Flavan-3-ols structures

Earlier proposals (12, 13, U) and the results of biosynthetic experiments (18) have been adumbrated into a scheme of biosynthesis for the procyanidins (Figure k) in which it is suggested that they are formed as byproducts during the final stage of the synthesis of the parent flavan-3-ol structures, (+)-catechin and (-)-epicatechin (11, 18). A two step reduction of the f1av-3-en-3-ol... 

Figure 6.2. Compounds formed in wines during aging (a) structure with direct linkage between anthocyanin and flavan-3-ol proposed by Somers (1971) and (b) the anthocyanin-flavan-3-ol structure with an ethyl bridge proposed by Timberlake and Bridle (1976).

The structural diversity of procyanidins is based on the two possible monomer units (+)-catechin and (-)-epicatechin, on the different types of interflavanoid bonds and on the different lengths of chains which are possible. Besides the most common C4—>C8 and C4—>C6 linkages doubly linked flavan-3-ol structures exist, too. In addition to a C4- C8 bond they are linked by an ether bond between 07—>C2 [1] (see Fig. (3)). Cyclic structures have been proposed for procyanidins from kaki (Diospyros kaki) [12] and cherry (Primus avium) [13]. Higher molecular weight procyanidins are usually of moderate size (up to 3 000 daltons) [14], but also polymers with very high molecular weights (20 000 to ISO OOO... 

On the other hand, the flavan-3-ol units can also be doubly linked by an additional ether bond between C2 07 (A-type). Structural variations occurring in proanthocyanidin oligomers may also occur with the formation of a second interflavanoid bond by C-0 oxidative coupling to form A-type oligomers (Fig. 3) [17,20]. Due to the complexity of this conversion, A-type proanthocyanidins are not as frequently encountered in nature compared to the B-type oligomers. 

Flavonoids are a complex group of polyphenolic compounds with a basic C6-C3-C6 structure that can be divided in different groups flavonols, flavones, flavanols (or flavan-3-ols), flavanones, anthocyanidins, and isoflavones. More than 6,000 flavonoids are known the most widespread are flavonols, such as quercetin flavones, such as lu-teolin and flavanols (flavan-3-ols), such as catechin. Anthocyanidins are also bioactive flavonoids they are water-soluble vegetable pigments found especially in berries and other red-blue fruits and vegetables. 

RP-HPLC has also been used for the analysis of flavan-3-ols and theaflavins during the study of the oxidation of flavan-3-ols in an immobilized enzyme system. Powdered tea leaves (20Qmg) were extracted with 3 X 5 ml of 70 per cent aqueous methanol at 70°C for lQmin. The combined supernatants were filtered and used for HPLC analysis. Flavan-3-ols were separated in a phenyl hexyl column (250 X 4.6 mm i.d. particle size 5 /im) at 30°C. Solvents A and B were 2 per cent acetic acid in ACN and 2 per cent acetic acid in water, respectively. Gradient elution was 0-lQmin, 95 per cent B 10-4Qmin, to 82 per cent B to 40-5Qmin 82 per cent B. The flow rate was 1 ml/min. Theaflavins were determined in an ODS column (100 X 4.6 mm i.d. particle size 3pm) at 30°C. The flow rate was 1.8 ml/min and solvent B was the isocratic mobile phase. The data demonstrated that flavan-3-ols disappear during the oxidation process while the amount of theaflavins with different chemical structures increases [177],... 

Fig. 2.112. The structures of the flavan-3-ol(4a — 8)pelargonidin 3-0-/f-glucopyranosides (1-4) isolated from strawberry extract. The letter A denotes the aglycone ring systems belonging to the anthocyanidin substructure, whereas the letter F denotes the aglycone ring system belonging to the flavanol substructure. Reprinted with permission from T. Fossen et al. [252].

Fig. 2.113. Structures of monomeric flavan-3-ols and procyanidin oligomers in apples. Reprinted with permission from A. Yanagida et al. [253].

Poncet-Legrand, C. et ak, Flavan-3-ol aggregation in model ethanolic solutions incidence of polyphenol structure, concentration, ethanol content and ionic strength. Langmuir 19, 10563, 2003. 

Edelmann, A. et al., Dynamic light scattering study of the complexation between proline rich proteins and flavan-3-ols influence of molecular structure, polyphenol/protein ratio and ionic strength. In Oenologie 2003 (eds A. Lonvaud-Funel, G. De Revel, and P. Darriet), Tec et Doc, Arcachon, 2003, p. 408. 

The probutinidins (see Section 11.2) represent a second class of proanthocyanidins with flavan chain-extension units. Only five members of this class of compounds have been identified (Table 11.14). Their structures and absolute configurations were also confirmed by synthesis via reduction of the flavanone, butin, followed by acid-catalyzed condensation with the appropriate flavan-3-ol. A notable feature of the synthetic studies was the apparent preference for (4 8) bond formation reported by both groups of authors. 

Investigations of the conformational properties of the flavan-3-ols and oligomeric proanthocyanidins have hitherto involved a variety of molecular mechanics and molecular orbital computations in combination with crystal structures, time-resolved fluorescence, as well as and NMR methods. Representative references to all these techniques may be found in the papers listed in Refs. 241-247, 250. These NMR papers incidentally also represent the major contributions regarding the conformation of proanthocyanidins, and may be summarized in a conformational context by reference to the significant contributions of Hatano and Hemingway. 

Figure 11.3.5 Structure of flavan-3-ols. Chiral centers indicated by asterisks. G, galloyl.

Flavan-3-ols represent the most common flavonoid consumed in the American and, most probably, the Western diet and are regarded as functional ingredients in various beverages, whole and processed foods, herbal remedies, and supplements. Their presence in food affects quality parameters such as astringency, bitterness, sourness, sweetness, salivary viscosity, aroma, and color formation [Aron and Kennedy, 2007]. Flavan-3-ols are structurally the most complex subclass of flavonoids ranging from the simple monomers ( + )-catechin and its isomer (—)-epicatechin to the oligomeric and polymeric proanthocyanidins (Fig. 1.10), which are also known as condensed tannins [Crozier et al., 2006b]. 

Figure 2.1 Structure of flavan-3-ol monomers and dimers. (A)(—)-Epicatechin with = OH and R2 = H or ( + )-catechin with Ri = H and R2 = OH , (B) procyanidin (4p - 8)-dimer (C) procyanidin (4p -> 6)-dimer.

Verstraeten SV, Keen CL, Schmitz HH, Fraga CG, Oteiza PI. 2003. Flavan-3-ols and procyanidins protect liposomes against lipid oxidation and disruption of the bilayer structure. Free Radic Biol Med 34 84-92. 

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