INTRODUCTION TO NATURAL PRODUCTS

Prof. Dr. M. Athar Abbasi

RECOMONDED BOOKS
1. Sujata V. Bhat, Bhimson A. Nagasampagi, Meenakshi Sivakumar;
Chemistry of Natural Products, (2005), Narosa Publishing House,
New Delhi.
2. I. L. Finar; Organic Chemistry, Vol. 2: Stereochemistry and the
Chemistry of Natural Products, (2008), Fifth Edition, Dorling
Kindersley, Pvt. Ltd., New Delhi.
3. J. Mann, Secondary Metabolism, (1987), 2nd Edition, Oxford
University Press, New Yark.

4. Andrew Pengelly, The Constituents of Medicinal Plants, An

Introdction to the Chemistry and Therapeutics of Herbal Medicine,
(2004), 2nd Edition, CABI Publishing, USA.

5. James R Hanson, Chemistry and Medicines, An Introductory Text,

(2006), RSC Publishing, UK.
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 PRIMARY AND SECONDARY METABOLISM

* In the living organism (i.e. in vivo) chemical compounds are

synthesized and degraded by means of a series of chemical
reactions each mediated by an enzyme.

* These processes are known collectively as metabolism, comprising

catabolism (degradation), and anabolism (synthesis).

* All organisms posses similar metabolic pathways by which they

synthesize and utilize certain essential chemical species.

* These essential chemical species include sugars, amino acids,

common fatty acids, nucleotides, and the polymers derived from
them (polysaccharides, proteins, lipids, RNA, and DNA, etc.

* This is primary metabolism, and these compounds, which are

essential for the survival and well-being of the organism, are primary
metabolites.

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* Most organisms also utilize other metabolic pathways, producing
compounds which usually have no apparent utility.

* They are secondary metabolites, and their pathways of synthesis

and utilization constitute secondary metabolism.

* These pathways are as much a product of the genetic make-up of

the organism as are the primary pathways.

* These pathways are perhaps only activated during particular stages

of growth and development, or during periods of stress caused by
nutritional limitation or microbial attack.

* The dividing line between primary and secondary metabolism is

rather blurred.

* There are many obscure amino acids that are definitely secondary
metabolites, while many sterols have an essential structural role in
most organisms and must be considered as primary metabolites.
* The two types of metabolism are interconnected, since primary
metabolism provides a number of small molecules which are
employed as starting materials for secondary metabolic pathways. 3
 NATURAL PRODUCTS

* These are the organic compounds occurring in living organisms e.g.

terrestrial and marine plants, animals and microorganisms.
* Natural products are also known secondary metabolites and these
are derived by unique biosynthetic pathways from primary
metabolites.

* Secondary metabolites in most instances are not directly essential

for normal growth, development or reproduction of an organism
producing them. In this sense they are also secondary.

* Following two examples of typical natural products will help to

clarify the definition.

* Morphine only occurs in two species of poppy, Papaver somniferum

& P. setigerum and although widely used and abused by Man, has no
known fuction in these plants.

* Similarly, Penicillins are produced by few species of fungi, have

great value as antibiotics in the service of man but appear to serve
no useful purpose in the microorganisms that produce them.
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 GENERAL CLASSIFICATION

NATURAL PRODUCTS

Alkaloids Steroids Terpenoids Saponins Flavonoids Lignans Coumarins Other Fatty alcohol &
aromatics acid derivatives
and Macrolides

 3 BASIC METABOLIC PATHWAYS

1. ACETATE (POLYKETIDE) PATHWAY

2. MEVALONATE PATHWAY
3. SHIKIMATE PATHWAY

* Some Natural Products are derived from either of the above

mentioned pathway while some are biosynthesized via mixing of
these metabolic pathways.

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 PLANTS: EVER USEFUL

* Plants have provided various materials to human beings for all his
needs in terms of :
Food, Grains, Fruits, Vegetable, Clothing, Cotton, Shelter, Timber,
Flavours, Fragrances, Ornamental Flowers and Medicine.

 HISTORICAL USE AS A MEDICINE

* The use of the medicinal herbs for curing disease has been
documented in the history of all civilizations.
* The classical texts of Ayurveda, Charaka Samhita and Sushruta
Samhita were written around 1000 B.C.

* The Ayurvedic Materia Medica includes 600 medicinal plants along

with therapeutics.

* Herbs like turmeric, fenugreek, ginger, garlic and holy basil were
(and are) an integral part of Ayurvedic formulations.
* These formulations either incorporate a single herb or more than
one herb i.e. polyherbal formulations. 6
* The drugs were used in crude forms like expressed juice, powder,
decoction or infusion.

* Before the availability of synthetic drugs, humans were completely

dependent on medicinal herbs for prevention and treatment of
diseases.

* In the early days, physicians were not aware of the chemical

constituents in the plants.
* However, they did have knowledge of the active principles
responsible for therapeutic activity.

* In Charaka-Samhita, the classical treatise on Ayurvedic medicine,

the word, virya, is similar to word, potency.
* Drugs had been classified according to the pharmacological
activities, but a comprehensive account of the mechanism of action
was missing.

* Despite the non-availability of scientific procedures, the

advancements made by the some of the ancient healers are
astonishing. 7
* The work on Terminalia chebula (myrobalan) mentioned in Charaka
Samhita is quiet authentic and modern studies have revealed that
the purgative activity mentioned in Ayurveda is justified by the
isolation of chebulic acid, the active constituent of myrobalan.
HOOC
H
COOH
OH Chebulic acid (Split acid)
HO COOH • Proc. Chem. Soc., London, 1957, 341
H • Chem. Pharm. Bull., 1982, 30, 2655
O
HO
O

* Sterneur, who first isolated morphine from Papaver somniferum

(opium poppy) showed that certain phytochemicals produced in
plant cells are responsible for pharmacological activity.

* Later on, other alkaloids isolated from opium poppy were

investigated for their pharmacological activities.

* Codeine showed anti-tussive activity and papaverine possessed

anti-spasmodic activity. 8
 HO MeO
Me O

N
O MeO
O
NMe OMe
NMe
H H

HO HO OMe

Morphine (-) form Codeine (Methylmorphine) Papaverine

Abuse Drug Antitussive activity Antispasmodic activity

• Bentley, K.W., Chemistry of the Morphine Alkaloids, Oxford Univ. Press, OH

1954, 57-97 H3C CH 3
OCH 3

• Fennessy, M.R. et al., Eur. J. Pharmacol., 1969, 8, 261 Cl N O

 RECENT USES OF NATURAL PRODUCTS OH

H
N Cl
CH 3
OCH 3 Tubcurarine
chloride
* Many natural products are still used for general purposes.
* Curare, a plant extract (Chondodendron tomentosum), was used as
an arrow poison by South American Indians. Its component,
tubocurarine, is now used as muscle relaxant in surgery.
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* Ephedrine, the basis of an ancient Chinese remedy for respiratory
ailments, is now used in the treatment of asthma and hay fever.

* The psychoactive compounds, morphine and cannabinoids, have

proved irresistible to mankind through many millennia.

* Caffeine was, and still is, the active principle of many native
beverages.
* In many ways our modern coffee, cocoa, tea and cola are but poor
imitations of these native brews.

* Some of the odiferous and spicy compounds that have been used
through ages, are still in use e.g. linalool (oil of lavender), eugenol
(cloves) etc. OH
O
CH HO CH
H CO
3 3
3
H H3C N
N N
CH3
CH2
 CONCLUSION CH3
Ephedrine
O N N
HO

Caffeine Linalool Eugenol

CH3

The natural products have ever been a significant source of herbal

and synthetic medicines and other necessities of life.
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