**2. General classification and biosynthesis of flavonoids**

Associated to these biological properties, these plants are chemically composed by different classes of metabolites including steroids, organic acids, chromenes, diterpenes, triterpenes, polyphenols, tannins, anthraquinones, alkaloids, and flavonoids, which comprise the natural

Besides these compounds, species from the genus *Caesalpinia* interestingly produce unusual compounds such as uncommon biflavonoids and a rare subclass of flavonoids, named homoi‐ soflavonoids. The first group is more distributed within plants, while homoisoflavonoids are restrict only to some vegetal species including those from Fabaceae and Asparagaceae [6]. These compounds are also encountered, although less common, in other families as Gentianaceae, Polygonaceae, Portulacaceae, and Orchidaceae. There are two different work concerning about homoisoflavonoids, which relate the existence of approximately 240 natu‐

In this sense, it is important to define the general characteristics of flavonoids, once they are the core subunits of biflavonoids and cover the rare class of homoisoflavonoids. In general, flavonoids are low molecular weight polyphenols, brightly colored due to their absorptions of UV light, and the most common structures are associated to antioxidant properties [8–10]. Flavonoids, classified as phytoalexins, are produced as a response to microbial infection in plants. They have a notorious participation into the scientific scenario due to the beneficial association to the humans' daily basis intake of nutrients as functional foods improving

The consumption of functional foods, or nutraceuticals, is strongly associated to these com‐ pounds. In addition, the ingestion of flavonoids from functional foods implicates in lowering blood triglycerides and homocysteine, decreasing blood pressure, acting against inflammatory, platelet antiaggregation processes, and the improvement of endothelial function [11]. These compounds are also associated to another range of biological properties lowering the incidence of cancer, including prostate, stomach, breast, and lung cancers [12]. In addition, various pro‐ tective effects of flavonoids have demonstrated them as important multi‐target agents [13, 14]. In that regard, the genus *Caesalpinia* is considered a rich source of common flavonoids. However, this genus is also associated to unique biflavonoids constituted by homoisofla‐ vonoids subunits and a considerable amount of representatives from the class of naturally occurring homoisoflavonoids. Up to date, there are reports pointing to the existence of about

An interesting point is that homoisoflavonoids can also be found as dimers. Biflavonoids com‐ pounds are dimers of flavonoids assembled in diverse manners by different species. The number of possibilities for these structures (involving all classes of flavonoids) points to more than 20,000 different molecules. However, not all these have been encountered in nature so far, summing to 500 representatives [15]. From these, less than 10 are constituted by homoisoflavonoids subunits. As homoisoflavonoids and their dimers from the genus *Caesalpinia* are unique compounds, this chapter proposes to gather the available data from the literature in a systematic overview associating them to biological properties aiming to demonstrate these compounds as notable

representatives composing the chemical space associated to natural products.

product diversity of this genus.

98 Flavonoids - From Biosynthesis to Human Health

rally occurring compounds [6, 7].

240 naturally occurring homoisoflavonoids [6, 7].

human health [8, 10].

The classification of flavonoids consists in two main groups, the 2‐phenylchromans and the 3‐phenylchromans. Compounds presenting the 2‐phenylchroman core, in which the aromatic ring B is connected to C‐2 atom, include flavonols, flavanones, flavan‐3‐ols, flavones, antho‐ cyanins, and proanthocyanidins. On the other hand, compounds with the 3‐phenylchroman group, in which the aromatic ring B is connected to C‐3 atom, include isoflavonoids named isoflavones, isoflavans, and pterocarpans. Another group, named neoflavonoids, in which the benzene ring B is connected to C‐4 atom, is less common. There are cases in which the ring C occurs as an isomeric form presenting a five‐membered ring, which is associated to the forma‐ tion of aurones. Another class of phenolic compounds, named chalcones, is not considered true flavonoids due to their lack on the aromatic C ring but still considered members of the flavonoids family. In the same way, a closely related group compounds, the stilbenes, are important due to their biological potential [16]. A brief representation of each class of flavo‐ noids and their sources is demonstrated in **Figure 1**.

**Figure 1.** Classification of flavonoids, general structures, examples, and biological sources.

These structures are important for the recognition and classification of biflavonoids moieties, once they could exist as complex structures presenting aurones, isoflavonoids, neoflavonoids, chalcones, and other moieties as well as dimers of homoisoflavonoids.

Flavonoids are products from the phenylpropanoid building block cinnamoyl‐CoA, in which chain extension is provided by three units of malonyl‐CoA [17]. Cinnamoyl‐CoA is derived from the amino acids phenylalanine and tyrosine which are converted by phenylalanine and tyrosine ammonia lyases to cinnamic acid and *para*‐hydroxycinamic acid, respectively [18]. The aromatic polyketide formed from the union of cinnamoyl‐CoA and three units of malonyl‐ CoA might form the benzo‐γ‐pyrone nucleus containing aromatic rings A, B, and a heterocy‐ clic ring C, substituted or not. This nucleus is precursor of a great number of flavonoids. In this sense, flavonoids are characterized by the classic flavan nucleus presenting a C<sup>6</sup> ‐C<sup>3</sup> ‐C<sup>6</sup> skeleton. In addition, chalcones might undergo different cyclization with the addition of a single carbon, provided by S‐methyl moiety of methionine, which lead to the formation of the homoisofla‐ vonoid nucleus, which can be converted to the other classes of homoisoflavonoids (**Figure 2**).

**Figure 2.** Biosynthetic scheme for the formation of a flavonoid nucleus (monomeric structure of biflavonoids) and the formation of the existing types of homoisoflavonoid nucleus.
