2. Chemistry and classification of flavonoids

Flavonoids are a group of natural compounds with variable phenolic structures. In 1930, a new substance was isolated from oranges. At that time, it was believed to be a member of a new class of vitamins and was named as vitamin P. Posteriorly, it appeared that this compound was the flavonoid rutin and since then more than 9000 varieties of flavonoids have been identified [8].

Chemically, flavonoids are formed by a C6–C3–C6 structure, which consists of two benzene rings (A and B) linked by a three-carbon chain that form an oxygenated heterocycle (C ring) (Figure 1). They can be divided into nine classes according to their chemical structures: flavanones, flavones, dihydroflavonols, flavonols, flavan-3-ols, or flavanols [including monomers, proanthocyanidins, and flavanol-derived compounds (theaflavins and thearubigins)], anthocyanins, isoflavones, chalcones, and dihydrochalcones (Figure 2) [4]. The various classes of flavonoids differ in the level of oxidation and pattern of substitution of the C ring, while individual compounds within a class differ in the pattern of substitution of the A and B rings. Flavonoids in nature occur mostly as glycosides, aglycones (especially flavanols), and, in few cases, as methylated derivatives [3]. The basic flavonoid structure is the aglycone. When glycosides are formed, the glycosidic linkage is normally located in positions 3 or 7 and the

Figure 1. Basic flavonoid structure.

1. Introduction

372 Flavonoids - From Biosynthesis to Human Health

countries.

dietary flavonoid intake.

logical regulators, and cell cycle inhibitors [2].

2. Chemistry and classification of flavonoids

Flavonoids are ubiquitously distributed plant secondary metabolites, particularly in fruits, vegetables, legumes, nuts, chocolate, and derived beverages (e.g., tea, wine, and juices) [1]. They are synthesized through the phenylpropanoid pathway, converting phenylalanine into 4-coumaroyl-CoA, which then enter the flavonoid biosynthesis pathway. Finally, various enzymes modify the basic flavonoid skeleton, leading to the different flavonoid subclasses [2]. In plants, flavonoids fulfill many different functions, such as protecting against ultraviolet radiation and phytopathogens, and acting as pigments, chemical messengers, physio-

Over the last three decades, flavonoids have received a lot of attention in cellular and animal models due to their well-established biological properties such as antioxidant, anti-inflammatory, and anti-carcinogenic effects, especially inducing enzymes and modulating metabolic and cell signaling pathways [3]. However, the epidemiologic evidence on the reduction in the chronic disease risk is still limited and usually inconsistent [4, 5]. The strongest evidence of their health-protective effects is for cardiovascular diseases [6] and type 2 diabetes [7]. One of the potential explanations of these inconsistent results is the difficulty in accurately assessing dietary flavonoid intake and the large variability of flavonoid intake among populations/

This chapter is focused on the large differences in dietary flavonoid intakes and food sources worldwide, but prior to this, it is also important to briefly summarize the complexity of flavonoid chemistry and classification, and the different possible methodologies to assess

Flavonoids are a group of natural compounds with variable phenolic structures. In 1930, a new substance was isolated from oranges. At that time, it was believed to be a member of a new class of vitamins and was named as vitamin P. Posteriorly, it appeared that this compound was the flavonoid rutin and since then more than 9000 varieties of flavonoids have been identified [8].

Chemically, flavonoids are formed by a C6–C3–C6 structure, which consists of two benzene rings (A and B) linked by a three-carbon chain that form an oxygenated heterocycle (C ring) (Figure 1). They can be divided into nine classes according to their chemical structures: flavanones, flavones, dihydroflavonols, flavonols, flavan-3-ols, or flavanols [including monomers, proanthocyanidins, and flavanol-derived compounds (theaflavins and thearubigins)], anthocyanins, isoflavones, chalcones, and dihydrochalcones (Figure 2) [4]. The various classes of flavonoids differ in the level of oxidation and pattern of substitution of the C ring, while individual compounds within a class differ in the pattern of substitution of the A and B rings. Flavonoids in nature occur mostly as glycosides, aglycones (especially flavanols), and, in few cases, as methylated derivatives [3]. The basic flavonoid structure is the aglycone. When glycosides are formed, the glycosidic linkage is normally located in positions 3 or 7 and the

Figure 2. Flavonoid classes and their chemical structures.

sugar can be L-rhamnose, D-glucose, glucorhamnose, galactose, or arabinose [9]. This is very relevant because bioavailability differs among flavonoids, depending on the aglycone, the type of monosaccharide attached, and its position [10].
