Isolation, synthesis, and metabolism of polyphenols: Stilbenoids, gallotannins and ellagitannins.

摘要

The roles of dietary polyphenols, such as resveratrol found in red wine and grape seed extract, have become an increasingly more popular research topic. Dietary polyphenols have even achieved media success for their potential benefits on human health and disease. The success is frequently attributed to the compounds' antioxidant and reactive oxygen species (ROS) scavenging abilities. Not only are polyphenols highlighted as the benefitial health constituents of herbal remedies, but there are also two plant-polyphenol drugs approved by the United States Food and Drug Administration, Crofelemer (a proanthocyanidin oligomer from Croton lechleri) and Veregen (catechins from Camellia sinensis). Due to the demand for novel polyphenolic lead compounds, three major classes were chosen to be explored as part of this dissertation: stilbenes, gallotannins, and ellagitannins. The investigation of stilbenes includes an invited literature update on novel natural stilbenes, which have been isolated and identified since 2009. The review concludes by discussing the biological activities and potential health benefits of this polyphenol sub-class. Additionally, two new monomeric stilbenes, namely, vulpinoideols A and B, along with ten known compounds were isolated from a fox sedge (Carex vulpinoidea) acetone seed extract. All of the isolates were evaluated for their tyrosinase enzyme inhibitory activity, along with the well-known competitive inhibitor, arbutin. A synthetic route for naturally isolated gallotannins, namely, maplexins F and J, previously isolated from red maple (Acer rubrum) tree bark, was developed. Additionally, the ligand-enzyme interaction between the gallotannins and their target enzyme, alpha-glucosidase, was evaluated using biophsyical tools including isothermal titration calorimetry (ITC), fluorescence, and circular dichroism (CD) spectroscopic methods. Finally, a synthetic route was also developed for the ellagitannin gut-microbial metabolites, urolithins (dibenzopyranone derivatives), along with analytical UFLC-MS/MS methods to study the cellular and tissue uptake of the urolithins, as well as other dietary polyphenolic metabolites of interest.