Flavonoids, B-ring

The olives themselves contain many phenolic compounds with antioxidant properties. Bouaziz et al. (2005) investigated the olive cultivar Chemlali from Tunisia. Oleuropein (7.14), a bitter glycoside esterified with a phenolic acid, was the major compound present. Phenolic monomers and twelve flavonoids were also identified. The antioxidant activity of the extract was evaluated. Acid hydrolysis of the extract enhanced its antioxidant activity. / -Hydroxyphenyl-cthanol (7.12) and quercetin (1.43) showed antioxidant activities similar to that of 2,6-di-fert-butyl-4-methyl phenol (7.15), a reference compound with known antioxidant properties. It was suggested that a hydroxyl group at the ortho-position on the flavonoid B ring could contribute to the antioxidant activity of the flavonoids. 

P2. Pannala, A. S., Chan, T. S., O brien, P. J., and Rice-Evans, C. A., Flavonoid B-ring chemistry and antioxidant activity Fast reaction knetics. Biochem. Biophys. Res. Commun. 282, 1161-1168 (2001). 

The flavonoid compounds may be easily identified by their characteristic spectra in methanol since the majority exhibit a maximum in the long UV range (band I) between 325 and 400 nm, and a second maximum at shorter wavelengths (band II) between 240 and 295 nm. These two bands can be split into two maxima or a maximum and a shoulder or an inflection (Bla, Bib, Blla, and Bllb). In some cases it is possible to distinguish a supplementary maximum, shoulder, or inflection (band III) between 295 and 325 nm (Barberan et ah, 1985). The BI is associated with absorption of the flavonoid B-ring, which is associated with a ciimamoyl-nucleus, while the BII is associated with A-ring,which corresponds to a benzoyl-nucleus (Mabry et ah, 1970) (Figure 7.3). 

NADH-oxidase activity was based on the O2 uptake in the presence of complex 1 substrates (e.g., NADH) and is dependent on complexes 1, 111, and IV. Hydroxy-lation of the flavonoid B-ring was an important determinant of inhibitory potency toward NADH-oxidase [2]. The absence of B-ring hydroxyl substituents or their... 

Similar chemical reactions are involved in the reaction of other catechols such as the catecholamines, dopamine, and L-dihydroxyphenylalanine (L-DOPA) with cysteine or GSH [149-152] and can lead to the generation of mitochondrial toxins with relevance to Parkinson s disease [153-155], As well as possible cytotoxic effects of lowering cellular thiol levels or binding to cysteine residues at die active site of specific enzymes, flavonoids could act beneficially by acting to limit the formation of the potentially cytotoxic catecholamine-thiol adducts, in a manner similar to that observed for dihydro-lipoic acid [151], Because of the structural similarity of the flavonoid B-ring and their ability to donate electrons efficiently to form quinones, it is conceivable that specific flavonoids may be of use to prevent such neurotoxic compounds as 5-S-cysteinyl dopamine from forming in vivo. 

Sekher PA, Chan TS, O Brien PJ, Rice-Evans CA. Flavonoid B-ring chemistry and antioxidant activity fast reaction kinetics. Biochem Biophys Res Commun 2001 282 1161-1168. 

Fig. 16.6 The 1,3-diphenyl propane skeleton of flavonoids and the numbering system for flavonoids. Three structural features optimise the radical scavenging properties of a flavonoid (i) an orto-dihydroxy structure of the B-ring (catechol) (ii) 2,3 double bond in conjugation with a 4-oxo group (iii) 3- and 5-hydroxy groups (Bors and Saran, 1987).

Anthocyanins are colored flavonoids that attract animals when a flower is ready for pollination or a fruit is ready to eat. They are glycosides (i.e., the molecule contains a sugar) that range in color from red, pink, and purple to blue depending on the number and placement of substitutes on the B ring (see Fig. 3.7), the presence of acid residues, and the pH of the cell vacuole where they are stored. Without the sugar these molecules are called anthocyanidins. The color of some pigments results from a complex of different anthocyanin and flavone molecules with metal ions. 

In addition to the flavonoids with ring B attached to the C2 position of ring C, other types of flavonoids, particularly those with ring B attached to C3 (isoflavones), C4 (neoflavonoids), and open C ring (chalcones), have also been commonly found in fruits and vegetables. 

These structurally diverse compounds exhibit a range of biological activities in vitro that may explain their potential health-promoting properties, including antioxidant and anti-inflammatory effects and the induction of apoptosis (Hooper and others 2008). Most of the recent interest in flavonoids as health-promoting compounds is related to their powerful antioxidant properties. The criteria to establish the antioxidant capacity of these compounds is based on several structural characteristics that include (a) the presence of o-dihydroxyl substituents in the B-ring (b) a double bond between positions 2 and 3 and (c) hydroxyl groups in positions 3 and 5. 

Although no good quantitative correlation between redox potentials of flavonoids and their prooxidant activities still was not documented, a relationship between the prooxidant toxicity of flavonoids to HL-60 cells and redox potentials apparently takes place [176]. However, there is a simple characteristic of possible prooxidant activity of flavonoids, which increases with an increase in reactive hydroxyl groups in the B ring. From this point of view, the prooxidant activity of flavonoids should increase in the range kaempferol < quercetin < myricetin (Figure 29.7). Thus, for many flavonoids the ratio of their antioxidant and prooxidant activities must depend on the competition between Reactions (14) and (15) and Reaction (17). 

Stotz G, Forkmann G (1982) Hydroxylation of the B-ring of flavonoids in the 3 - and 5 -position with enzyme extracts from the flowers of Verbena hybrida. Z Natuforsch 37C 19-23... 

Eq. 2 V/S is the volume to surface ratio Phi, the torsion angle between the C2 atom and the B ring o, the Hammett coefficient of the B ring dV, volume difference between substrate and flavonoid dL, length of the C3 side chain (p, dipole moment and C3, C5, and C4 the electron density occurring at these atoms. 

LC UV is valuable for the identification of isoflavones since their spectra differ in absorption properties from most of the other flavonoids. They have a C2-C3 double bond, with the B-ring at C3, which prevents conjugation of the phenyl group with the pyrone carbonyl group. This reduces the contribution of the B-ring to the UV spectrum and results in a peak of very low intensity in the 300 to 330 nm range (band I). 

The first conventional mode of MS involves El ionization, in which the neutral flavonoid is impacted in the gas phase with an electron beam of 70 to 100 eV. Resulting mass spectra of the flavonoid aglycones are characterized by molecular ion peaks (M ), and fragment ions from both the A and B rings. The use of a reactant gas in the ionization chamber. Cl, normally results in the production of a more abundant molecular ion and simpler fragmentation patterns. General information about mass spectra of flavonoids recorded by these methods has been published by several authors. More specific mass spectra analyses... 

FIGURE 3.2 General phenylpropanoid and flavonoid bios5mthetic pathways. The B-ring hydroxylation steps are not shown. For formation of anthocyanins from leucoanthocyanidins two routes are represented a simplified scheme via the anthocyanidin (pelargonidin) and the likely in vivo route via the pseudobase. Enzyme abbreviations are defined in the text and in Table 3.1. 

The route to formation of flavonoids lacking 4 -hydroxylation of the B-ring has not been elucidated. However, one possible route is the direct use of cinnamate as a substrate by 4CL. Activity on cinnamate has been shown at low levels for some of the recombinant 4CL... 

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