TERPENOIDS

Oktavia Rahayu A, S.Farm., M.Biomed

Departemen Farmasi Bahan Alam, PSSF FKUB 2018
PRE-TEST
1. Gambarkan 1 unit isoprene!
2. Berikan masing-masing satu contoh tanaman yang mengandung
senyawa terpenoid dari kelas:
- Monoterpenoid
- Seskuiterpenoid
- Diterpenoid
- Triterpenoid
Mahasiswa mampu …
• memahami definisi dan jalur biosintesis
senyawa terpenoid CAPAIAN
• memahami klasifikasi senyawa
golongan terpenoid PEMBELAJARAN
• menjelaskan sifat fisika kimia senyawa
trepenoid dan kaitannya dengan
metode isolasi serta pemilihan fase
gerak untuk KLT.
• menjelaskan senyawa –senyawa
terpenoid yang memiliki efek
farmakologi dan jenis tanamannya
(misal : asiaticoside, andrografolide,
artemisinin, ginkgolide, iridoid)
INTRODUCTION OF
TERPENOIDS
 TERPENES AND TERPENOIDS
Terpenes - class of >20,000 compounds containing carbon atoms in multiples of five
Terpenoids - oxygen-containing terpenes (alcohols, ketones, aldehydes)

The name "terpene" is derived from the word "turpentine“

Terpenes and terpenoids are the primary constituents of the essential oils of many types of
plants and flowers

rose oil (zencefil) (kereviz)

5
 The basic molecular formulae of terpenes 
multiples (C5H8)n known as isoprene (2-methyl-
1,3-butadiene) units This is called the isoprene
rule or the C5 rule.
Compounds containing carbon atoms in multiples
of 5 suggest a C5 building block - isoprene units
linked in a “head-to-tail” fashion

2-methyl-1,3-butadiene

“Head” - branched end of isoprene

“Tail” - unbranched end of isoprene
6
Finding the isoprene building block - cyclic compounds

Finding the isoprene building block - sesquiterpenes (C15)

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 Finding the isoprene building block - triterpenes (C30) -

Squalene has a natural and vital part in the synthesis of all plant and animal sterols, including
cholesterol, steroid hormones, and vitamin D in the human body

Finding the isoprene building block - tetraterpenes (C40)

Lycopene's eleven conjugated double bonds give it its deep red color and are responsible for its antioxidant activity.
Lycopene is responsible for the red color in tomatoes and watermelon

-carotene is the compound that causes carrots and apricots to be orange 8

OVERVIEW OF PHARMACOGNOSY

DRUG CONTAINING MONOTERPENOID

Gentiana lutea Plantago sp. Valeriana officinalis

Gentian Root Plantago Leaves Valerian Root

iridoid Seco iridoid

DRUG CONTAINING SESQUITERPENOID

Tanacetum parthenium Artemisia annua

Feverfew Flower Artemisia Herb

Sesquiterpene lactone Sesquiterpene lactone
DRUG CONTAINING DITERPENOID

Ginkgo biloba Andrographis paniculata

Ginkgo Leaves Andrographis Leaves
DRUG CONTAINING TRITERPENOID 
SKELETON FOR STEROID

Picrasma excelsa Centella asiatica

Quassia Wood Centella Herb

BIOSYNTHESIS OF
TERPENOIDS
BIOSYNTHESIS PATHWAYS IN PLANTS
Remember?

PP=pyrophosphate
(1) Terpenes
from Acid: The
Mevalonate
Pathway
 Aldol cond

SN2 Enzimle hid.

Tioesterden alkole
 Isopentenyl pyrophosphate is only one of the necessary reagents for the biosynthesis of terpenes…
dimethylallyl pyrophosphate, a C5 isomer, is also necessary:

Add. of H+ elimination of a proton

RULE - isopentenyl pyrophosphate and dimethylallyl pyrophosphate are the C5 building blocks for the
biosynthesis of terpenes

Elimination of a proton from a carbocation intermediate generates a double bond (E1 reaction)
Geranyl pyrophosphate - C10 building block for many biological monoterpenes
Geranyl pyrophospate ester hid ile geraniol verir. 24
(2) Terpenes from Sugar: The Deoxyxylulose
Phosphate Pathway

(13) products pyruvate; (14) glyceraldehyde 3-phosphate

CLASSIFICATION OF
TERPENOIDS
Terpenoids
contain isoprene
unit (C5)
 Classification of terpenoids
Carbon Classification Example
atoms
5 Hemiterpenes Prenol, isovaleric acid
10 Monoterpenes geraniol, limonene, terpineol
15 Sesquiterpenes humulene, farnesenes, farnesol
20 Diterpenes cafestol, kahweol, cembrene,
taxadiene, retinol, retinal, phytol
25 Sesterterpenes Geranylfarnesol
30 Triterpenes Squalene
40 Tetraterpenes lycopene, alpha-, beta- and
gamma- carotenes
Polyterpenes
C10 Monoterpenoids
 Monoterpenoids
• Major class of compounds in essential oils
• Skeleton 2 x isoprene precursors, joined head to tail
Tail Modification e.g.
Cyclisation
Head

• Occuring widely in higher plant but tend to accumulate in certain

members of plant: Labiatae (e.g. Rosemary, Mentha, thyme),
Pinaceae (e.g Pinus spp) , Rutaceae (e.g Citrus spp) and
Umbelliferae (e.g Cumin)  These plants used for commercial
production of essential oil
Linking of isoprene units to form monoterpenoid

Further modification e.g

Oxidation, cyclisation
Functions
 In plants: attracting polinator (e.g. insect) to flowers, protection from
herbivores and microbial infection
 In insect: defence and pheromonal secretion
pheromones  chemical produced by organism that affect the
behaviour of other organisms
e.g 1) Honeybee queen release certain pheromone and passed amongst
bee workers and coordinate all activities.
2) Certain female insect release pheromone to attract male insect
during mating.
 Classification of Monoterpenoids
acyclic

Based on monocyclic
structure: bicyclic
irregular
Monoterpenoids
unsaturated hydrocarbon  C=C
Based on alcohol  OH
functional
group aldehyde  COH
ketone  C=O
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35
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Acyclic monoterpenes

Bicyclic monoterpenes

Monocyclic monoterpenes
 Example of Monoterpenoids
Classification?
which one is the isoprene units?

Camphor A. annua
• Found in: Camphor tree (Cinnamomum camphora, Lauraceae),
artemisia spp (Compositae)
• Irritant and toxic to human
• commercially used as moth repellant
• also used as preservative in pharmaceutical and cosmetics

C. camphora
 Example of Monoterpenoids

Carvone
• Main constituent in the essential oil of
spearmint (Mentha spicata)
• Carminative and antiseptic
• Used in manufacture of liqueurs,
confectionary, perfumery and soap.
Citronellal
• Main constituent of Java oil (Cymbopogon nardus
= Andropogon nardus, sereh ); Eucalyptus spp.
• Antiseptic, sedative, soap, perfume, and insect
repellant (minyak tawon).
 Example of Monoterpenoids

Methofuran Methol Methone

• Occurs in the essential oils of Mentha spp.

• Menthol used as analgesic,
• Menthone and methol used as antiseptic, carminative also as flavouring
agent in pharmaceutical, confectionary
 Monoterpenoid containing cyclopentane ring fused
Iridoids with six-memberred oxygen heterocycle

Bitter tasting compound

Usually occur as glycoside, with glucose attached

to OH group

The aglycones are highly unstable and decomposed

Plant containing iridoid glycoside often turn into dark or

blue colour during drying
 Derived from iridoid, catalysed by cytochrome P-450
Iridoids and involves opening of the pentacyclic ring.

Play important role in the biosynthesis of

terpene alkaloid together with amino acids, e.g
tryptophan

Plants containing iridoid and seco-iridoid have

important role in folk medicine: tonics, anti
Seco-iridoids inflammation, antimicrobial agent, laxative,
diuretic and sedative.

Large concentration of iridoid glycoside in the

presence of acid can be toxic
Example of iridoids

Loganin Deoxyloganin

• Found in: fruit of Strychnos nux-vomica and other

Strychnos spp (Loganiaceae); also found in
Catharanthus roseus (= Vinca rosea, Apocynaceae)
• Used as laxative and bitter tonic.

Strychnos nux-vomica also contain alkaloid strychnin

which is deadly poison to human at 30-120 mg dose.
Example of iridoids

Valtratum

• Found in the roots of Valeriana spp

(Valerianaceae).
• Together with other valepotriates
compound showed sedative effect
Example Seco-iridoids

Secologanin

• Derived from opening of the cyclopentane ring of loganin

•Found in: Catharanthus roseus (= Vinca rosea, Apocynaceae)
as minor constituent; probably widespread in plant containing
indole alkaloid (why???)
• Precursor of several indole alkaloid
Example Seco-iridoids

Yellow gentian

Gentiopicrin

• Found in: roots of Gentiana lutea and

other plant in the family Gentianaceae
• Bitter taste
• Antimalarial activity
Willow gentian
Gentiana asclepiadea
Characteristics of Monoterpenoids
Have strong smell

Colourless

Oily

Boiling point 140-180°C

Some are crystalline e.g Camphor

Iridoid and seco-iridoids are bitter tasting

Can be separated and identified by GC combine with MS, NMR

Example of 1H NMR of Iridoid

Adoxocidic acid from

Fagrea blumei
C15 Sesquiterpenoids
 Sesquiterpenoids
• Derived from 3 isoprene units  C15
• Constituent of essential oil together with monoterpenoids.
• Function in plant: phytoalexins or antifeedant produced as response
to fungal attack or herbivores, e.g rishitin  antifungal
• Occurrence:
- higher plant (Labiatae, Myrtaceae, Pinaceae, and Rutaceae)
- Marine animal, e.g sponge
- Insect as pheromone
Characteristics of Sesquiterpenoids
Colourless

Oily
Boiling point normally higher than monoterpenoid
(160-200°C)

Some have pleasant odour

Some are bitter tasting

Optical isomerization (-) and (+) forms  relation to (S)-Abscisic acid
bioactivity, e.g abscisic acid only the (+) cis isomer cis isomer
shows hormonal activity to control stomatal closure
Classification of Diterpenoids
No real classification for sesquiterpenoids

Acyclic

Based on structural
Cyclic
modification addition of functional group:
lactone, ketone, alcohol,
Bicyclic carboxylic acid etc

Sesquiterpenoid lactone, Sesquiterpenoid quinone

One structure can have several functional groups

There is no fixed shape
 Monocyclic sesquiterpenes
Acyclic sesquiterpenes

Bicyclic sesquiterpenes
 Example of Sesquiterpenoids

Which are the three

isoprene units?

Carotol from Daucus carota

Which are the three

isoprene units?

Cinnamodial from Cinnamosma fragrans

African medicinal plant
 More Example of Sesquiterpenoids
Fumagillin
• Isolated from the fungus Aspergillus fumigatus
• Antibiotic and antiparasitic

Lubimin (1)
• Found in the tuber of potato (Solanum tuberosum,
Solanaceae) and in the fruit of eggplant (Solanum
melongena, Solanaceae) infected by patogenic fungus.
(2) • Phytoalexin  antifungal
(1)

Solavetivone (2)
• Found in the tuber of potato (Solanum tuberosum, Solanaceae) and in tobacco
(Nicotiana tabacum, Solanaceae) infected by patogenic fungus and virus, respectively.
• Phytoalexin  antifungal

Sesquiterpenoid Lactones
• Sesquiterpenoids with lactone
functionality  C10 with lactone
• Existed as mixtures with other related
compounds, e.g other terpenoid
• Structural modification: 1) addition of
various functional groups: OH, OCH3,
glycoside, halogen. 2) dimerisation
• Biologically active, many of them
have antitumour properties, however
highly toxic  prevent further
development as medicine.
Sesquiterpenoid Quinones
• Sesquiterpenoids with quinone
functionality  C10 with quinone
• Structural modification: 1) addition of
various functional groups: OH, OCH3.
• Biologically active, many of them
showed antimicrobial.
• Mostly found from marine samples,
rarely from plants
Classification of Sesquiterpenoid Lactones
According to the ring structures
 Eudesmanolides  two fused six-
membered rings
Alantholactone
Parthenolide
 Germacranolides  ten-membered
ring

 Guaianolides  five-membered ring

fused to seven membered ring,
methyl substituted at C-4

 Pseudoguaianolides  the same Achillin

as guaianolide but methyl substituted
at C-5
Ambrosin
 Characteristic and Distribution of
Sesquiterpenoid Lactones
• Lipid soluble
• Crystalline
• Can be isolated from dried plant material
Characteristics
with DCM
• Separation on silica gel column
• Bitter tasting compound

• Characteristic constituent in compositae (e.g

Artemisia spp)  concentrated in the aerial
Distribution
parts (Leaves, flowers) about 5% of dry
weight.
Sesquiterpenoid Lactones in Compositae/Asteraceae
Source Compounds Bioactivity/Usage
Achillea millefolia Achillin Plant growth inhibitor, converted
into chamazulene anti-
inflammatory
Inula helenium Alantolactone Antibiotic
Artemisia annua Artemisinin Anti malaria
Artemisia absinthum Absinthin Anthelmintic, flavouring agent in
alcoholic beverages
Cnicus benedictus Cnicin Antibacterial, antitumor and
antifeedant
Arnica montana Helenalin Anti-inflammatory, very
poisonous to humans
Tanacetum parthenium Parthenolide For treatment of migraine
 Example of Sesquiterpenoid Quinones

Zonarol Spongiaquinone
• Isolated from alga Dictyopteris zonarioides • Isolated from sponge Stelospongia conulata
• Showed antifungal activity • Showed antifungal and antibacterial activity
C20 Diterpenoids
Diterpenoids
Skeleton  C20, 4x isoprene units

The most bitter tasting compounds compared to other terpenoids

Some are very toxic to humans

Appearance: usually crystalline solid

Optically active  due to stereogenic center

Rarely found in glycosidic form

Can be isolated from plant using non polar solvent e.g Hexane, Chloroform etc.
Classification of Diterpenoids
Acyclic

Cyclic

Based on structural
Bicyclic
modification

Tricyclic some have additional

functional group such as
carboxylic acid, lactone
Tetracyclic
 Example of Diterpenoids
Andrographolide Gibberellin A3

• Isolated from • Isolated from the fungus

Andrographis Gibberella fujikuroi
paniculata (sambiloto, (Fusarium moniliforme)
Acanthaceae) • Plant growth hormon
• Bioactivity: anticancer, • Commercially used for
hepatoprotective, brewing beer, breaking seed
immunomodulator. dormancy, and produce
seedles grapes.
 Ginkgo biloba

Bioactivity: cardiovascular health

C30 Triterpenoids
 Triterpenoids
 Skeleton: C30, 6 x isoprene units
 The precursor of triterpenoid is squalene, first isolated from shark liver.
 Structure of squalene is related to plant triterpenoid/steroid
irreguler
Classification of Triterpenoids
(1) Triterpenoid saponin

(2) Steroidal saponin

(3) Cardenolides and Bufadienolides

(4) Cucurbitacin

(5) Nortriterpenoid

(6) Phytosterols

Other triterpenoid
(1) Triterpenoid saponin
• Triterpenoid attached to a glycoside
• Combination of hydrophilic and hydrophobic  ability to lower
surface tension, soap like
• Like soap, this compound produce foams in water
• Widely distributed in flowering plants.
• Bioactvities: antifungal, antihypertensive, anti-inflammatory, sedative
etc
 Example of Triterpenoid saponin

Glycyrrhizin Ginsenoside Rf
• Found in the root and rhizome of • Found in the root of Panax ginseng
Glycyrrhiza glabra • Tumor inhibitory activity
• Very sweet taste
• Recently found to have Anti –HIV activity
(2) Steroid saponin
• Steroid is not true triterpenoid because the skeleton
cannot be broken down into isoprene unit
• C27 not C30, but biosynthetic origin is related
• Steroid saponin : steroid + glycoside

The steroid ring systems

R group at C17 determines
the base name of an
individual steroid

Oxidised at several positions

+ glycoside
sterane
Cyclopentano perhydro phenanthrene nucleus
Example of Steroid saponin

Diosgenin
Dioscin • Obtained from acid hydrolisis of many
• Found in Dioscorea spp different saponins e.g Dioscin
(Dioscoreacea), Costus spp • Used in partial synthesis of hormone
(Zingiberaceae) having a steroid structure, e.g progesterone
Saponin and sapogenin
• Sapogenin is acid hydrolisis product of saponin (loss of Glycosidic linkage)
• Different pollarity
 Identification of triterpenoid/steroid saponins

Generally bitter taste but some are very sweet, e.g glycyrrhizin from
Glycyrrhiza glabra (akar manis)
the presence of foam in extract indicated saponin
Acid hydrolysis to give free triterpenoid
Colour reactions:
Liebermann-Burchard H2SO4 several colours
Antimony chloride  red to blue colours
Perchloric acid  special for steroid and triterpenoid
NMR
(3) Cardenolides and Bufadienolides
 C23 and C24 steroids, derived from triterpenoids
 Both cardenolide and bufadienolide occur as O-glycoside
The cardenolides are structurally closely
Bufadienolides are usually C24 steroids related to the bufadienolides, but possess
and their glycosides. They possess a a five-membered lactone (butenolide)
chromophoric six-membered lactone (α- ring at C-17β. This imparts a characteristic
pyrone) ring at C-17β UV absorption at ca. 220 nm in methanol.
Glycosylation commonly occur at C-3, less
at C-1, C-2 or C-11
Example of Cardenolides and
Bufadienolides

Digitalin

Found in the seeds of Digitalis

purpurea (Scrophulariaceae)
• Toxic to vertebrate
• Used as cardiotonic
Digitoxin
(4) Cucurbitacin
A group of oxygenated tetracyclic triterpene

First characterised in cucumber, squash (Cucurbitaceae)

This compound also found in other source

Concentrated in the roots and seeds of the plants

Occur as free and glycosidic forms

So far has been found

cucurbitacins A- S Bitter taste compound

Beetles feeding on cucumber, absorb, store this metabolite

and later use it as chemical defence.
(5) Nortriterpenoids
Derived from tetracyclic triterpenoid  oxidation and
degradation  form nortriterpenoid which has less than 30
carbons

Divided into 2 groups:

• Limonoid  loss of 4 carbons in the side chain of
tetracyclic triterpenoid  C26
• Quassinoid  loss of the side chain and other carbon
atoms  C20 or C19

Both limonoid and quassinoid are bitter tasting compounds

Limonoids can be found abundantly in the family Rutaceae (Citrus

spp), while quassinoids in the family Simaroubaceae (Quassia
spp)
 Example of Limonoid and Quassinoid
Limonoid Limonin
• Found in Citrus spp (Navel and Valencia oranges)
• Occur during ripening, caused delayed bitterness in citrus

Azadirachtin A
• Found in Azadirachta indica (mimba, Meliaceae)
• Potent insect anti feedant  commercially used as
insectiside in the USA

Quassinoid

Brusatol
• Found in Brucea sumatrana (Simaroubaceae)
• Anti protozoal (Plasmodium falciparum)
(6) Phytosterol
Sterol structurally derived from skeleton cyclopentana perhydro phenanthrene

Found in animal product and plant tissue

Distinctive in animal : Cholesterol

Distinctive in plant: sitosterol, stigmasterol and campesterol

In fungi : Ergosterol

Phytosterol (Plant sterol) structurally can be differentiate from animal sterol due to
additional methyl or ethyl substituent in the side chain

Phytosterol  derived from squalene

Phytosterol e.g sitosterol play role in plant cell growth  component of plant cell
membrane
 Example of Phytosterol
Skeleton:
Cyclopentana perhydro penanthrene
OH substituent at C-3

Cholesterol
•Occur in the pollen of date palm (Phoenix dactylifera) and in red algae
•Common sterol in animal
•Used in pharmaceutical as emulsifying agent

β-Sitosterol
•Found in most higher plant
•Component of plant cell membrane
Ergosterol
• Found in yeast and fungi e.g Saccharomyces cerevisiae
and Gibberella fujikuroi
• When irradiated with UV light forms vitamin D2
(ergocalciferol)
C40 Tetraterpenoids
Tetraterpenoids
Skeleton  C40, 8 x isoprene units

Lipid-soluble pigments, also known as carotenoids

 carotenoids give colour to animals through
dietary intake, such as starfish, lobster etc

In plants have 2 functions:

1) For photosynthesis together with chlorophyl
2) Colouring agents in flowers and fruits ; yellow
colour in flowers ; orange or red in fruits

Usage  food colour, provitamin A activity

Example of Tetraterpenoids

β-Carotene
Found in: all green leaves of plants, also in bacteria, fungi, algae roots, e.g Daucus
carota, Ipomoea batatas
fruit, e.g paprika yellow and orange flowers
Provitamin A, colouring agents for food, e.g Margarine

Lycopene
Found in: ripe fruits, e.g tomato, citrus spp
Carrot, also in the seeds of ripe
 Latihan
Identifikasi unit isoprene dari masing2 senyawa berikut!
Lycopene

Ginsenoside Rf
Parthenolide

Secologanin

rha-glc-glc

Loganin
H Asiaticoside Andrographolide
Tugas
Carilah masing-masing satu senyawa terpenoid (monoterpenoid,
sesquiterpenoid, diterpenoid, triterpenoid, tetraterpenoid) pada
tanaman kemudian identifikasi masing-masing unit isoprene yang
terdapat pada tanaman tersebut

Tulis tangan  foto  upload ke google classroom, deadline tanggal 19

April 2018
Contoh Soal
KASUS
Seorang peneliti menemukan bahwa suatu senyawa golongan terpenoid dapat menghambat fungsi efluks P-
glikoprotein secara signifikan sehingga dapat dipertimbangkan sebagai chemo-sensitizer dan terapi ajuvan pada
pengobatan kanker multi drug resistance (MDR).

1. Disebut apakah senyawa tersebut?

2. Pernyataan mana yang benar mengenai senyawa tersebut?
A. β-sitosterol A. Titik didih 140-180°C
B. β-glucan B. Berwarna kuning hingga orange
C. β-pinene C. Timbul busa jika dikocok
D. Rasanya pahit
D. β-lactam
E. Berupa minyak
E. β-carotene
THANK YOU