Proanthocyanidin Polymerization

The biosynthesis of the proanthocyanidins is believed to proceed by addition of an electrophilic extension unit derived from a flavan-3,4-dioP or a flavan-3-oP to a nucleophilic starter unit, most likely a flavan-3-ol, with sequential addition of further chain-extension units. Although the genetics of interflavanyl bond formation in the proanthocyanidin polymerization process are not yet defmed, " the search for the elusive condensing enzyme continues unabated. ... 

In spite of the recent progress in understanding the biosynthesis of the major building blocks of proanthocyanidins, (-l-)-catechin and (-)-EC, some important questions still remain to be elucidated (e.g., the exact nature of the molecular species that undergo polymerization and the mechanisms of assembly). The biosynthetic pathways for proanthocyanidins have been extensively reviewed [23-28]. A general scheme summarizing proanthocyanidin biosynthesis adapted from [27] and [28] is reported in Fig. 5. 

SAR studies were carried out by de Bruyne et al. [92] on a series of dimeric procyanidins, considered as model compounds for antiviral therapies. On the whole, proanthocyanidins containing EC dimers exhibited more pronounced activity against herpes simplex virus (HSV) and human immunodeficiency virus (HIV), while the presence of ortho-trihydroxyl groups in the B-ring appeared to be essential in all proanthocyanidins exhibiting anti-HSV effects. Galloylation and polymerization reinforced the antiviral activities markedly. 

Flavan-3-ols orflavanols have a saturated three-carbon chain with a hydroxyl group in the C3 position. In foods they are present as monomers or as proanthocyanidins, which are polymeric flavanols (4 to 11 units) known also as condensed tannins. In foods they are never glycosylated. 

Proanthocyanidins (PAs), also known as condensed tannins, are oligomeric and polymeric flavan-3-ols. Procyanidins are the main PAs in foods however, prodelphinidins and propelargonidins have also been identified (Gu and others 2004). The main food sources of total PAs are cinnamon, 8084 mg/100 g FW, and sorghum, 3937 mg/100 g FW. Other important sources of PAs are beans, red wine, nuts, and chocolate, their content ranging between 180 and 300 mg/100 g FW. In fruits, berries and plums are the major sources, with 213.6 and 199.9 mg/100 g FW, respectively. Apples and grapes are intermediate sources of PAs (60 to 90 mg/100 g FW), and the content of PAs in other fruits is less than 40 mg/100 g FW. In the majority of vegetables PAs are not detected, but they can be found in small concentrations in Indian squash (14.8 mg/ 100 g FW) (Gu and others, 2004 US Department of Agriculture, 2004). 

Flavanols and procyanidins Flavanols, or flavan-3-ols, are synthesized via two routes, with (+) catechins formed from flavan-3,4-diols via leucoanthocyanidin reductase (LAR), and (—) epicatechins from anthocyanidins via anthocyanidin reductase (ANR) (see Fig. 5.4). These flavan-3-ol molecules are then polymerized to condensed tannins (proanthocyanidins or procyanidins), widely varying in the number and nature of their component monomers and linkages (Aron and Kennedy 2008 Deluc and others 2008). It is still not known whether these polymerization reactions happen spontaneously, are enzyme catalyzed, or result from a mixture of both. 

Sun B, Leandro C, Ricardo JM (1998) Separation of grape and wine proanthocyanidins according to their degree of polymerization. J Agric Food Chem 46 1390-1396... 

Butler LG, Price ML, Brotherton JE (1982) VaniUin assay for proanthocyanidins (condensed tannins) modification of the solvent for estimation of the degree of polymerization. J Agric Food Chem 30 1087-1089... 

The second group of tannins are the condensed tannins, or polymeric proanthocyanidins (2). These are composed offlavonoid units, and are more recalcitrant to biodegradation than hydrolysable tannins. Of these, the... 

Souquet, J.-M. et al.. Polymeric proanthocyanidins from grape skins. Phytochemistry 43, 509,1996. 

Labarbe, B. et al.. Quantitative fractionation of grape proanthocyanidins according to their degree of polymerization. J. Agric. Food. Chem. 47, 2719, 1999. 

Czochanska, Z. et al., Direct proof of a homogeneous polyflavan-3-ol structure for polymeric proanthocyanidins. J. Chem. Soc. Chem. Commun. 375, 1979. 

Deprez, S., Brezillon, C., Rabot, S., Philippe, C., Mila, I., Lapierre, C., and Scalbert, A., Polymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular-weight phenolic acids, J. Nutr., 130, 2733, 2000. 

Achmadi, S. et al., Catechin-3-O-rhamnoside chain extender units in polymeric proanthocyanidins from mangrove bark. Phytochemistry, 35, 217, 1994. 

Dauer, A., Rimpler, H., and Hensel, A., Polymeric proanthocyanidins from the bark of Hamamelis virginiana, Planta Med, 69, 89, 2003. 

The two principal classes of proanthocyanidins found (10) in plant tissues are the procyanidins (1, R e H) and the prodeTphin-idins (1, R s OH). Proanthocyanidins of mixed anthocyanidin character (1, R = H or OH) have been noted. In any tissue where proanthocyan din synthesis occurs there is invariably found a range of molecular species - from the monomeric flavan-3-ols (catechins, gallocatechins) to the polymeric forms (1) and biosynthetic work (11) suggests a very close relationship between the metabolism of the parent f1avan-3-o1 and the synthesis of proanthocyanidins, Figure 4. 

The flavan-3-ols most occurring in nature are (+)-catechin and (-)-epicatechin (EC), although gallocatechin and epigallocatechin have also been identified [42]. Proanthocyanidins (or condensed tannins) include oligo- and polymeric forms of the monomeric flavanols and will be examined later. Polymerization of monomeric flavanols can occur as a result of auto-oxidation, but more often it is catalyzed by polyphenoloxidase (PPO), an enzyme that is present in most plant tissues [43]. 

Proanthocyanidins (PAs, syn condensed tannins) are polymeric flavan-3-ols whose elementary units are linked by C-C and occasionally C-O-C bonds (polymerization degree between 3 and 11), Fig. (12) [19]. 

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