Flavan-3-ol

Flavan-3-ols (sometimes referred to as flavanols) are a subgroup of

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

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]

Biosynthesis of (–)-epicatechin

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,

. HSCoA, Coenzyme A. L-Tyr, L-tyrosine, L-Phe, L-phenylalanine.

Aglycones

Flavan-3-ols

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

Dietary sources

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]

Bioavailability and metabolism

The

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

Research has shown that flavan-3-ols may affect

• 
  Schematic representation of the flavan-3-ol (−)-epicatechin metabolism in humans as a function of time post-oral intake. SREM: structurally related (−)-epicatechin metabolites. 5C-RFM: 5-carbon ring fission metabolites. 3/1C-RFM: 3- and 1-carbon-side chain ring fission metabolites. The structures of the most abundant (−)-epicatechin metabolites present in the systemic circulation and in urine are depicted.^[17]
• 
  Flavan-3-ol precursors of the microbial metabolite 5-(3′/4′-dihydroxyphenyl)-γ-valerolactone (gVL). Only compounds with intact (epi)catechin moiety result in the formation of γVL by the intestinal microbiome. ECG, (−)-epicatechin-3-O-gallate; EGCG,

  Epigallocatechin.^[18]