Terpenoids

Introduction

Classification and structure

Physical and chemical properties

Extraction and isolation

Identification and sources

Pharmacological activity

Crude drugs

Mention the name, synonym, biological origin, active constituents, uses, precautions, adverse reactions and symptoms of poisoning

Terpenoids containing medicinal plants and their uses

Learning objectives

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8 3

The student should be able to

Describe the definition, chief structural types, classification,

biogenetic origin of diterpenes, triterpenes and steroids

drugs.

Enumerate the applications of diterpenes, triterpenes and

steroids drugs.

Mention the name, synonym, biological origin, active

constituents, uses, precautions, adverse reactions and

symptoms of poisoning Taxus a diterpene containing drug used

therapeutically

Learning outcomes

4

Pharmacognosy by W.C. Evans. Trease and Evan’s, 12th edition.

London. Page Number 23-153; 170-205; 250-289.

Pharmacognosy Phytochemistry by Jean Bruneton, Medicinal Plants

(1999) Page Number 5-73; 91-256; 312-345

Pharmacognosy and Pharmacobiotechnology (1996) by Page

Number 1-40; 59-121.

Phytochemical Methods, J. Harborne PDR for Herbal Medicines

2nd edition 30-75; 77-156.

Organic Chemistry by IL Finar Page Number 368-473; 170-205;

250-289

References

The terpenoids, sometimes called isoprenoids, are a large

and diverse class of naturally occurring organic chemicals

similar to terpenes.

It is also called lipids.

These lipids can be found in all classes of living things, and

are the largest group of natural products.

Derived from five-carbon isoprene units assembled and

modified in thousands of ways.

Most are multicyclic structures that differ from one

another not only in functional groups but also in their basic

carbon skeletons.

Introduction

Plant terpenoids are used extensively for their

aromatic qualities.

They play a role in traditional herbal remedies and

are under investigation for antibacterial,

antineoplastic, and other pharmaceutical functions.

Terpenoids contribute to the scent of eucalyptus,

the flavors of cinnamon, cloves, and ginger, the

yellow color in sunflowers, and the red color in

tomatoes. 6

Introduction

Terpenes contain carbon atoms in multiples of five

They are made by joining together 5-carbon isoprene

units

Oxygen-containing terpenes are sometimes called

terpenoids

When we discuss the terpenes we are most interested in

the carbon skeleton.

Terpenes

Gymnosperm

Angiosperm

Fungi

Marine organisms

Pharmaceuticals, perfumery, soaps, cosmetics, foods and

beverage industries etc.

Antiseptic, stimulant, carminative, diuretic, analgesic etc.

Insecticides, deodorants

Distribution and Sources

Medicinal Uses

Circulation system

Digestive system

Respiration system

Nervous system

Anti-tumour

Insecticide

Therapeutic Uses

Terpenes are hydrocarbons resulting from the combination of

several isoprene units.

Terpenoids can be classified according to the number of

isoprene units used

1. Hemiterpenoids, 1 isoprene unit (5 carbons)

2. Monoterpenoids, 2 isoprene units (10C)

3. Sesquiterpenoids, 3 isoprene units (15C)

4. Diterpenoids, 4 isoprene units (20C)

5. Sesterterpenoids, 5 isoprene units (25C)

6. Triterpenoids, 6 isoprene units (30C)

7. Tetraterpenoids, 8 isoprene units (40C)

8. Polyterpenoid with a larger number of isoprene units

Classification of terpenoids

Isoprene rule

Carbon skeleton of two isoprene units with a bond

between the tail of one the head of another

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Isoprene rule

A sesquiterpenoids found in the waxy coating on the apple skins

Spearmint oil a monoterpenoids

Head

Isoprene

Introduction to Natural Products

Head

Tail

Head

Tail

Isoprene

Introduction to Natural Products

Head

Tail Head

Tail

Isoprene

Introduction to Natural Products

Class Name Carbon Number Isoprene Units

Monoterpene 10 2

Sesquiterpene 15 3

Diterpene 20 4

Triterpene 30 6

Terpene Classifications

Squalene:

Triterpene

It is a precursor of steroid molecules

Lycopene and β-carotene are tetraterpenes

called carotenoids

Monoterpene Examples

CH 2 OH O

O OH

O O

Myrcene Geraniol a -Terpinene Cineole

Menthone Menthol Carvone Thujone

CH2OH OH

O

O O

OH

Farnesol Eudesmol Bulgarene

Atractylone Caryophyllene Aromadendrene

Germacrone Linderene

Sesquiterpene Examples

CH2OH

COOH COOH

O

OHO

O

Phytol

Pimeric acid Kaurene Abietic acid

Marrubin

Diterpene Examples

HO HO HO

CH2OH

Triterpene Exampes

O

OH

Limonene Camphor α-Pinene

β-Selinene Guaiol

Isoprene Units in Terpenes

O

OH

Limonene Camphor α-Pinene

β-Selinene Guaiol

Isoprene Units in Terpenes

O

OH

Limonene Camphor a -Pinene

b -Selinene Guaiol

Isoprene Units in Terpenes

O

OH

Limonene Camphor a -Pinene

b -Selinene Guaiol

Isoprene Units in Terpenes

O

OH

Limonene Camphor a -Pinene

b -Selinene Guaiol

Isoprene Units in Terpenes

O

Valerane

-Vetivone

Eremophilone

Non-Isoprenoid Terpenes

Extraction:

Steam distillation

Extract with solvent

SFE

Isolation:

Separation based on functional groups:

C=C, C=O, COOH, -COO-, -NH-

Crystallization

Separation: Chromatographic methods

Extraction and isolation of terpenoids

Soxhlet method Maceration method

General properties of Terpenoids

Most of the terpenoids are colourless, fragrant liquids which are

lighter than water and volatile with steam.

A few of them are solids e.g. camphor.

All are soluble in organic solvent and usually insoluble in water.

Most of them are optically active.

They are open chain or cyclic unsaturated compounds having one or

more double bonds.

They undergo addition reaction with hydrogen, halogen, acids, etc. A

number of addition products have antiseptic properties.

They undergo polymerization and dehydrogenation

They are easily oxidized nearly by all the oxidizing agents. On thermal

decomposition, most of the terpenoids yields isoprene as one of the

product.

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Reactions:

Troponoides:

1% FeCl3 red colour

CuSO4 green colour

Iridoids:

Trim-Hill reagent, heat: blue red purple

Shear reagent: yellow brown dark green

Azulenoids:

Sabety reagent: blue green purple

Ehrlich reagent: purple or red

Identification of terpenoids

Diterpene, a type of terpene, is an organic compound

composed of four isoprene units.

It is a natural products especially widespread in plants.

They are also present in some insect and in various animal

organisms.

They have 20 carbon atoms and are derived from

geranylgeranyl pyrophosphate

They have the molecular formula C20H32 .

Diterpenes

Almost all diterpenes are biologically important compounds such as

retino, retinal and phytol.

They are known to be antimicrobial and anti-inflammatory compounds.

They are of fungal or plant origin and are found in resins, gummy

exudates, and in the resinous high-boiling fractions remaining after

distillation of essential oils.

The rosin remaining after distilling pine turpentine, for instance, is rich

in diterpenoids.

Properties

Sources

Chemical Structure of Diterpenes

Diterpenes are classified according to their biogenesis

Acyclic compounds

Cyclic compounds

Acyclic compounds They may be linear like capsaicinoids or comprise a lactone or an oxygen containing ring. Capsaicinoids

Classification of Diterpenes

Cyclic compounds result from two modes of cyclization of the

precursor GGPP

Cembrene A, Monocyclic

Labdane, Dicyclic

Abietic acid, Tricyclic

Tetracyclic diterpenes

Cyclic diterpenoids compounds

The five-carbon compound used for biosynthesis of terpenes is isopentyl pyrophosphate

Biosynthesis of terpenes

Formation of geranyl pyrophosphate

Biosynthesis of terpenes

Some diterpenes have pharmacological activities including:

Antihypertensive

Cardiotonic

Abortifacient

Analgesic and anti-inflammatory

Insecticidal

Cytotoxic and antioxidant activities.

Effects:

The taxin mixture (Taxol, Taxine A and Taxine B) leads to improvement

in the cardiac metabolism.

In higher doses, the drug is cardiotoxic and can lead to tachycardiac

arrhythmia leading to diastolic cardiac arrest.

Taxol is a chemical compound used to treat advanced ovarian cancer. It is

also used an antibiotics.

Pharmacological activities

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The drug is considered as abortifacient and should not be

used during pregnancy.

The drug is severely toxic: 50-100 gm are fatal for an

adult.

Contraindications:

Precautions and adverse reactions:

Drug name: Taxus

Plant name: Taxus baccat

Other names: Yew, Chinwood

Family: Taxaceae

Constituents:

Diterpene ester of the taxane type

(mixture is known as taxin)

Taxine A

Taxine B

Taxol

10-deacetylbacchatin III

Bacchatin III

Flavonoids

Diterpene containing drugs

Symptoms of poisoning:

Vomiting, severe abdominal pain and vertigo

Followed by loss of consciousness, redding of the lips.

Tachycardia and superficial breathing.

Death results from asphyxiation and diastolic cardiac arrest.

Management:

1. Gastrointestinal emptying and use of activated charcoal.

2. Treatment of spasms with diazepam or barbital (i.v).

3. In case of shock, plasma volume expanders should be infused.

4. The administration of lodocaine is effective in cardiac rhythm disorders.

5. Monitoring of kidney function, blood coagulation and liver values is

necessary.

6. Intubation and oxygen respiration may also be necessary.

Overdosage:

Triterpene, a type of terpene, is an organic compound composed

of six isoprene units.

It is a natural products especially widespread in plants.

They are also present in some insect and in various animal

organisms.

They have the molecular formula C30H48.

Chemical Structure of Triterpene

Triterpene

STEROIDS

A steroid is a type of organic compound that contains a characteristic

arrangement of four cycloalkane rings that are joined to each other.

Steroids are modified triterpenes which derived also from squalene by

cyclization, unsaturation and substitution.

The nucleus of all steroids is the tetracyclic C17 hydrocarbon 1,2-

cyclopentanoperhydrophenanthrene (gonane or sterane) substituted by

methyl groups at C10 and C13, as well as an alkyl side-chain at C17.

Steroids may possess a nucleus derived from the former one by one or

more C-C bond scissions or ring expansions or contractions.

Steroids

Corticosteroids - these are

creams and ointments, usually for

controlling rashes and itching.

Estrogens and Progestogens-

relates to female sex hormones

(ex. Birth control).

Androgens-anabolic

steroids used for growth

and development of muscle

tissue and mass.

Types of Steroids

All steroids contain a tetracyclic ring system

Most of the hormones are steroids

Hormones are chemical messengers

Steroids

Methyl groups at C-10 and C-13 are called angular methyl groups

The B, C and D rings are trans fused

The A and B rings are also trans fused in most naturally occurring steroids

Substituents on the same side of the steroid ring system as the angular methyl groups are β-substituents

Those on the opposite side of the plane of the ring system are α-substituents

Cholesterol is a Steroid

Examples of Steroids

Molecular formula C21H28O5 Molecular formula C21H26O5

Plant material 100 gm Yam tuber dried

in an oven

Soxhlet extraction with petroleum spirit

of 250 ml

to block all other compounds by ammonia

solution

to Evaporate of solvent by Rotary

evaporator

to crystalize of steroids by suitable

solvent.

10g/100g yam tuber– high yield–

Economical

Extraction of steroids from plants

Soxhlet method

Since the discovery and synthesis of testosterone in the year of

1930s, anabolic steroids have been used by physicians for many

purposes, with varying degrees of success, for the treatment of:

Bone marrow stimulation

Growth stimulation

Stimulation of appetite and preservation

Increase of muscle mass

Hormone replacement for men with low levels of testosterone

Effective in improving libido for elderly males

Gender Identity Disorder.

Medical Application of steroids