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352
Pharmaceutical Chemistry of Natural Products
the chief constituents of the essential oils are the terpenoids having carbon atoms up to C
15
(i.e.
mono and sesquiterpenoids) and their oxygenated derivatives such as alcohols, aldehydes and
ketones. Higher terpenoids, such as diterpenoids and triterpenoids, are found in gums and resins
of plants. Some of the important essential oils with their terpenoid constituents are given in
Table 7.1.
ISOLATION OF TERPENOIDS
As the terpenoids have wide occurrence, there is no general method for their isolation. The
isolation of mono and sesquiterpenoids is carried out in two steps as follows:
1. Isolation of essential oils from the plants.
2. Separation of the individual terpenoids from the essential oils.
Isolation of Essential Oils from the Plants
Four methods have been developed for the isolation of essential oils: (1) expression, (2) steam
distillation, (3) extraction by means of volatile solvents and (4) adsorption in purifi ed fats
(enfl eurage).
1. Expression method: The plant material is processed and crushed; the juice is then screened to
remove the large particles. Using high-speed centrifugal machine, the juice is then centrifuged,
when nearly half of the essential oil is extracted. The other half of the oil is generally not
extracted, which is used for the isolation of inferior quality of oil by distillation.
Application: By this method, lemon, citrus and grass oils are extracted. This method is of
historical importance and not used nowadays.
2. Steam distillation method: The plant material is macerated and then steam distilled when the
essential oils go into distillate. The oils are extracted using a solvent such as light petroleum.
Other distillation methods used are water distillation, water and steam distillation. This is one
of the most widely used method but the disadvantages of using this method are as follows:
Some essential oils may be decomposed during distillation.
Some of the constituents of the essential oils (esters) are cleaved into different products.
Application: By this method, turpentine oil, cinnamon oil, clove oil and peppermint oil are
extracted.
3. Extraction by means of volatile solvents: Some essential oils may be decomposed during distillation.
In these cases, the plant material is directly treated with light petrol at 50°C, and the solvent
is removed by distillation under reduced pressure. The oil obtained by this method is very
pure but the cost of operation is more.
4. Enfl eurage method: The fat taken in glass plates is warmed to about 50°C, then its surface
is covered with petals (part of the fl ower) and is kept as such for several days. With ethyl
alcohol, the petals are then removed and the fat is digested. The essential oils present in fat
are dissolved in ethyl alcohol. The fat which may also dissolve during digestion is removed
by cooling to about 20°C. The extract in ethyl alcohol having essential oils is distilled under
Terpenoids
353
reduced pressure to remove the solvent. Recently, the activated coconut charcoal is used in
place of fat due to the greater stability and more surface as compared to fat.
Application: By this method, turpentine rose oil is extracted in perfume industry.
Separation of Terpenoids from Essential Oils
The essential oils obtained in the fi rst step generally contain a number of terpenoids belonging
to mono and sesquiterpenoid groups. Chemical and physical methods have been used for the
isolation of the individual terpenoids.
Chemical methods
1. Whenever terpenoid hydrocarbons are treated with nitrosyl chloride in CHCl
3
(Tilden’s
reagent), crystalline adducts are obtained. The adducts were separated and decomposed into
their corresponding hydrocarbons.
2. The terpenoid alcohols were separated by treating them with phthalic anhydride to form
diesters as the primary alcohols react readily. Secondary alcohols react less readily and tertiary
alcohols do not react at all.
CO
O
CO
2 ROH
⫹
COOR
COOR
KOH
COOH
COOH
2 ROH
⫹
Phthalic acid
Diesters
Phthalic acid
Alcohol
The diesters after extracting with NaHCO
3
are decomposed by alkali into the parent terpenoid
alcohol.
Physical methods
Physical methods used for the separation of terpenoids are as follows:
1. Fractional distillation
2. Chromatography
However, aldehydes and ketones are separated by treating them with phenylhydrazine,
hydroxylamine, 2,4-dinitro phenylhydrazine, etc.
CLASSIFICATION OF TERPENOIDS
One isoprene unit consists of fi ve carbon atoms. Terpenoids are designated by the general molecular
formula (C
5
H
8
)
n
, where the value of ‘n’ is used as the basis for classifi cation of terpenoids. Different
classes of terpenoids are listed in Table 7.2.
354
Pharmaceutical Chemistry of Natural Products
Table 7.2 Classifi cation of terpenoids
Class of terpenoids Number (n) of isoprene (C
5
H
8
) units Molecular formula
Hemiterpene or isoprene 1 C
5
H
8
Monoterpenes or terpenes 2 C
10
H
16
Sesquiterpenes 3 C
15
H
24
Diterpenes 4 C
20
H
32
Triterpenes 6 C
30
H
48
Tetraterpenes or carotenoids 8 C
40
H
64
Polyterpenes or rubber N (C
5
H
8
)
n
In addition to the hydrocarbons, each class consists of certain oxygenated derivatives such as
alcohols, aldehydes and ketones. Further, each class of terpenoid is classifi ed based on the number
of rings present in the molecule as described in the following section.
Monoterpenoids
Monoterpenoids consist of two isoprene units, containing 10 carbon in their structure and is
further classifi ed as follows:
l. Acyclic monoterpenoids: It contains the open-chain carbon skeleton of the following type:
Examples of this type are shown below.
Nerol Linalool
Ocimene
Myrcene
CHO CH OH
2
CHO CH OH
2
Citral Geraniol Citronellal Citronellol
OH
OH
Terpenoids
355
2. Monocyclic monoterpenoids: Monocyclic monoterpenoids are further classifi ed into three
important classes on the basis of the nature of carbon skeleton. p-Menthane (1-methyl-
4-isopropylcyclohexane), m-menthane (1-methyl-3-isopropylcyclohexane) and 1,1,3-
trimethylcyclohexane derivatives.
p-Menthane m-Menthane 1,1,3-Trimethylcyclohexane
Some of the examples are shown below:
OH
OH
␣-Terpineol Menthol Menthone Carvone
Limonene
1,8-Cineole
Piperitone
-Phellandrene
O
O
O
O
3. Bicyclic monoterpenoids: The bicyclic monoterpenoid can be divided into three classes according
to the size of the second ring. The fi rst ring is a six-membered ring in each class.
Class I: Bicyclic monoterpenoids containing (6 + 3)-membered ring system.
Thujane type
Carane type
356
Pharmaceutical Chemistry of Natural Products
Examples of thujane type are mentioned below:
O
OH
( )-Thujone⫺ Thujyl alcohol
Examples of carane type are mentioned below:
O
Car-3-ene Car-2-ene Carone
1
2
3
4
5
6
Class II: Bicyclic monoterpenoids containing (6 + 4)-membered ring system called pinane
type.
Pinane type ring structure
Examples of this type of terpenoids are shown below:
OH
O
OH
␣-pinene -pinene
Verbenol Verbenone
Pinocarveol
Class III: Bicyclic monoterpenoids containing (6 + 5)-membered ring system. The fi ve different
types of rings existing in this class are shown below:
Terpenoids
357
Norbornane
(Isocamphane)
Bornane
Norbornane
(Fenchane)
Norbornane
(Isobornylane)
Norbornane
Examples of this type of terpenoids are shown below:
Camphor
O
Camphene
Borneol
OH
Isoborneol
OH
Fenchone
O
Sesquiterpenoids
They consist of three isoprene units, containing 15 carbons in their structure and are further
classifi ed as follows:
1. Acyclic sesquiterpenoids
Farnesol Nerolidol
OH
CH OH
2
2. Monocyclic sesquiterpenoids: Four different basic skeletons exist in this type. These, along with
the examples, are shown below:
(a) Bisabolane type
-Bisabolene
Zingiberene
:
358
Pharmaceutical Chemistry of Natural Products
(b) Elemane type
COOH
OH
O
OH
Elemol
Abscisin II (plant hormone)
:
(c) Humulane type
Humulene
:
(d) Germacrane type
O
O
O
Germacrone
Aristolactone
:
3. Bicyclic sesquiterpenoids: Three different basic skeletons exist in this type. These, along with the
examples, are shown below:
(a) Cadinane type
␣-Cadinol ␦-Cadinol
OH
HO
:
(b) Eudesmane type
b) Eudesmane type
-Eudesmol
Santonin
O
O
OH
:
Terpenoids
359
(c) Perhydroazulene type
Guaiacol
:
OH
4. Tricyclic sesquiterpenoids: Two different basic skeletons exist in this type. These, along with the
examples, are shown below.
(a) Cedrene type (e.g. cedrene and cedrol)
Cedrene
OH
Cedrol
(b) Longifolene type (e.g. longifolene)
Longifolene
Diterpenoids
Diterpenoids are compounds containing C
20
in their structure. They are subdivided as follows:
1. Acyclic (e.g. phytol)
CH OH
2
2. Monocyclic (e.g. vitamin A
1
and vitamin A
2
)
CH CH C⭈ CH CH⭈⫽CH C CH CH OH⭈
2
CH
3
CH
3
Vitamin A (Retinol)
1
360
Pharmaceutical Chemistry of Natural Products
CH CH C⭈ CH CH⭈⫽CH C CH CH OH⭈
2
CH
3
CH
3
Vitamin A (3,4-Dehydroretinol)
2
3. Bicyclic: Compounds containing two rings in their structure.
4. Tricyclic (e.g. abietic acid)
HOOC
H
H
Triterpenoids
Triterpenoids are compounds containing 30 carbons in their structure. They may be aliphatic,
tetracyclic or pentacyclic. An example for aliphatic triterpenoid is squalene.
Squalene
Example of tetracyclic triterpenoids are lanosterol and euphol.
OH
OH
Lanosterol Euphol
Terpenoids
361
Tetraterpenoids
Tetraterpenoids are compounds containing 40 carbons in their structure. The important compounds
belonging to this class include carotenoids.
b-Carotene
Luteolin
HO
OH
Polyterpenoids
Polyterpenoids consist of many isoprene units. Rubber is a common example of polyterpenoid.
Pharmaceutically important polyterpenoid is gutta-percha, which consists of many isoprene units
but lesser than rubber. In gutta-percha, these units are trans to each other, whereas in rubber, they
are cis to each other.
ISOPRENE RULE AND SPECIAL ISOPRENE RULE
All the terpenoids are derived from one monomeric structural unit called isoprene and hence they
are sometimes also referred as isoprenoids. The common structural features of terpenoids are the
empirical formula (C
5
H
8
) and their thermal decomposition product yield isoprene as one of the
products.
The isoprene rule states that the skeleton structures of all naturally occurring terpenoids are
built up of isoprene units.
The isoprene rule is further confi rmed by the following facts:
1. Isoprene may be dimerized to afford terpenoid called dipentene.
2C H
58
CH
10 16
D
Isoprene Dipentene
2. Isoprene can be polymerized to yield rubber like product (a polyterpenoid).
nCH
58
(C H
58
)
n
Isoprene Rubber
Polymerization