This document summarizes flavonoids, lignanans, and quassinoids. It describes their structures, including that flavonoids are based on the flavan nucleus and have a chromene ring condensed with a phenyl ring. Lignanans have a C-C bond between two phenylpropane units. Quassinoids are bitter constituents from Simaroubaceae that are triterpene degradation products highly oxygenated with lactone rings. It also outlines their biosynthesis, noting flavonoids originate from the shikimic acid pathway and lignanans form through enzymatic dimerization. Their pharmacological actions are also listed.

1. CHEMISTRY AND BIOSYNTHESIS OF
FLAVONOIDS, LIGNANANS AND QUASSINOIDS
PREPARED BY
MR.ARAVIND R
MPHARM
SJCOPS, Kerala

2. FLAVONOIDS
 Flavonoids are low molecular weight polyphenolic substances based on the
‘flavan’ nucleus. It occurs in free form as well as in glycosidic form.
 There are example for Phenyl propanoid derivative- C6-C3 derivative.
 Figure below shows the generic structure of flavonoid and the numbering
system used to distinguish the carbon positions around the molecule.

3. Flavonoid structure
 The three rings – A and B is chromene ( benzene fused with a
pyran), and C (phenyl)
 Six-member ring condensed with the benzene ring is either a
pyran or its dihydro derivative.
 When glycosides of flavonoids are formed, the glycosidic
linkage is normally located in positions 3 or 7 and the
carbohydrate can be L-rhamnose, D-glucose, glucorhamnose,
galactose or arabinose eg. Rutin –O- Glucoside, Kaempferol-
0-glucoside

8. FLAVANONE
2,3 dihydro 2-phenyl chromene 4-one
STRUCTURE Examples
 Naringin
 Hesperitin
 Hesperidin
 Naringenin
 Butin

13. PHARMACOLOGICAL ACTION
 ANTIOXIDANT
 ANTI-INFLAMMATORY
 ANTIULCER
 ANTI-RHEUMATIC
 HEPATOPROTECTIVE Eg.Silymarin
 ANTIATHEROSCLEROSIS
 ANTICANCER

16. BIOSYNTHESIS
 Via Shikhimic acid pathway (Phenyl propanoid pathway)
 Precursor i.e. three molecules of acetic acid and phenyl
propane moiety.
 Interaction of different pathways: Glycolysis(Phosphoenol
pyruvate), Pentose Phosphate pathway(to get Erythrose 4
phosphate) and Shikhimic acid pathway(aromatic
biosynthesis)
 the general phenylpropanoid metabolism that produces
activated cinnamic acid derivatives (4-coumaroyl- CoA)
and also the plant structural component lignin and finally
the diverse specific flavonoid pathways.

17. Biosynthesis
 A cinnamic acid derivative (phenyl propane), synthesized
from shikimic acid, acts as the starting compound in a
polyketide synthesis, in which an additional three acetate
residues are incorporated into the structure and this is
followed by ring closure.
 Through subsequent hydroxylation’s and reductions, plants
are then able to biosynthesized different classes of
flavonoids like flavonols, flavones, flavanones, catechins
(or flavanols), anthocyanidins, iso-flavones, dihydro-
flavonols, and chalcones.

20. LIGNANANS
 Lignans are a subgroup of non-flavonoid polyphenols.
 Do not occur in free form, but occur in glycosidic form
 They are widely distributed in the plant kingdom, being present in more
than 55 plant families, where they act as antioxidants and defense
molecules against pathogenic fungi and bacteria.
 Podophyllotoxin , obtained from plants of the genus Podophyllum
peltatum and P.hexandrum (Berberidaceae family); it is a mitotic toxin
whose derivatives have been used as chemotherapeutic agents;
 arctigenin and tracheologin(Antiviral), obtained from tropical climbing
plants;
 Linseed (Flaxseed) contains Secoisolariciresinol, lariciresinol,
pinoresinol and matairesinol.

21. Chemical structure
 Two phenylpropane units linked by a C-C bond between
the central atoms of the respective side chains (position 8
or β), also called β-β’ bond. 3-3′, 8-4′, or 8-3′ bonds are
observed less frequently; in these cases the dimers are
called neolignans.
 Hence, their chemical structure is referred to as (C6-C3)2,
and they are included in the phenylpropanoid group, as
well as their precursors: the hydroxycinnamic acids

26. ❑ In fact, most of the plant lignans exists as (+)- or (-)-
enantiomers, whose relative amounts can vary from
species to species, but also in different organs on the
same plant, depending on the type of reactions
involved.
❑ The dimerization can occur through enzymatic
reactions involving laccases. These enzymes catalyze
the formation of radicals that, dimerizing, form a
racemic mixture.

27. Quassinoids
 Bitter constituents of the Simaroubaceae and the characteristic secondary
metabolites of this family.
 The generic term quassinoids arises from quassin, the name of the first
structurally identified member of this class isolated from species Quassia
amara.
 The Simaroubaceae family includes 32 genera and more than 170 species of
trees .

28. Chemistry
 These consist of triterpene degradation products, derived from the euphol/ tirucalol
series, highly oxygenated and structurally complex.
 Regarding the basic structure, they can be structurally classified into five groups: C-
18 (1), C-19 (2), C-20 (3), C-22 (4) and C-25 (5a, 5b), though some do not fit any
given configuration, such as (+)-polyandrol, eurylactones A and B, ailanquassins A and
B, 6-dehydroxylongilactone etc.
 Most of the isolated quassinoids have a twenty carbon skeleton
 The quassinoids are heavily oxygenated lactones (-lactone in the quassolidane
skeleton and lauricol and -lactone in the cedrolidane actane skeletons, and -
lactone and -lactone in the other skeletons), with variable of groups hydroxyl,
hydroxyl esterified, carbonyl, methoxyl and carbomethoxyl.

30. Quassin

31. Quassin synthesised from S-carvone

32. Biogenesis from Euphol