1 INTRODUCTION OF TERPENOIDS

A plethora of naturally occurring plant products have been found to be related wherein they
are comprised of one or more units of isoprene (C5H8)-a hydrocarbon:

In general, terpenoids, may be defined as natural products whose structures are considered to
be divided into several isoprene units; therefore, these compounds are invariably termed
as isoprenoids. Besides, this particular group of compounds is sometimes collectively referred to
as the terpenes in relatively older texts. Logically, the–oid suffix seems to be more acceptable an
convincing, as it is in the same vein for steroids, alkaloids, flavonoids, etc., However, the-
enesuffix must be solely confined to the unsaturated hydrocarbon belonging to this specific class
of compounds.
It has now been established experimentally that the isoprene units come into being through the
biogenetic means starting from acetate via mevalonic acid. Each such unit essentially consists of
five-carbons having two unsaturated bonds and possesses a branched chain.
The terpenoids usually have a number of such isoprene units joined together in a head to tail
manner, as exemplified below:
Terpenoids are broadly classified on the basis of the number of isoprene units incorporated
into aspecific unsaturated hydrocarbon terpenoid molecule, such as:
(a) Monoterpenoids: These are built up of two isoprene units and have the molecular
formula C10H16;
(b) Sesquiterpenoids: These are composed of three isoprene units and have the molecular
formula C15H24;
(c) Diterpenoids: These are comprised of four isoprene units and have the molecular
formula C20H32;
 (d) Triterpenoids: These contain six isoprene units and have the molecular formula
C30H48; and
(e) Tetraterpenoids These are made up of eight isoprene units and have the molecular (or
Carotenoids): formula C40H64.
Biogenetic Isoprene Rule The very idea and basic concept that terpenoids are essentially
built up of several isoprene units is commonly termed as the biogenetic isoprene rule as could
be observed from the various typical examples cited earlier.
Meroterpenoids It has been observed that a good number of other natural products do exist
which essentially belong to mixed biosynthetic origin and are mostly made up from isoprene as
well as nonisoprenoid entities.

Examples A few typical examples are: ergotamine, quinine, cannabinol and vitamin-E.
More than 20, 000 naturally occurring large variety of terpenoids have been duly isolated and
characterized, and thus constitute a major congregation of such products when compared to any
other individual class of natural products. In fact, the chemical ecology rests heavily and
predominantly on the occurrence of profusely distributed plant terpenoids, and hence, the latter
play a broad-spectrum of highly specific and characteristic roles in the plant kingdom, such as:
insect propellents and antifeedants, phytoalexins, attractants for pollingranes,
pheromones, defensive substances against herbivorous animals, allelochemicals, signal
molecules and above all the plant growth hormones. Terpenoids usually engage in a variety of
probable interactions, forinstance: plant and plant, plant and microorganism, and plant and
animal.
The International Union of Pure and Applied Chemistry (IUPAC) recommends a systematic
mode of nomenclature of terpenoids; however, the names suggested by it are not only lengthy
but also quite cumbersome. Therefore, the old and the trivial names of most terpenoids are used
most frequently even today for naming the relatively common substances: examples:

Trivial Name IUPAC Name

Geraniol 3, 7- Dimethyl-2, 6-octadien-1-ol;

Limonene 1-Methyl-4-(1-methylethynyl)- cyclohexene;
β-Myrecene 7-Methyl-3-methylene-1, 6-octadiene;
Carbon-Skeleton in Terpenoids A comparative study of carbon-skeleton in terpenoids has
revealed that a great majority of monocyclic terpenes essentially possess a para menthane carbon
skeleton; besides, derivatives of cyclopentane and methylated cyclohexanes also exists
invariably.
Generally, two different methods of tackling the structural problems normally encountered
interpenoids are adopted, namely:
(i) Dehydrogenation: Mostly the terpene hydrocarbon, dienes, upon dehydrogenation give
rise top-cymene. Having identified the prevailing carbon-skeleton in it, the exact location of the
double bonds in the existing framework may be established by oxidative degradation to the
corresponding simple aliphatic acids, and
(ii) Oxidation: Tilden was pioneer for the strategic incorporation of nitrosyl chloride (O=N–
Cl) function by the help of a specific reagent (Tilden Reagent) so as to characterize and ensure
the purity of the starting material via formation of definite crystalline derivatives of the
corresponding terpenes under investigation. It has been established by Tilden’s study that the
olefenic linkage reacted specifically with this reagent to yield the
respective nitrosochloride adduct, as shown below:
 In a situation, where the C-atom possesses both nitrosomoiety and a H-atom, the former
undergoes isomerization readily to yield isonitrochloride an oxime. However, in the absence of
this specific characteristic feature the nitrosochloride is fairly stable.
It has been observed that when the substance is monomeric* the corresponding
nitrosochloride provides a distinct blue colouration, which also ascertains the presence of
tetrasubstituted ethylenes.

CLASSIFICATION OF TERPENOIDS
Based on the extensive distribution of terpenoids in the vast plant kingdom they are classified
broadly as follows, namely:
(i) Monoterpenoids
(ii) Sesquiterpenoids
(iii) Diterpenoids
(iv) Triterpenoids
(v) Tetraterpenoids and Carotenoids
(vi) Volatile Oils (or Essential Oils)
(vii) Resins and Resin Combinations
(viii) Oleoresins
(ix) Oleo-Gum-Resins
(x) Balsams
These different classes of naturally occurring substances shall be discussed individually in
the sections that follows:

2.1 Monoterpenoids
In general, monoterpenoids represent a structurally diverse class of compounds may be
categorised into nearly 35 varying structural analogues. However, the most commonly occurring
structural variations are of the following types, namely:
 It has been found that a large number of monoterpenoid derivatives belonging to
these categories invariably occur naturally in the purest optically active form; however,
certain plant species do have both enantiomers, such as: Pinus species contain both
(+)- and (–)-α – pinene.
A few typical examples of monopenoids found in naturally occurring plant species are
described under: camphor, eucalyptol, menthol and thymol.

2.1.1 Camphor
Synonyms Gum camphor; Japan camphor; Formosa camphor. Laurel
camphor.

Biological Source It occurs in all parts of the camphor

tree, Cinnamonum camphora.T. Nees & Ebermeier, belonging to
family Lauraceae.

Geographical Source The word camphora is derived from the

Arabic Kafur, meaning chalk. The camphor tree, which is a huge evergreen
plant, is found to be indigenous to Japan, China and Taiwan. It has also been
naturalized specifically in the Mediterranean region eg; Algeria, Tunsia,
Libya, Egypt, Italy and Greece. Besides it is grown in South Africa, Ceylon,
Brazil, Jamaica, Florida and California. History reveals that Borneo camphor
(from Borneol) arrived in Arabia in the sixth century and in Europe in the
twelth century. Earlier, the worlds 80% supply of natural camphor was
provided by Taiwan (Formosa) alone and the rest 20% by Japan and
Southern China. Soonafter the second World War (1945) the commercial
production of synthetic camphor has more or less catered for the ever
increasing demand of camphor in the world market.
 Preparation It is prepared from the chipped wood by subjecting it to
steam distillation and subsequently collecting the distillate in specifically
designed chambers where camphor will solidify on its miner walls upon
colling and may be collected later on from the bottom of the chamber. The
crude solidified camphor is purified by mixing it with a suitable proportion of
soda lime, sand and charcoal; and subjecting the mass to sublimation at
controlled temperature when pure crystals of camphor would be collected as
a sublimate. It is finally compressed into either small cubes or thin plates,
wrapped and exported.

Camphor from Volatile Oils It may be prepared from volatile oils

by two simple methods, namely:

Methods-I In case, the oil contains a substantially large proportion

of camphor, it may be separated

by deep freezing or sudden chilling; and if the camphor content in oil is

not so much it is mostly fractionated and the camphor containing fraction is
chilled to recover camphor.

Method-II Camphor may be recovered from volatile oils by the instant

production of insoluble complexes with strong mineral acids eg; sulphuric
acid 80% (30N).

Synthetic Camphor (or Borneol Camphor) The camphor is obtained

commercially from α-pinene present in the turpentine oil through several
steps sequentially e.g., treatment with HCl, isomerization, treatment with
KOH and finally oxidation with HNO3 as given below:

Description

Colour : Translucent mass with crystalline fraction

Odour : Characteristic odour

Optical Activity : Natural camphor = Dextro rotatory (+ 41o to 43o)

Synthetic camphor = Racemic mixture;
 Solubility : Soluble in water (1:600)

Chemical Structure Camphor is a bycyclic terpenoid ketone as given

below:

In the presence of platinum black it undergoes hydrogen at ambient

temperature giving rise to isoborneol as the major product and traces
of borneol.

Its prolonged hydrogenation often yields camphene.

2.1.2 Eucalyptol
Synonyms Cineole; Cajeputol.

Biological Source It is obtained from the leaves of Eucalyptyus

globulus Labill, belonging to family Myrtaceae.
 Geographical Source The eucalyptus tree is a native of Australia and
Tasmania. It is largely cultivated in Calfornia, Spain, Portugal and India. In
India it is abundantly found in the Himalayan region, Nilgiri district, Kumaon
Hills and Assam.

Preparation A number of volatile oils from certain Eucalyptus

species invariably contain eucalyptol as high as 30 to 70%. It also occurs
in cajuput oil (40%) and in laurel leaf oil(50%).
However, eucalyptol may be isolated from these oils by adopting one of the
following methods:

Method 1 By subjecting the volatile oil to fractional distillation and

collecting the fractions between 170-180oC to obatin crystals of cineole at –
10oC (m.p. + 1.5oC)

Method-2 Cineole forms addition compounds with halogen acids, e.g.,

C10H18O HCl and C10H18O. HBr; with phosphoric acid as C10H18O.H3PO4 which
also serve as a means of its purification, and

Method 3 Eucalyptol yields an addition product with a 50% (w/v)

alcoholic solution eg; C10H18O. C6H6O2 (mp 82-85oC), from which the former
may be generated.

Note: This method is mostly applicable to such volatile oils that

have a higher cineole content.

Synthetic Method Eucalyptol may be prepared synthetically by the

dehydration ofterpin hydrate as given below:

Description

Colour : Colurless or pale yellow liquid.

Odour : Camphoraceous and aromatic.

 Taste : Pungent and leaves a cold sensation.

Solubility : Water insoluble; soluble in paraffin, fixed oils and ethanol

90%.

Chemical Structure

Eucalyptol is an epoxy or oxido derivative of p-menthane. and is also

known as 1,8-epoxy-pmethane or 1,8-oxido-p-menthane. It is found to be
quite stable and hence may be distilled over metallic sodium safely without
undergoing any change whatsoever. It is not affected by the action of
reducing agents.

Chemical Tests

1. When a drop of eucalyptol is carefully treated with a drop of 5% (w/v)

solution of hydroquinone in alcohol on a slide, it forms either colourless
prisms or rhomboids; but with a 50% (w/v) solution of resorcinol in alcohol
leaf-like crystals are obtained.

2. It forms characteristic addition compounds with HCl, HBr and

H3PO4 with well defined melting points.

Uses

1. It is used internally as a stimulating expectorant to relieve severe

cough and in bronchitis in the form of inhalatious.

2. It is abundantly employed externally as a mild anaesthetic and

antiseptic for the treatment of various inflammatory conditions.
2.1.3 Menthol
Synonyms 1-Menthol; 3-Menthanol; Menthan-3-ol; Peppermint camphor,
Hexahydrothymol.

Biological Sources It is found in the peppermint oil obtained from the

fresh flowering tops of the plants commonly known as Mentha piperita Linn.,
or other allied species ofMentha, belonging to family Labiatae.

Geographical Source Various mentha species are duly cultivated in

various parts of the world. It grows both abundantly and widely in Europe,
while it is cultivated in Japan , Great Britain, Italy,France, United States, CIS
countries, Bulgaria and India.

Preparation It is normally prepared from Japanese Peppermint Oil, from

the flowering tops of Mentha avensis Linne’ var piperascens, by subjecting it
to refrigeration below –22oC whereby the menthol crystallizes out distinctly.
The crystals of menthol are separated by filteration and squeezes between
layers of filter papers to remove the adhering oil and finally purified by
recrystallization.

Synthetic racemic menthol is prepared by the hydrogenation of

either pulegone orthymol as shown below:
 It may also be prepared from pinene.

Description

Colour : Colourless

Odour : Pleasant peppermint like odour

Taste : Characteristic, aromatic and cooling taste

Shape : Hexagonal cyrstals usually needle like, prisms; crystalline

powder; fused masses.

Chemical Structure Menthol has three chiral centres (*), hence it would
give rise to eight (23) optically active isomers and four racemic
forms. Menthol on oxidation gives menthone (a ketone), by the sacrifice of
one chiral centre; therefore, the resulting menthone must exist in four (2 2)
optically active isomers and two recemic forms and all, these have been
actually prepared.
 Special Features following are the special features of menthol, namely:

(a) Dehydrogenation: Menthol first on dehydration yields two isomeric

forms of p-menthane, which on subsequent dehydration gives rise to p-
cymene as follows:

(b) Reduction: Menthol on reduction with hydroiodic acid yields p-

menthane as under:

Chemical Tests

1. When 10 mg crystals menthol are first dissolved in 4 drops of

concentrated sulphuric acid and then a few drops of vanillin sulphuric acid
reagent are added it shows an orange yellow colouration that ultimately
changes to violet on the addition of a few drops of water.

2. A few crystals of menthol are dissolved in glacial acetic acid and to this
solution a mixture of 3

drops of H2SO4 and 1 drop of HNO3 are added. It fails to produce either
green or bluish green colouration (Thymol gives a green colouration).

3. Menthol provides a plethora of compounds of diagnostic value for

differential identification, for instance: menthoxy acetate; p-
nitrobenzoate; d-camphor sulphonate; acid phthalate; phosphoric
acid-complex; and 3,5-dinitrobenzoate.

Uses

1. It is used profusely in various types of mouth washes, toothpastes and

similar oral formulations.

2. It finds its enormous use as a flavouring agent for chewing gums,

candies, throat lozenges and also certain mentholated cigarettes.

2.1.4 Thymol
Synonyms Thyme camphor; m-Thymol; 3-p-Cymenol; 3-Hydroxy-p-
cymene;

Biological Sources It is obtained from the essential oil of Thymus

vulgaris L., (Thyme oil); Monarda punctata L., (Horsemint
oil), and Monarda didyma L., (Oswego tea oil),belonging to
family Lbiatae. It may also be derived from Carum capticum Bentham er
Hooker, (Ajowan oil), belonging to family Umbelliferae, and several species
of Ocimum,for instance: Ocimum gratissimum L. (Tulsi oil), belonging to
family Labiatae.

Geographical Source T. vulgaris is grown and cultivated abundantly in

many parts of Europe, Australia and North Asia.

Preparation Thymol may be extracted from thyme oil by agitation with

dilute aqueous alkali solution (= 5% w/v in water). The aqueous layer is first
separated and subsequently made acidic with dilute acid, when thymol gets
separated as an oily layer floating on the surface that may be recovered
either by extraction with ether or by steam distillation.
 Another means of obtaining thymol from thyme oil is to subject the
latter to very low temperature (–25oC) when thymol separates as crystals.

Synthetic Thymol The thymol of commerce may be prepared

synthetically by anyone of the following routes, namely:

(a) From Menthone: Menthone is first treated with bromine. and then
quinoline to produce thymol:

(b) From m-Cresol: m-Cresol on being treated with isopropanol in the

presence of a suitable catalyst yields thymol.

(c) From Piperitone: When pipertone, usually obtained from the

Australian Eucalyptus oils, is treated with ferric chloride it gives rise
to thymol.
 Description

Colour : Transparent, colourless

Odour : Aromatic thyme—like odour

Taste : Pungent taste

Solubility : In water (1: 1200); in alcohol (1:1), in glycerol (1: 1000);

Freely soluble in ether, chloroform, carbon disulphide, benzene and glacial
acetic acid; soluble in fixed oil and volatile oil.

Chemical Structure The phenolic OH moiety present in thymol enables

it to form salts of acetate and carbonate easily which are used as antiseptic
and anthelmintic respectively.

Thymol when disolved in NaOH solution and treated with an I2-KI solution
it forms thymol iodide that finds its use as an anti-infective and antifungal
agent.
 Chemical Tests

1. Thymol when fused with phthalic anhydride develops bright violet red
to intense red colouration, and on adding dilute alkali it gives an intense blue
coluration due to the formation of thymolphthalein.

2. Thymol on being dissolved in concentrated sulphuric acid yields the

corresponding thymesulphuric acid [C6H2(SO3H) (CH3). (C3H7).OH], which
produces a distinct violet colour with ferric chloride solution.

3. An alcoholic solution of thymol on being treated with FeCl3 solution

does not produce any colouration.

Note: Carvacrol on identical treatment gives a green colouration.

4. A small crystal of thymol is dissolved in 1 ml of glacial acetic acid and

to this is added one drop of HNO3 and six drops of sulphuric acid, when it
exhibits a deep bluish green colour.

5. Dissolve 0.1 g of thymol in 2 ml of NaOH solution (10% w/v) and heat

in a water bath to produce either a clear colourless solution or a pale red
solution, that ultimately turns darker in shade on keeping without the
separation of oily drops. If the resulting solution is shaken with a few drops
of chloroform it gives a violet colouration.

6. Thymol forms definite derivatives with various reagents e.g.,

napthylurethane derivative (m.p.160oC); phenylurethane derivative (106-
107oC).

Uses

1. It is invariably employed as an antifungal and antibacterial agent.

 2. It is a vital component in several analgesic and topical antiseptic
formulatios in low concentrations ranging between 0.1 to 1% in personal
health care products.

3. It is widely employed in preparation exclusively intended for

mouthwashes, gargles, oral preparations and as a local anaesthetic in
toothache.