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Course No.: CHM-3132/542

Course Title: Organic Chemistry-II

Class: BS-III/M.Sc.-I

Course In-charges: Dr. Najma Rasool/Dr. Farzana

Naz 2
INTERACTIVE CLASS WILL BE

ON ZOOM APP

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FLAVONOIDS

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 i-DIETARY SOURCES
 Flavonoids (specifically flavanoids such as the
catechins) are "the most common group of
polyphenolic compounds in the human diet and are
found ubiquitously in plants".
 Flavonols, the original bioflavonoids such as
quercetin, are also found ubiquitously, but in lesser
quantities.
 The widespread distribution of flavonoids, their
variety and their relatively low toxicity compared to
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other active plant compounds (for instance alkaloids)
mean that many animals, including humans, ingest
significant quantities in their diet.
 Foods with a high flavonoid content include parsley,
onions, blueberries and other berries, black tea, green
tea and oolong tea, bananas, all citrus fruits, Ginkgo
biloba, red wine, sea-buckthorns, buckwheat, and
dark chocolate with a cocoa content of 70% or
greater.
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 OOLONG TEA
Oolong ( /ˈuːlʊŋ, -lɒŋ/; simplified Chinese: 乌龙 ; traditional
Chinese: 烏龍 (wūlóng, "dark dragon")) is a traditional semi-
oxidized Chinese tea (Camellia sinensis) produced through a
process including withering the plant under strong sun and
oxidation before curling and twisting.

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Parsley: Parsley, both fresh and dried, contains
flavones.
Blueberries: Blueberries are a dietary source of
anthocyanidins.
Black tea: Black tea is a rich source of dietary flavan-
3-ols.

Blueberries are a source of dietary Parsley is a source of flavones

anthocyanidins 9
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Citrus: The citrus flavonoids include hesperidin (a glycoside
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of the flavanone hesperetin), quercitrin, rutin (two glycosides

of the flavonol quercetin), and the flavone tangeritin. The
flavonoids are much less concentrated in the pulp than in the
peels (for example, 165 vs. 1156 mg/100g in pulp vs. peel of
satsuma mandarin, and 164 vs 804 mg/100g in pulp vs. peel
of clementine).

A variety of flavonoids are found in

citrus fruits, including grapefruit
Hesperidin Quercitrin

Rutin Tangeritin 12
Wine
Cocoa: Flavonoids exist naturally in cocoa, but because
they can be bitter, they are often removed from
chocolate, even dark chocolate. Although flavonoids are
present in milk chocolate, milk may interfere with their
absorption; however this conclusion has been
questioned.
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Peanut: Peanut (red) skin contains significant
polyphenol content, including flavonoids.

Unit: mg/100g 14
 CONTENT OF THE LECTURE

i-Dietary sources

ii-Dietary intake

iii-Research

iv-Synthesis
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v-Test for detection

vi-Quantification

vii-Semi-synthetic alterations

viii-References

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 OBJECTIVES / LEARNING GOALS

At the end of lecture, In Sha ALLAH we will be able

to understand the chemistry of phenolics and

flavanoids.

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 RELATION TO THE LAST LECTURE

In previous lecture we discussed flavanoids.

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 ii-DIETARY INTAKE
 Food composition data for flavonoids were provided by the
United States Department of Agriculture (USDA) database
on flavonoids.
 In the United States National Health and Nutrition
Examination Survey (NHANES) survey, mean flavonoid
intake was 190 mg/d in adults, with flavan-3-ols as the
main contributor.
 In the European Union, based on data from European Food
Safety Authority (EFSA), mean flavonoid intake was 140
mg/d, although there were considerable differences
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among individual countries.
The main type of flavonoids consumed in the EU and
USA were flavan-3-ols (80% for USA adults), mainly
from tea or cocoa in chocolate, while intake of other
flavonoids was considerably lower.

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 iii-RESEARCH
 Neither the United States Food and Drug
Administration (FDA) nor the European Food Safety
Authority (EFSA) has approved any health claim for
flavonoids or approved any flavonoids as
prescription drugs.
 The U.S. FDA has warned numerous dietary
supplement companies about illegal advertising and
misleading health claims.
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 Metabolism and excretion
 Flavonoids are poorly absorbed in the human body (less
than 5%), then are quickly metabolized into smaller
fragments with unknown properties, and rapidly excreted.
 Flavonoids have negligible antioxidant activity in the
body, and the increase in antioxidant capacity of blood
seen after consumption of flavonoid-rich foods is not
caused directly by flavonoids, but by production of uric 22
acid resulting from flavonoid depolymerization and
excretion.
 Microbial metabolism is a major contributor to the
overall metabolism of dietary flavonoids.
 The effect of habitual flavonoid intake on the
human gut microbiome is unknown.
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 Gut microbiota

Gut microbiome, gut flora, or microbiome are the

microorganisms including bacteria, archaea and fungi

that live in the digestive tracts of humans and other

animals including insects.

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 Inflammation
 Inflammation has been implicated as a possible origin of
numerous local and systemic diseases, such as cancer,
cardiovascular disorders, diabetes mellitus, and celiac
disease.
 There is no clinical evidence that dietary flavonoids affect
any of these diseases.
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 Coeliac disease

Coeliac disease or celiac disease is a long-term

autoimmune disorder that primarily affects the small

intestine

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 Cancer
 Clinical studies investigating the relationship
between flavonoid consumption and cancer
prevention/development are conflicting for most
types of cancer, probably because most human
studies have weak designs, such as a small sample
size.
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 There is little evidence to indicate that dietary
flavonoids affect human cancer risk in general, but
observational studies and clinical trials on hormone-
dependent cancers (breast and prostate) have shown
benefits.
 A recent review has suggested that dietary intake of
flavonoids is associated with a reduced risk of
different types of cancer, including gastric, breast,
prostate, and colorectal (large intestine) cancer.
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 Cardiovascular diseases
 Although no significant association has been found
between flavan-3-ol intake and cardiovascular disease
mortality, clinical trials have shown improved endothelial
function and reduced blood pressure (with a few studies
showing inconsistent results).
 Reviews of cohort studies in 2013 found that the studies
had too many limitations to determine a possible
relationship between increased flavonoid intake and
decreased risk of cardiovascular disease, although a trend
for an inverse relationship existed.
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 Endothelial dysfunction
In vascular diseases, endothelial dysfunction is a
systemic pathological state of the endothelium.
Endothelium
Endothelium is a single layer of squamous endothelial
cells that line the interior surface of blood vessels, and
lymphatic vessels. 30
 IN VITRO
 Laboratory studies on isolated cells or cell cultures in vitro
indicate that flavonoids may selectively inhibit kinases,
but in vivo results could differ because of low
bioavailability.
 Bioavailability is a subcategory of absorption and is the
fraction (%) of an administered drug that reaches the
systemic circulation. 31
 KINASES
A kinase is an enzyme that catalyzes the transfer of
phosphate groups from high-energy, phosphate-donating
molecules to specific substrates. This process is known
as phosphorylation, where the high-energy ATP
molecule donates a phosphate group to the substrate
molecule.
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 iv-SYNTHESIS
COLOR SPECTRUM
 Flavonoid synthesis in plants is induced by light color
spectrums at both high and low energy radiations. Low
energy radiations are accepted by phytochrome, while high
energy radiations are accepted by carotenoids, flavins,
cryptochromes in addition to phytochromes.
 The photomorphogenic process of phytochrome-mediated
flavonoid biosynthesis has been observed in Amaranthus,
barley, maize, Sorghum and turnip. Red light promotes
flavonoid synthesis. 33
 PHYTOCHROMES
Phytochromes are a class of photoreceptor in plants,
bacteria and fungi used to detect light.

CAROTENOIDS

Carotenoids (/kəˈrɒtɪnɔɪd/), also called tetraterpenoids,

are yellow, orange, and red organic pigments that are
produced by plants and algae, as well as several
bacteria, and fungi. 34
 FLAVIN
Flavin (from Latin flavus, "yellow") is the common name for a group
of organic compounds based on pteridine, formed by the tricyclic
heterocycle isoalloxazine. The biochemical source is the vitamin
riboflavin.

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 CRYPTOCHROME
Cryptochromes (from the Greek κρυπτός χρώμα,
"hidden colour") are a class of flavoproteins found in
plants and animals that are sensitive to blue light.

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 PHOTOMORPHOGENESIS
Photomorphogenesis is light-mediated development,
where plant growth patterns respond to the light
spectrum.
This is a completely separate process from
photosynthesis where light is used as a source of
energy.
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 AVAILABILITY THROUGH
MICROORGANISMS
 Several recent research articles have demonstrated the efficient
production of flavonoid molecules from genetically engineered
microorganisms and the project SynBio4Flav aims to provide a
cost-effective alternative to current flavonoid production
breaking down their complex biosynthetic pathways into
standardized specific parts, which can be transferred to
engineered microorganisms within Synthetic Microbial Consortia
to promote flavonoid assembly through distributed catalysis.
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 v-TESTS FOR DETECTION
Shinoda test
Four pieces of magnesium filings are added to the ethanolic
extract followed by few drops of concentrated hydrochloric
acid. A pink or red colour indicates the presence of flavonoid.
Colours varying from orange to red indicated flavones, red to
crimson indicated flavonoids, crimson to magenta indicated
flavonones. 39
 SODIUM HYDROXIDE TEST
About 5 mg of the compound is dissolved in water,
warmed, and filtered. 10% aqueous sodium hydroxide
is added to 2 ml of this solution. This produces a yellow
coloration. A change in color from yellow to colorless
on addition of dilute hydrochloric acid is an indication
for the presence of flavonoids. 40
 p-DIMETHYLAMINOCINNAMALDEHYDE
TEST

A colorimetric assay based upon the reaction of A-rings

with the chromogen p-dimethylaminocinnamaldehyde

(DMACA) has been developed for flavanoids in beer

that can be compared with the vanillin procedure.

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 COLORIMETRIC ASSAYS

Colorimetric assays are reactions that lead to a change

of color due to an enzymatic or chemical interaction

between spotted reagents and the analyte.

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 vi-QUANTIFICATION
Lamaison and Carnet have designed a test for the
determination of the total flavonoid content of a sample
(AlCI3 method). After proper mixing of the sample and the
reagent, the mixture is incubated for ten minutes at ambient
temperature and the absorbance of the solution is read at 440
nm. Flavonoid content is expressed in mg/g of quercetin.
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 vii-SEMI-SYNTHETIC ALTERATIONS

Immobilized Candida antarctica lipase can be used to

catalyze the regioselective acylation of flavonoids.

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 viii-REFERENCES

1-Dewick, P. M. Medicinal Natural Product, A

Biosynthatic approach, Willey John & Sons, 3rd edition,
2009.
2- Ø. M. Andersen, K. R. Markham 'Flavonoids:
Chemistry, Biochemistry and Applications. Boca Raton,
FL: CRC Press, Taylor & Francis, 2006. 45
3-I. L. Finar, “Organic Chemistry,” Volume-2:

Stereochemistry and the Chemistry of Natural Products,

5th edition, Pearson Education, 2008.

4-V. Alagarsamy, “Pharmaceutical Chemistry of Natural

Products” Elsevier, 2012. 46

5-Jin Dai, Russell J. Mumper, “Plant Phenolics:

Extraction, Analysis and Their Antioxidant and

Anticancer Properties ,” Molecules, 2010, 15, 7313-

7352.

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