Structure of Flavan-3-ols

Runge first isolated catechins (i.e., epicatechin) (22) from Acacia catechu in 1821 but it wasn t until the 1920s that Freudenberg made progress in the elucidation of the structures of these compounds (115, 377). Their general constitution as 5,7,3, 4 -flavan-3-ols was not established until 1925 (115). The absolute stereochemistry of catechin and epicatechin was finally established by Birch et al. (22) and Hardegger et al. (131) in 1957. 

Because of the importance of the shape of proanthocyanidins to many of their properties, the conformation of the heterocyclic ring is currently of interest. Engel et al. (95) examined the crystal structure of 8-bromo-5,7,3, 4 -tetra-0-methylcate-chin and established that both the heterocyclic oxygen and C-4 lie slightly above the mean plane of the adjacent aromatic ring and that C-2 lies well above (i.e., 60 pm) and C-3 lies below (-23 pm) this plane. The heterocyclic ring in this com- 

The structure of penta-O-acetyl-catechin is an interesting example of problems encountered in definition of the conformation of these compounds. In the crystal state, the heterocyclic ring is in a reverse half-chair conformation with both the 5-ring and 3-acetoxy substituents in axial positions (120). However, the heterocyclic ring proton coupling constants 2,3 = h,4a - and 

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

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.

Structure of Flavan-3-ol a Repeat Unit Contained in Polyflavonoid Tannin Extracts (source ref. [80])... 

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],... 

Nonhydrolyzable or condensed tannins are also named proanthocyanidins. These are polymers of flavan-3-ols, with the flavan bonds most commonly between C4 and C8 or C6 (Figure 6-23) (Macheix et al. 1990). Many plants contain tannins that are polymers of (+)-catechin or (-)-epicatechin. These are hydrogenated forms of flavonoids or anthocyanidins. Other monomers occupying places in condensed fruit tannins have trihydroxylation in the B-ring (+)-gallocat-echin and (-)-epigallocatechin. Oligomeric and polymeric procyanidins are formed by addition of more flavan-3-ol units and result in the formation of helical structures. These structures can form bonds with proteins. 

For analyzing molecular sizes of proanthocyanidins, depolymerization methods suffer from side reactions, such as epimerization and heterocyclic ring fission of flavan-3-ols. The depolymerization method estimates the average DP of proanthocyanidins in a mixture, but it is not able to determine the ratio of proanthocyanidins of different sizes. MALDI-TOF-MS is not able to analyze proanthocyanidins with a DP value higher than 12. The signal intensity of proanthocyanidins on MALDI-TOF-MS is not proportional to their amount, because proanthocyanidins of different sizes and structures differ in their... 

Anthocyanins are water soluble pigments responsible for the red to purple colour in plants. The common basic structure of all these compounds is the cation flavylium, which was proposed for the first time by Wilstaer in 1913 and later confirmed by Robinson in 1922. A special kind of flavonoids related to anthocyanins are the proanthocyanidins, also referred to as leucoanthocyanidins, in the case of monomeric proanthocyanidins, and condensed proanthocyanidins for the polymers of flavan-3-ols [32],... 

Condensed tannins in grapes and wine are more-or-less complex polymers of flavan-3-ols or cate-chins. The basic structural units are (-l-)-catechin and (—)-epicatechin (Figure 6.14). Heating these polymers in solution in an acid medium releases highly unstable carbocations that are converted... 

In the adsorption of some metal ion by tannin adsorbents [16], tannins are widely distributed in nature and have multiple adjacent phenolic hydroxyl groups and exhibit specific chelation ability toward metal ions [17]. According to the chemical structures of tannins, they can usually be classified into hydrolyzable tannins, condensed tannins and complex tannins. Hydrolyzed tannins yield gallic acid or eUagic acid when hydrolyzed by acid, base or some enzymes [18]. Turkish sumac tannin (hydrolyzable tannin) is illustrated in Fig. 28.1 whose basic structure is of flavan-3-ols. 

Depending on their structures, tannins are defined as hydrolyzable (gallotannins and ellagitannins) or condensed (monomers, dimers, oligomers, and polymers of flavan-3-ols). Condensed tannins are also known as proanthocyanidins [3,47]. Proanthocyanidins can be divided into propelargonidins, based on the hydroxylation pattern of the A- and B-rings [3]. Of these, procyanidins constitute the most common subclass of flavonoids in foods, and prodelphinidins and propelargonidins are also present [48,49]. 

Elaboration of oligomeric forms of procyanidins by the addition of flavan-3-ol units based on (— )-epicatechin (30) or (-I- )-catechin (3) leads to formation of two different helical structures. Those based on (— )-epicatechin (procyanidins 35 and 37) produce a left-handed helix, whereas those based on (+ )-catechin (procyanidin 38) form right-handed helices. 

Studies of the reactions of flavan-3-ols and particularly those of catechin have been central to the elucidation of the structure and development of uses for the condensed tannins. This work, initiated by Freudenberg and his colleagues at Heidelberg in the 1920s [see Weinges et al. (377) for a thorough review], continues to be an important aspect of condensed tannin chemistry. A wide range of electrophilic aromatic substitution reactions has been examined to obtain definitive evidence for the location of substitution (i.e. C-6 or C-8) of proanthocyanidins and to establish the influence of steric hindrance on the relative reactivity of these nucleophilic centers in flavan-3-ols. 

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. 

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].

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