The Chemistry of Wine Polyphenolic C-Glycosidic Ellagitannins Targeting Human Topoisomerase II

Polyphenolic nonahydroxyterphenoyl‐containing C‐glycosidic oak ellagitannins are found in wine as a result of the aging of this beverage in oak‐made barrels. Once in the slightly acidic wine (pH∼3–4), some of these complex natural products such as (−)‐vescalagin (1), but not its C‐1 epimer (−)‐casta...

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Bibliographic Details
Published in:Chemistry : a European journal 2005-11, Vol.11 (22), p.6503-6513
Main Authors: Quideau, Stéphane, Jourdes, Michael, Lefeuvre, Dorothée, Montaudon, Danièle, Saucier, Cédric, Glories, Yves, Pardon, Patrick, Pourquier, Philippe
Format: Article
Language:English
Subjects:
antitumor agents
Biphenyl Compounds - chemistry
Biphenyl Compounds - isolation & purification
Catechols - chemistry
Catechols - isolation & purification
Crystallography, X-Ray
ellagitannins
Glycosides - chemistry
Humans
Hydrolysis
Hydrolyzable Tannins - chemical synthesis
Hydrolyzable Tannins - chemistry
Hydrolyzable Tannins - pharmacology
Models, Molecular
Molecular Conformation
natural products
Phenols - chemistry
polyphenols
Structure-Activity Relationship
Topoisomerase II Inhibitors
Vitaceae
Wine
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Summary:Polyphenolic nonahydroxyterphenoyl‐containing C‐glycosidic oak ellagitannins are found in wine as a result of the aging of this beverage in oak‐made barrels. Once in the slightly acidic wine (pH∼3–4), some of these complex natural products such as (−)‐vescalagin (1), but not its C‐1 epimer (−)‐castalagin (2), can capture grape‐derived nucleophilic entities such as ethanol, the flavanols catechin (10 a) and epicatechin (10 b), the anthocyanin oenin (13 b), and the thiolic glutathione (16) to furnish condensation products with retention of configuration at the C‐1 locus. A computer‐aided rationale of this high diastereoselectivity is given. These condensation products can contribute to the modulation of organoleptic properties of the wine, as evidenced by the 23 nm bathochromic shift color absorbance observed with the novel oenin‐based anthocyano‐ellagitannin (15 b). Hydrolysis of 1 under solvolytic conditions furnished another novel compound that we refer to as vescalene (21), in addition to the known (−)‐vescalin (18). Of pharmacological importance is the fact that most of these found‐in‐wine water‐soluble ellagitannin derivatives are much more potent than etoposide (VP‐16) at inhibiting top2‐mediated DNA decatenation in vitro (top2=topoisomerase II)). The known (−)‐vescalin (18) and the novel vescalene (21) fully inhibited top2 at 10 μM concentration! The secrets of Bacchus! When wine is aged in oak‐made barrels, the oak‐derived polyphenolic C‐glycosidic ellagitannin (−)‐vescalagin can react with grape‐derived nucleophilic entities such as ethanol, the flavanols catechin and epicatechin, the anthocyanin oenin pigment and the thiolic glutathione to furnish condensation products in a diastereoselective manner (see scheme).
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.200500428