The Ellagitannins

Naturally occurring esters of hexahydroxydiphenic acid and dehydro-hexahydroxydiphenic acid are all presumed to be derived by in vivo oxidative and tautomeric transformations of bisgalloyl esters. The bio-genetic framework within which they are created in plants has been outlined and in the sense that these acids bear a formal relationship to gallic acid this is illustrated in Table 9. 

Number of gallic acid molecules Formal chemical relationship Phenolcarhoxylic acid Hydrolysis products of esters Ref. 

+2H2O Hydrated chebulic acid Chebulic acid (Split acid) 27, 28. 82. 92) 

+2H2O Trilloic acid Trilloic acid trilactone 50) 

Corilagin (28) Terminalia chebula P-l-o-galloyl R-( + )-hexahydroxydiphenic acid linked 3,6 D-glucopyra-nose conformation — 1b 32. 71. 73) 

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This complex tannin is formed during the aging process of red wine, whereby the catechin unit originates from the grapes, and the ellagitannin, in this case vescalagin, originates from the oak barrels. 

Niemetz, R., and Gross, G. G., 2003, Oxidation of pentagalloylglucose to the ellagitannin, tellimagrandin II, by a phenol oxidase from Tellima grandiflora leaves, Phytochem. 62 301-306. 

Wilson and Hagerman (1990) described an alternative spectrophoto metric procedure to quantify ellagic acid. This method has three advantages over the procedure developed by Bate-Smith (1977) 1) it is not sensitive to gallic acid, which can result in an overestimate of the ellagitannin content, 2) it is more sensitive, and 3) it is more convenient because oxygen does not interfere with the reaction. 

Some natural compounds offer a chiral structural backbone that biases the outcome of the oxidative coupling of appended aryls (e.g., the ellagitannins). It was plausible to suppose, therefore, that two aryl units could be linked by a non-natural chiral tether to induce atrop-selective coupling upon exposure to an appropriate oxidant. In one of their attempts to realize the total synthesis of calphostin D (200) [136], Merlic and co-workers showed that, in the presence of dioxygen in trifluoroacetic acid (TFA), the precursor 198 affords the coupled compound 199 as a single diastereoisomer. Unfortunately, the relative configuration was incorrect for the calphostin target (Scheme 49). 

A serendipitous use of a chiral auxiliary in atrop-selective biaryl bond formation has recently been published by Kita and co-workers [39, 137]. With diaryl substrate 201, which is related to precursors of the ellagitannins (see Section 14.6.1), PIFA-mediated oxidative coupling did not lead to the expected ellagitannin structure 202 (Scheme 50). Rather surprisingly, this reaction proceeds with intermolecular Ar-Ar bond formation. The chiral glucose framework efficiently transfers stereochemical information, but not in a intramolecular closure. 

Hager, T.J. Howard, L.R. Prior, R.L. 2010. Processing and storage effeets on the ellagitannin composition of processed blackberry products. J. Agric. Food Chem. 58 11749-11754. 

Ito, H. 2011. Metabolites of the ellagitannin geraniin and their antioxidant activities Planta Med [Published online Feb. 3, 2011.]. 

Oxidative biomimetic aryl coupling reactions of electron-rich (phenolic) aromatic hydrocarbons have occasionally been reported for selected examples see the reviews by Bringmann et al. [93 a] and the review on the ellagitannin chemistry by Quideau and Feldman [93b]. Oxidative homocoupling has also been achieved with palladium(II) acetate via the 5-arylpalladium complexes [78 d], but stoichiometric amounts of the palladium reagents are often required and acetylation can occur as a side reaction [93a]. 

The ellagitannin composition of extracts from the duramen depends on the species of oak. All four monomeric and four dimeric (roburin A, B, C, and D) ellagitannins are present in the three species of European oak, while the American species have practically no dimers. 

Analysis of toasted oak extracts shows a breakdown of the ellagitannins, especially after medium toasting (Table 13.19). This is related to the fusion temperatures of a blend of vescalagin and castala-gin (163°C) and gallic acid (250°C). Ellagic acid only reacts at higher temperatures (F > 450°C), but it is not very soluble in dilute alcohol solutions. 

R380 H. Ito, Metabolites of the Ellagitannin Geraniin and Their Antioxidant Activities , Planta Med., 2011, 77, 1110. 

Masson, G., Puech, J.-L. Moutounet, M. (1994). Localization of the ellagitannins in the tissues of Quercus robur and Quercus petraea woods. Phytochemistry, 37,1245-1249. 

Niemetz, R. Gross, G.G. (2003a). Oxidation of pentagalloylglucose to the ellagitannins, telhma-grandin II, by a phenol oxidase fiom Tellima grandifhra leaves. Phytochemistry, 62, 301-306. 

On the other hand, berry bioactive have many roles in cancer prevention and certain berries are considerably more effective than others. For example, the most active components in raspberry were the ellagitannins, but these components break down readily and the resultant products, including ellagic acid, may be the actual active components (Ross et al. 2007). Roles in cancer prevention include protection... 

No evidence has yet been obtained to show that dimeric products are formed by oxidative coupling of the monomeric species such as was noted in Class 2B (vide supra). However, brief comment should be made on two phenolic metabolites, isolated early in the studies of the ellagitannins chebulinic acid (91,140) and chebulagic acid (91) (Table 7.2.9). It is clear from biogenetic considerations that these are phenolic metabolites very probably derived by further oxidative ring fission of one aryl ring in a precursor such as geraniin (51). 

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