Flavan-3-ols (sometimes referred to as flavanols) are a subgroup of flavonoids. They are derivatives of flavans that possess a 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton. Flavan-3-ols are structurally diverse and include a range of compounds, such as catechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, proanthocyanidins, theaflavins, thearubigins. They play a part in plant defense and are present in the majority of plants. [1]
The single-molecule (monomer) catechin, or isomer epicatechin (see diagram), adds four hydroxyls to flavan-3-ol, making building blocks for concatenated polymers (proanthocyanidins) and higher order polymers (anthocyanidins). [2]
Flavan-3-ols possess two chiral carbons, meaning four diastereoisomers occur for each of them. They are distinguished from the yellow, ketone-containing flavonoids such as quercitin and rutin, which are called flavonols. Early use of the term bioflavonoid was imprecisely applied to include the flavanols, which are distinguished by absence of ketone(s). Catechin monomers, dimers, and trimers (oligomers) are colorless. Higher order polymers, anthocyanidins, exhibit deepening reds and become tannins. [2]
Catechin and epicatechin are epimers, with (–)-epicatechin and (+)-catechin being the most common optical isomers found in nature. Catechin was first isolated from the plant extract catechu, from which it derives its name. Heating catechin past its point of decomposition releases pyrocatechol (also called catechol), which explains the common origin of the names of these compounds.
Epigallocatechin and gallocatechin contain an additional phenolic hydroxyl group when compared to epicatechin and catechin, respectively, similar to the difference in pyrogallol compared to pyrocatechol.
Catechin gallates are gallic acid esters of the catechins; an example is epigallocatechin gallate, which is commonly the most abundant catechin in tea. Proanthocyanidins and thearubigins are oligomeric flavan-3-ols.
In contrast to many other flavonoids, flavan-3-ols do not generally exist as glycosides in plants. [3]
The flavonoids are products from a cinnamoyl-CoA starter unit, with chain extension using three molecules of malonyl-CoA. Reactions are catalyzed by a type III PKS enzyme. These enzyme do not use ACPSs, but instead employ coenzyme A esters and have a single active site to perform the necessary series of reactions, e.g. chain extension, condensation, and cyclization. Chain extension of 4-hydroxycinnamoyl-CoA with three molecules of malonyl-CoA gives initially a polyketide (Figure 1), which can be folded. These allow Claisen-like reactions to occur, generating aromatic rings. [4] [5] Fluorescence-lifetime imaging microscopy (FLIM) can be used to detect flavanols in plant cells. [6]
Figure 1:Schematic overview of the flavan-3-ol (–)-epicatechin biosynthesis in plants: Enzymes are indicated in blue, abbreviated as follows: E1, phenylalanine ammonia lyase (PAL), E2, tyrosine ammonia lyase (TAL), E3, cinnamate 4-hydroxylase, E4, 4-coumaroyl: CoA-ligase, E5, chalcone synthase (naringenin-chalcone synthase), E6, chalcone isomerase, E7, Flavonoid 3'-hydroxylase, E8, flavonone 3-hydroxylase, E9, dihydroflavanol 4-reductase, E10, anthocyanidin synthase (leucoanthocyanidin dioxygenase), E11, anthocyanidin reductase. HSCoA, Coenzyme A. L-Tyr, L-tyrosine, L-Phe, L-phenylalanine.
| Image | Name | Formula | Oligomers |
|---|---|---|---|
 | Catechin, C, (+)-Catechin | C15H14O6 | Procyanidins |
 | Epicatechin, EC, (–)-Epicatechin (cis) | C15H14O6 | Procyanidins |
 | Epigallocatechin, EGC | C15H14O7 | Prodelphinidins |
 | Epicatechin gallate, ECG | C22H18O10 | |
 | Epigallocatechin gallate, EGCG, (–)-Epigallocatechin gallate | C22H18O11 | |
 | Epiafzelechin | C15H14O5 | |
 | Fisetinidol | C15H14O5 | |
 | Guibourtinidol | C15H14O4 | Proguibourtinidins |
 | Mesquitol | C15H14O6 | |
 | Robinetinidol | C15H14O6 | Prorobinetinidins |
Flavan-3-ols are abundant in teas derived from the tea plant Camellia sinensis , as well as in some cocoas (made from the seeds of Theobroma cacao ), although the content is affected considerably by processing, especially in chocolate. [8] [9] Flavan-3-ols are also present in the human diet in fruits, in particular pome fruits, berries, vegetables, and wine. [10] Their content in food is variable and affected by various factors, such as cultivar, processing, and preparation. [11]
The bioavailability of flavan-3-ols depends on the food matrix, type of compound and their stereochemical configuration. [12] While monomeric flavan-3-ols are readily taken up, oligomeric forms are not absorbed. [12] [13] Most data for human metabolism of flavan-3-ols are available for monomeric compounds, especially epiatechin. These compounds are taken up and metabolized upon uptake in the jejunum, [14] mainly by O-methylation and glucuronidation, [15] and then further metabolized by the liver. The colonic microbiome has also an important role in the metabolism of flavan-3-ols and they are catabolized to smaller compounds such as 5-(3′/4′-dihydroxyphenyl)-γ-valerolactones and hippuric acid. [16] [17] Only flavan-3-ols with an intact (epi)catechin moiety can be metabolized into 5-(3′/4′-dihydroxyphenyl)-γ-valerolactones (image in Gallery). [18]
As catechins in green tea extract can be hepatotoxic, Health Canada and EFSA have advised for caution, [19] recommending intake should not exceed 800 mg per day. [20]
Research has shown that flavan-3-ols may affect vascular function, blood pressure, and blood lipids, with only minor effects demonstrated, as of 2019. [21] [22] In 2015, the European Commission approved a health claim for cocoa solids containing 200 mg of flavanols, stating that such intake "may contribute to maintenance of vascular elasticity and normal blood flow". [23] [24] As of 2022, food-based evidence indicates that intake of 400–600 mg per day of flavan-3-ols could have a small positive effect on cardiovascular biomarkers. [25]
Gallic acid (also known as 3,4,5-trihydroxybenzoic acid) is a trihydroxybenzoic acid with the formula C6H2(OH)3CO2H. It is classified as a phenolic acid. It is found in gallnuts, sumac, witch hazel, tea leaves, oak bark, and other plants. It is a white solid, although samples are typically brown owing to partial oxidation. Salts and esters of gallic acid are termed "gallates".
Flavonoids are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans.
Polyphenols are a large family of naturally occurring phenols. They are abundant in plants and structurally diverse. Polyphenols include flavonoids, tannic acid, and ellagitannin, some of which have been used historically as dyes and for tanning garments.
Phytochemicals are chemical compounds produced by plants, generally to help them resist fungi, bacteria and plant virus infections, and also consumption by insects and other animals. The name comes from Greek φυτόν (phyton) 'plant'. Some phytochemicals have been used as poisons and others as traditional medicine.
Catechin is a flavan-3-ol, a type of secondary metabolite providing antioxidant roles in plants. It belongs to the subgroup of polyphenols called flavonoids.
Proanthocyanidins are a class of polyphenols found in many plants, such as cranberry, blueberry, and grape seeds. Chemically, they are oligomeric flavonoids. Many are oligomers of catechin and epicatechin and their gallic acid esters. More complex polyphenols, having the same polymeric building block, form the group of tannins.
Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is the ester of epigallocatechin and gallic acid, and is a type of catechin.
Gallocatechol or gallocatechin (GC) is a flavan-3-ol, a type of chemical compound including catechin, with the gallate residue being in an isomeric trans position.
The phenolic content in wine refers to the phenolic compounds—natural phenol and polyphenols—in wine, which include a large group of several hundred chemical compounds that affect the taste, color and mouthfeel of wine. These compounds include phenolic acids, stilbenoids, flavonols, dihydroflavonols, anthocyanins, flavanol monomers (catechins) and flavanol polymers (proanthocyanidins). This large group of natural phenols can be broadly separated into two categories, flavonoids and non-flavonoids. Flavonoids include the anthocyanins and tannins which contribute to the color and mouthfeel of the wine. The non-flavonoids include the stilbenoids such as resveratrol and phenolic acids such as benzoic, caffeic and cinnamic acids.
Prodelphinidin is a name for the polymeric tannins composed of gallocatechin. It yields delphinidin during depolymerisation under oxidative conditions.
Procyanidin C2 is a B type proanthocyanidin trimer, a type of condensed tannin.
A type proanthocyanidins are a specific type of proanthocyanidins, which are a class of flavonoid. Proanthocyanidins fall under a wide range of names in the nutritional and scientific vernacular, including oligomeric proanthocyanidins, flavonoids, polyphenols, condensed tannins, and OPCs. Proanthocyanidins were first popularized by French scientist Jacques Masquelier.
Epicatechin gallate (ECG) is a flavan-3-ol, a type of flavonoid, present in green tea. It is also reported in buckwheat and in grape.
Procyanidin C1 (PCC1) is a B type proanthocyanidin. It is an epicatechin trimer found in grape, unripe apples, and cinnamon.
Condensed tannins are polymers formed by the condensation of flavans. They do not contain sugar residues.
The phenolic content in tea refers to the phenols and polyphenols, natural plant compounds which are found in tea. These chemical compounds affect the flavor and mouthfeel of tea. Polyphenols in tea include catechins, theaflavins, tannins, and flavonoids.
Catechin-7-O-glucoside is a flavan-3-ol glycoside formed from catechin.
Dark chocolate is a form of chocolate containing only cocoa solids, cocoa butter and sugar. Dark chocolate without added sweetener is known as bitter chocolate or unsweetened chocolate. As with the other two main types of chocolate, dark chocolate is used for chocolate bars or as a coating in confectionery.
Helmut Sies is a German physician, biochemist and university professor. He was the first to demonstrate the existence of hydrogen peroxide as a normal attribute of aerobic life in 1970, and he introduced the concept of Oxidative stress in 1985. He also worked on the biological strategies of antioxidant defense and the biochemistry of nutritional antioxidants.
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