1. Terpenoids Introduction Therapeutic Properties Classification Biosynthesis Details of Cucurbitacin 2. Coumarins Introduction Details of Umbelliferon

1. Biosynthetic
Pathways for
Terpenoids
and
Coumarins
Presented by Chhavi
M. Pharm 1st Year
Delhi Pharmaceutical Sciences and
Research University

2. Jens
Martensson
Contents
A. Terpenoids
• Introduction
• Therapeutic Properties
• Classification
• Biosynthesis
• Details of Cucurbitacin
B. Coumarins
• Introduction
• Details of Umbelliferon
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3. Jens
Martensson
Terpenoids
Introduction
• Represent the largest class of natural products with a
diverse array of structures and functions
• Terpenoids are secondary metabolites mostly produced
by plants and some by bacteria or yeast
• With around 64, 000 known compounds, are considered
the largest and most diverse class of natural products
• Widely used in the flavors and fragrance industries, in
addition to being a source of biofuels
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Martensson
Therapeutic Properties
• Antimicrobial
• Antifungal
• Antiviral
• Antiparasitic
• Antihyperglycemic
• Antiallergenic
• Anti-inflammatory
• Antispasmodic
• Immunomodulatory
• Chemotherapeutic properties
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Examples of Some Terpenoids

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Also be used as
• Natural insecticides
• Protective substances
in storing agriculture products
Terpenoids recently emerge as strong
players in the biofuel market
Among the terpenoids with established
medical applications are
• Antimalarial - Artemisinin
• Anticancer - Taxol
Continued…

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Martensson
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Classification of Terpenoids
Terpenoids are usually classified according to the number and structural organization of
the five carbon isoprene units involved in their synthesis as
Structure of an Isoprene unit

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• Despite the enormous structural differences between terpenoids, they are all derived from the same C5
skeleton of isoprene
• The terpenoidal backbone is synthesized from the two precursors:
a. Isopentenyl pyrophosphate (IPP)
b. Dimethylallyl pyrophosphate (DMAPP)
through a different number of repeats, rearrangement and cyclization reactions
• Two distinct biosynthetic pathways for the formation of these universal precursors have been reported,
1. The Mevalonate (MVA) Pathway
2. The 2C-methyl-D-erythritol-4-phosphate (MEP) Pathway
also known as the 1-deoxy-D-xylulose- 5-phosphate (DXP) Pathway
Biosynthesis of Terpenoids

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Biosynthesis Pathways
• Present in eukaryotes (all mammals,
the cytosol and mitochondria of
plants, fungi), archaea, and some
eubacteria
• Comprises seven enzymatic reactions
to convert the precursor acetyl-CoA
to IPP and DMAPP
M E P
• Occur in eubacteria, algae,
cyanobacteria, and the chloroplasts of
plants
• Converts the starting materials, pyruvate
and glyceraldehyde-3-phosphate, to IPP
and DMAPP through eight enzymatic
reactions
M V A

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Martensson
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• The linear prenyl diphosphates such as geranyl pyrophosphate (GPP), farnesyl pyrophosphate (FPP),
geranylgeranyl pyrophosphate (GGPP), and farnesyl geranyl pyrophosphate (FGPP) are synthesized from the
two basic building blocks, IPP and DMAPP where a group of enzymes called prenyltransferases repeatedly
add the active isoprene unit (IPP) to DMAPP or a prenyl diphosphate in consecutive head-to-tail
condensations leading to the production of a range of molecules with fixed lengths and stereochemistry
• Geranyl pyrophosphate synthase (GPPS) and farnesyl pyrophosphate synthase (FPPS) catalyze the
condensation of IPP and DMAPP to produce GPP (C10) and FPP (C15)
• Geranylgeranyl pyrophosphate synthase (GGPPS) and farnesyl geranyl pyrophosphate synthase (FGPPS) are
responsible for formation of GGPP (C20) and FGPP (C25)
• The precursors GPP, FPP, GGPP and FGPP, are cyclized and/or rearranged by different terpene synthase
enzymes to produce the different classes of terpenoids
Continued…

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Continued…

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Martensson
CHARACTERIZATION
Terpenoids are
• colorless liquid
• Soluble in organic solvent
• Insoluble in water
• Volatile in nature.
• B.P. is150-180ºC
• Unsaturated compound
• Contain isoprene unit in chemical
structure.
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Martensson
Cucurbitacin
Introduction
• Bitter-tasting principle that can be
isolated from members of the family
Cucurbitaceae, such as cucumber
(Cucumis sativus) and melon (Cucumis
melo L.)
• In particular, cucurbitacin and
momordicine, which have an intensely
bitter taste, are contained abundantly in
Momordica charantia
• There are more than 18 kinds of
cucurbitacin, and among them
cucurbitacin B is a typical component
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Martensson
DIFFERENT SOURCE OF CUCURBITACIN
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Momordica
Melon
Pumpkin
Cucumber

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USES
• Anti-inflammatory
• Anti-tumor
• Anti-diabetic
• Anti-artherosclerotic
• Anti-oxidant activity
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CHARACTERIZATION
• Taste – bitter
• Color - yellowish
• Mol. Formula - C32H44O8
• Molecular weight - 556.696 g/mol
• Chemical structure of cucurbitacin

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Biosynthesis

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ISOLATION
Cucurbitacin containing plant
material
Pressing
Liquid containing cucurbitacin
Extracted with non polar solvent like chloroform to
remove the waxes, pigments, fatty acid terpenes
Separated liquid is then extracted with moderately polar
solvent like water
Separation of cucurbitacin
Collection of cucurbitacin

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Martensson
PURIFICATION
• It can be done by using flash
chromatography, column
chromatography, paper chromatography
TLC
• Solvent system used TLC are
i. Toluene : ethyl acetate (40 : 60)
ii. Chloroform : ethanol (95: 5)
• Structure identify by following method
- By UV spectroscopy
- By IR spectroscopy
- By Mass spectroscopy
- By NMR spectroscopy
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Martensson
• Plant-derived natural products
• Colorless crystalline substance in its standard state
• Fragrant organic chemical compound in the benzopyrone chemical class, although it
may also be seen as a subclass of lactones
• Exhibit various biological activities such as Antibacterial, Antioxidant, Anti-
inflammatory, Rodenticidal, Termiticidal etc.
• Based on their structural and biosynthetic properties, plant coumarins are
categorized as follows:
1. simple coumarins
2. Furanocoumarins
3. Pyranocoumarins
4. Coumarins with modifications in the pyrone ring
Coumarins
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Martensson
Continued…
• It has a sweet odor, and has been use in
perfumes
• Coumarin is classify in various class such as
simple coumarin, furocoumarin,
pyrancoumarin etc.
• It is naturally occur in different family such as
umbelliferae, rutaceae, leguminoseae etc.
• It is used in the pharmaceutical industry as a
precursor reagent in the synthesis of a number
of synthetic anticoagulant
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Martensson
Umbelliferone
• Umbelliferone, also known as 7 hydroxycoumarin, hydrangine, skimmetine, and beta-
umbelliferone, is a natural product of the coumarin family. it is benzopyron in nature
• Source: Umbelliferone occurs in many familiar plants from the Apiaceae (Umbelliferae)
family such as carrot, coriander and garden angelica, as well as in plants from other
families
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Biosynthesis
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1. Umbelliferone From malic acid

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1. The phenylpropanoid biosynthetic path way for coumarins synthesis.
2. The key steps in the biosynthesis of umbelliferone coumarin are the cinnamic acid synthesis or para
and ortho hydroxylations, trans-cis isomerization of the double bond and finally lactonization of
cinnamic acid
3. From trans - cinnamic acid
Continued…

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ISOLATION AND EXTRACTION
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• From Bark Acacia nilotica, Family Mimosaceae
Bark
Powder
Extraction with hexan
(thrice)
24h at room temp.
Residu
e
Hexan
extraxct
Extraction with chloroform
(thrice)
24h at room temp
Residu
e
Chloroform extract
Extraction with ethyl acetate
(thrice)
24h at room temp.
Ethyl acetate
extract
Residue

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Residue
Residue Acetone extract
Extraction with acetone
(thrice)
24h at room temp
Extraction with methanol
(thrice)
24h at room temp.
Residue Methanol
extract
Subjected to column
chromatography
Extraction with water (thrice)
24h at room temp
Residue Water extract
Flow chart of extraction of various extracts Acacia nilotica
in increasing order of solvent polarity.

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Martensson
It can be done by
• HPTLC
• HPLC
• Flash chromatography
• Column chromatography
• Paper chromatography
Structure identify by following method
• UV spectroscopy
• IR spectroscopy
• Mass spectroscopy
• NMR spectroscopy
PURIFICATION
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Martensson
• Color - yellowish-white crystals
• Taste - bitter
• Solubility - slightly soluble in hot water, but have good solubility in ethanol
• Molecular formula - C9H6O3
• Molecular weight - 130g/mol
• Melting point - 224–227ºC
• Molecular structure
CHARACTERIZATION
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Martensson
• The ultraviolet activity of umbelliferone lead to its use as a sunscreen agent
• As an anti bacterial and antifungal activity
• Used in diabetes
• Anti cancer and anti toxicity
• Molluscicdal activities
• Fluorescent probe
• An optical brightener for textiles
USES
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Martensson
References
• AGlimpseintotheBiosynthesisofTerpenoids.pdf
• http://dl.konkur.in/post/Book/MedicalScience/Trease-and-Evans-Pharmacognosy-16th-
Edition-%5Bkonkur.in%5D.pdf
• https://www.researchgate.net/figure/Coumarin-biosynthetic-pathway-in-plants-Simple-
coumarins-coumarin-1-umbelliferone_fig2_268786426
• coumarinandterpenoids-190911161949.pdf
• Evans & Trease, A textbook of Pharmacognosy
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30. Any
questions ?

31. Thank
You