Exploring hetero-atom derivatization in maltols and flavonols : the effect on reactivity of flavonol dioxygenation.

Flavonols are a class of polyphenolic natural products containing a 3-hydroxy pyrone core. They have been found to have several desirable properties such as anti-fungal, anti-bacterial, anti-mutagenic and anti-carcinogenic properties and they act as UV filters in plants. Flavonols display dual excitation-emission manifolds due to their ability to undergo excited state intramolecular proton transfer (ESIPT). Their photophysical and photochemical properties have aided in their them finding applications as fluorescence probes for various analytes. Bacteria and fungi have evolved to fight the anti-microbial effects of flavonols with the use of metalloenzymes called Quercetin Dioxygenases (QDO) named after the most ubiquitous flavonol, quercetin. In the presence of oxygen, QDOs break down flavonols to a depsidic product along with the evolution of CO; this reaction is called dioxygenation reaction. Model QDOs have been studied to probe flavonol dioxygenation, though of note, all the reported model QDOs are bidentate to the flavonol. In this dissertation, we probe the question of dioxygenation mechanism by functionalizing flavonols and studying the effect of this hetero-atom derivatization on dioxygenation reactivity of free flavonols and metal bound flavonolates. We also explore the effect hetero-atom derivatization has on flavonol and metal-flavonolate nitroxygenation, a reaction analogous to dioxygen wherein O2 is replaced with HNO. Maltol is a natural product that also contains a 3-hydroxy pyrone core. Initially isolated from the bark of larch trees, maltol has found extensive use in the food industry as a food additive as well as in the cosmetics industry as a fragrance material. Maltol acts as a bidentate ligand and several divalent maltolate complexes have found uses in the biomedical field, such as iron mimetics, insulin mimetics, contrasting agents, etc. Thio-containing derivatives have been synthesized and studied by the Farmer Group and the Cohen Group. In this work, we demonstrate the synthesis of stable pyrylium ylides via the alkylation of heteroatom maltol derivatives. These stable pyrylium ylides are susceptible to [5+2] cycloaddition reactions and ring substitutions. We successfully isolate monodentate hetero-maltolate complexes and propose a reaction scheme to access similar monodentate hetero-flavonolate complexes which can then be studied as model QDOs.