in the approaches to the natural products stigmatellin, baicalein and LL-D253(x) (and related products) were undertaken. In chapter one the reactions of nucleophiles at the carbonyl moieties of 2,6- dioxygenated benzene carbonyl compounds are reviewed. This type of process can present special difficulties and was to prove particularly significant at various stages of the work described in subsequent chapters. Chapter two is a review of the provenance, abundance, biosynthesis, and previous syntheses of the natural products stigmatellin, baicalein and LL-D253(x), these being the targets of the synthetic work undertaken in the course of the project. Chapter three is concerned with an approach to a fragment of the stigmatellin molecule (referred to as stigmatellin fragment A) using the Vilsmeier formylation reaction, while chapter four is concerned with an alternative approach to stigmatellin fragment A using Friedel-Crafts acylation methodology. The strategies and the results obtained are described and analysed in detail. In chapter five a strategy for the synthesis of baicalein trimethyl ether is described and the results obtained are discussed.