Flavonoid 1-1 PDF

Flavonoids These are group of polyphenolic compounds found in plants. Of all secondary metabolites, they are most abundant in nature and are widely distributed across families of higher plants like Leguminosae, Compositae, Rutaceae, Polygonaceae, and Umbelliferae. They are kown to be useful...

Flavonoids These are group of polyphenolic compounds found in plants. Of all secondary metabolites, they are most abundant in nature and are widely distributed across families of higher plants like Leguminosae, Compositae, Rutaceae, Polygonaceae, and Umbelliferae. They are kown to be useful chemotaxonomic markers. The word flavonoid is derived from the latin word flavus meaning yellow due to the characteristic yellow color they produce. As secondary metabolites, they play important roles in defense mechanism of plants and are commonly found in plant parts like seeds, vegetables, fruits, flowers. They are the color pigments in plants and attract pollinating insects. They play significant roles in plant growth by activating or inhibiting enzymes. Flavonoids occur in both free and combined states (as glycosides). Structure/Chemistry of Flavonoids phenylpropanoid They are formed from 3 acetate units and a phenyl propanoid. Their structure is represented as C6-C3-C6 system. They possess 15 carbon atoms containing two benzyl (ring A and B) rings that are linked together by a linear three carbon chain (ring C).In most cases, B ring is attached to position 2 of C ring, but it can also bind in position 3 or 4. The B-ring is formed from shikimic acid pathway via phenylalanine. Ring A is formed from head-to-tail condensation of three acetate units which are derived from malonyl-CoA to 4-coumaroyl by the catalytic action of chalcone synthase. The three carbon atom group from phenyl propanoid ring (C6C3) may undergo rearrangement to form a five-membered or six-membered heterocyclic ring incorporated into the full structure through an oxygen group between the two phenyl groups to form a five-membered heterocyclic ring (Furan) as in aurones or a six-membered heterocyclic ring (Pyran) to give Flavonoids which are most abundant in nature. aurone flavonoid. Flavonoid glycosides Being glycosides, they contain the glycone and aglycone part. The aglycone moiety is made of a benzyl ring fused with a pyran ring (six membered heterocyclic ring) attached to another phenyl ring through the carbon atom at positon 2. The glycone moiety may be attached at position3 and 7 and can be a D-glucose, L-rhamnose, galactose or arabinose. The phenolic hydroxyl groups are point of attachment for the sugar moiety. The hydroxyl groups OH groups are found in positions 5 and 7 in ring A, while in ring B, 3i, 4i, and 5i commonly carrying -OH or alkoxyl groups. Most flavonoid glycosides are O-glycosides, but a number of C-glycosides are also known. They dissolve in alkali giving yellow solutions Classification of Flavonoids Flavonoids can be classified into different classes depending on the carbon of the C ring on which B ring is attached, and the degree of unsaturation and oxidation of the C ring. Flavonoids in which B ring is linked in position 3 of the ring C are called isoflavones those in which B ring is linked in position 4, neoflavonoids, while those in which the B ring is linked in position 2 can be further divided into several subgroups on the basis of the structural features of the C ring. These subgroups are: flavones, flavonols, flavanones, flavanonols, flavanols or catechins and anthocyanins. Finally, flavonoids with open C ring are called chalcones.  1. Flavones (2-phenyl-chromen-4-one): They have a double bond between positions 2 and 3 and a ketone in position 4 of the C ring Examples are: Apigenein, Luteolin, Tangeritin, Diosmetin Flavones 5 7 3i 4i Apigenin OH OH H OH Luteolin OH OH OH OH Tangeritin O-Me O-Me H O-Me Diosmetin OH OH OH O-Me Basic structure of flavones 2. Flavonol (3-hydroxy-2-phenyl-chromen-4-one). Flavonols have a hydroxyl group in position 3 of the C ring, which may also be glycosylated. Again, like flavones, flavonols are very diverse in methylation and hydroxylation patterns as well, and, considering the different glycosylation patterns, they are perhaps the most common and largest subgroup of flavonoids in fruits and vegetables. For example, quercetin is present in many plant foods. Examples are Kaempferol, Rutin,Myricetin, Quercetin, Quercetrin, Fisetin. Structure of flavonol. Flavonol 3 7 3i 5i Kaempferol OH OH H H Myricetin OH OH OH OH Quercetin OH OH OH H Quercetrin O-Rh OH OH H Fisetin OH O-Me OH H 3. Flavanone (2, 3-dihydro-2-phenylchromen-4-one). Flavanones, also called dihydroflavones, have the C ring saturated; therefore, unlike flavones, the double bond between positions 2 and 3 is saturated and this is the only  structural difference between the two subgroups of Flavonoids that is Flavones and Flavans. Examples are Hesperitin, Hesperidin, Naringenin. Flavanone structure Flavanone 5 7 3i 4i Hesperitin OH OH OH O-Me Hesperidin OH O-Rutinose OH O-Me Nanrigenin OH OH H OH 4. Flavanonol (3-hydroxy-2,3-dihydro-2-phenylchromen-4-one) Examples are Taxifolin,Silymarin Structure of Flavanonol 5. Flavanols (also called Catechins or Flavan-3-ols): They have an OH group always attached to C3 and a disappearance of the ketone group at position C4 but the C ring still remains saturated. Examples are Catechin (β-OH trans - configuration) Epicatechin(α-OH cis-configuration) Each of these configurations have two stereoisomers: +(-) epicatechin, -(-) epicatechin, +(-) catechin, -(-) catechin. Flavan-4-ol Flavan-3,4-diol.  Another important feature of flavanols, particularly of catechin and epicatechin, is the ability to form polymers, called proanthocyanidins or condensed tannins. The name “proanthocyanidins” is due to the fact that an acid-catalyzed cleavage produces anthocyanidins. 6. Isoflavones(3-Phenyl-chromen-4-one): The ring b is attached at C3 instead of C2. They have structural similarities to estrogens, such as estradiol, and for this reason they are also called phytoestrogens. Examples are; Genistein, Daidzin Structure of Isoflavones Isoflavone 3 5 7 4i Genistein - OH OH OH Daidzin H O-Glu OH 7. Neoflavonoids (4-phenyl coumarins) the ring B is attached at C4. Exaples include: Dalbergiones, Dalbergiquinois, neoflavone, 4-arylchromanes. 8. Anthocyanidins (2-Phenyl-chromenylium):  Chemically, anthocyanidins are flavylium cations and are generally present as chloride salts. They are sugar free pigments of plants and the only group of flavonoids that gives plants colors. Anthocyanins are glycosides of anthocyanidins. Sugar units are bound mostly to position 3 of the C ring and they are often conjugated with phenolic acids, such as ferulic acid. Examples are Cyanidin, Delphenidin. Structure of anthocyanidin Chalcones Chalcones and dihydrochalcones are flavonoids with open structure; they are classified as flavonoids because they have similar synthetic pathways. Common examples include: Crotaramin, Crotmadine, Sappanchalcone etc. Biosynthesis Flavonoids are synthesized by the phenylpropanoid metabolic pathway in which the amino acid phenylalanine is used to produce the phenyl propanoid ring (C6-C3 unit). The B-ring is formed from shikimic acid pathway via phenylalanine. Ring A is formed from head-to-tail condensation of three acetate units which are derived from malonyl-CoA to 4-coumaroyl by the catalytic action of chalcone synthase. The phenyl propanoid ring combines with malonyl-CoA to yield the true backbone of flavonoids, chalcones. Chalcone is an important intermediate product in the synthesis of flavonoids. Conjugate ring-closure of chalcones results in the familiar form of flavonoids, the three-ringed structure of a flavone. The metabolic pathway continues through a series of enzymatic modifications to yield flavanones → dihydroflavonols → anthocyanins. Along this pathway, many products can be formed, including the flavonols, flavan-3-ols, proanthocyanidins (tannins) and a host of other various polyphenolics. Dihydroflavanol Flavanonol Flavanone Flavanone Chalconene Test for detection Sodium hydroxide test: to aqueous extract of plant material, add 10% aqeous NaOH. This gives a yellow color. A change in color from yellow to colorless on addition of HCl confirms the presence of flavonoid. Shinoda test: to the ethanolic extract, add few pieces of magnesium fillings (ribbons) + few drops of HCl. A pink or red color indicates the presence of Flavonoids. Orange – red color indicates flavones, red – pink indicates Flavonoids, pink - -magenta indicates flavonones. Ammonia solution test: to aqueous extract, add ammonia solution. The color turns yellow. Upon addition of H2SO4, the yellow color disappears. Lead acetate test: to extract, add few drops of lead acetate solution. Formation of a yellow solution indicates the presence of Flavonoids. Pharmaceutical significance of Flavonoids 1. They exhibit potent antioxidant effect. They protect the body from oxidative stress by mopping up free radicals and reactive oxygen species ROS. They react with these highly unstable compounds to form stable compounds thereby protecting the body from several oxidative-induced disorders. The flavones and catechins are the most powerful Flavonoids with antioxidant activity. 2. Anti-inflammatory effect. Flavonoids inhibits cyclo-oxygenase pathway (inflammatory response cascade) by reducing arachidonic acid production. Quercetin exhibit potent anti-inflammatory response. 3. Anti-ulcer effects. They act as gastro-protective agents by increasing gastric mucus secretion. Quercetin has been reported to inhibit growth of H.pylori in in-vitro studies 4. Anti-artherosclerosis. Flavonoids reduce levels of Low density lipoprotein(LDL) and inflammatory progression in artery walls. They protect against coronary heart disease 5. As an adjunct in management of neurodegenerative disorders. 6. Many Flavonoids exhibit hepato-protective effects like silymarin, apigenin, quercetin and naringenin. 7. Others : anti-allergy, detoxicant, anti-microbial, weight loss Common examples and sources Citrus aurantium (Orange peel): hesperidin Garcinia cambogia: bioflavonoids Glycine max (Soybeans): isoflavones Glycyyrhiza glabra(Liquorice): bioflavonoids Vaccinium macrocarpon (Cranberry):Quercetin Fagopyrum esculetum (Buck wheat): Rutin