Polyphenolic ellagitannins and gallotannins: Structures, synthesis and biological activity - from folk medicine to chemical biology via wine sciences

Abstract

Hydrolyzable tannins constitute a class of plant bioactive polyphenols primarily composed of ellagitannins and gallotannins derived from the metabolism of gallic acid. Ellagitannins feature galloyl units esterified to a sugar core, usually glucose, and characterized by the presence of biaryl and diaryl ether bonds between some or all of their galloyl units.[1] Among ellagitannins, there exists a subclass of structurally unique nonahydroxyterphenoyl (NHTP)-bearing C-glucosidic molecules featuring an open-chain glucose core and exemplified by vescalagin. The fact that some of these C-glucosidic ellagitannins are found in wine as a result of aging of this beverage in oak-made barrels provided us with the impetus to examine their chemical reactivity and biological activity. Indeed, during aging in oak barrels, the hydroalcoholic and slightly acidic (i.e., pH 3–4) wine solution enables the solid-liquid extraction of these ellagitannins. Once in the wine solution, some of these natural products such as vescalagin can capture grape-derived nucleophilic entities such as the flavanols catechin and epicatechin and the anthocyanin oenin to furnish condensation products, some of them having been postulated as active principles in Asian herbal medicines.[2] Of pharmacological importance is the fact that several of these found-in-wine ellagitannin hybrids are much more potent than etoposide (VP-16) at inhibiting in vitro the anti-cancer target DNA topoisomerase IIa.[2a,b] Furthermore, we recently discovered that vescalagin is capable of drastically perturbing the actin cytoskeleton by interacting selectively with the actin filaments, both in vitro and in cellulo.[3] Moreover, gallotannins, in which galloyl units and/or depsidically-linked chains of galloyl units are usually esterified to a glucopyranose core, and some of their simpler precursors exhibit some interesting properties with possible applications as antifibrillogenic agents. Thus, the various biophysico-chemical properties we unveiled for these hydrolysable tannins will be presented and their exploitation in the development of therapeutic agents discussed during this lecture.