this lecture is regarding natural products chemistry

1. Natural Products
Chemistry
(CHEM4119)

3. Natural products
• The compounds which are isolated from natural
sources like plants, animals, fungi, bacteria and lichens
are known as natural products.
• These natural products are the end product of
organism metabolism called metabolites, which
perform different functions in animals and plant.
• Metabolites: the intermediate end products of
metabolism, these are usually small molecules.
• Natural products are often divided into two major
classes: primary and secondary metabolites.

4. • Secondary metabolites : Secondary metabolites in contrast
are organic molecules that typically have an extrinsic function that
mainly affects other organisms outside of the producer. Secondary
metabolites are not essential for organism survival but do increase
the competitiveness of the organism within its environment.
Secondary metabolites have a diversity of structures and include
examples such as alkaloids, phenylpropanoids, polyketides and
terpenoids,
• Primary metabolites: are organic molecules that have an
intrinsic function that is essential to the survival of the organism
that produces them (i.e. the organism would die without these
metabolites). Examples of primary metabolites include the core
building block molecules (nucleic acids, amino acids, sugars, and
fatty acids) required to make the major macromolecules (DNA,
RNA, proteins, carbohydrates, and lipids) responsible for
sustaining life.

5. • Natural products are often classified based on major structural
features. Four of the major classes of natural products are the
alkaloids, which are organic molecules that contain nitogen,
the phenylpropanoids which are derived from the amino
acids phenylalanine or tyrosine, the polyketides derived from
acetate and malonate, and the terpenoids, derived from the
five-carbon building block, isoprene.
• The process of searching for and finding new natural products
throughout the world is called bioprospecting and the
discipline that elucidates the structure of natural products and
studies their biological activity is called pharmacognosy.

6. Different sources of Natural
products
• Plants
Plant is one the major source of natural products. the natural
products isolated from the plants depends on Plant specie: different
species produce different metabolites.
• Variability in growing conditions:
Different growing condition also result different metabolites in the same
species. Different part of the plants mostly contained different
metabolites.
• Microbes
Bacteria and microbes are the important source of natural products.
The fermentation, followed by purification results some useful
natural products. These natural products are very useful as antibiotic.

7. • Marine organisms
• Marine organism are also important source of natural products. However
their collection is more challenging than plants.
• The chemistry of marine natural products will be influenced by different
variables, for example, currents and sediments, pH levels,
atmospheric
constituents, metamorphic activity, and ecology .
• Curacin A is obtained from a marine cyanobacterium and shows potent
antitumor activity.
• Animals
• Animals also yield natural chemicals which are important.
• Potent analgesic compound called epibatidine has obtained from the
poisonous
skin extracts of the Ecuadorian frog.
• The snake venom and toxin also contained some useful peptides based
natural products. These peptides based natural products have
specific interaction with macromolecules and cells. Like bungarotoxin from

8. Major classes of organic natural
products
• Peptides and proteins (basically consist of
amino
acids)
• Fats and oils
• Nucleotides (purines)
• Vitamins
• Steroids
• Terpenes (terpenoids)
• Carteins (Carotenoids)
• Anthocyanines
• Alkaloids

9. Alkaloids
• Alkaloids are physiologically active nitrogenous compounds
which nitrogen is usually present in ring system.
• Originally the name alkaloids ( alkali like) was given to all
organic bases isolated from plants.
Historical development of definition of alkaloids
• Konigs (1880) that alkaloids should be defined as naturally
organic bases which contain a pyridine ring. This definition,
however covered a small number of alkaloids.
• Ladenburg defined alkaloids as natural plant compounds
having a basic character and containing at least one nitrogen
atom in heterocyclic ring. This definition covered both synthetic
and naturally occurring compounds.

10. Alkaloids
Limitation of this definition:
• Some alkaloids are not basic in nature like Colchicine, Piperine,
Quaternary alkaloids.
• In all alkaloids the nitrogen atom is not part of a ring e.g. Ephedrine,
Colchicine, Mescaline.

11. Alkaloids
Definition of alkaloids
• Alkaloids can be define as any nitrogenous organic
compounds of plant origin, which have pronounce
physiological action on human and other animals.
History of alkaloids
• The history of alkaloids is old as the human civilization.
• Most of the alkaloidshave been used in potions, medicines,teas, poultices
and
poisons.
• Opium was isolated from Papaver sominferum which exhibit analgesic and
narcotic
properties.
• In 1805 serturner led to the isolation of morphine from opium and it was
serturner who first discovered the basic character

12. • From 1817-1820, in the laboratory of
Pelletier and Caventou at the faculty of
pharmacy in Paris, isolated many alkaloids brief period.
• These alkaloids were strychnine, emetine, brucine,
piperine, caffine, quinine, cinchonine and colchicine.
• In 1826, Pelletier and Caventous also obtained coniine, an
alkaloid of considerable historical importance which caused
death of Socrates.
• It was the first alkaloid to be characterized
structurally (1870) and synthesized for the first time in
1886.
coniin Coniine’s Plant

13. • The molecular complexity of the majority of these alkaloids
precluded their structure elucidation during the 19th
Century or even in the early 20th century.
• The case of strychnine is good example. First obtained by
Pelleti er and Caventou in 1819, it took nearly 140 years of
extremely hard work and very frustrating chemical
investigations before the structure was finally determined in
1946 by Robinson and co-worker.
• 1939- nearly 30 alkaloids had been isolated. 200 of these
and fairly elucidated structures.
• 1950- Mankse’s alkaloid series reported more than 1000
alkaloids.
• 1993- A review counted 4959 alkaloids of which 3293 had
known structure.
• 1978- the number of structurally defined alkaloids stood 4000.

14. Classification of alkaloids
True alkaloids
• They are invariably basic, show wide range of physiological
activity, highly toxic normally contained nitrogen in
heterocyclic ring, are derived from amino acids, have limited
taxonomic distribution, and occur in plants as salt of organic
acids.

15. Proto alkaloids
• The proto alkaloids are relatively simple amines in which
nitrogen is not in the ring.
• They are bio-synthesized from amino acids and are basic in
nature.
• The term ‘biological amines’ is often used for the
group of compounds. Example are Mescaline,
Ephedrine, N,N-dimethyl- trypatamine.

16. Pseudo alkaloids
• Theyare not derived from amino acid precursors. They
are usually basic.
• There are two important types of pseudo alkaloids
• Steroidal alkaloids e.g.. Conessine
• Purines, e.g., Caffeine

17. Isolation and purification of alkaloids
The Procedure and Methods
1 Selection of Green and Fertile land
Natural habitat of plant is selected for plant collection.
2 Identification and collection of plant
Help can be taken from botanist or expert local people.
Plant must be free from wild plants, otherwise will effect quality or
might be toxic.
3 Separation Drying of plants parts
Different part of plant (root, stem leaves and flower) are
separate
d. Plant parts are dried under shade.

18. Isolation and purification of alkaloids
Extraction procedure:
- The dried plant is crushed and grind into powder.
Defatting:
- Crushed and powder plant materials is soaked in petroleum
ether and n-hexane to remove unuseful constituents like oil,
terpenes and fats.
Extraction:
- The plant material are soaked in different organic solvent (
methanol, ethanol)to extract different compounds from plant
materials for a couple of week or may be for months.

19. Isolation and purification of alkaloids
• Liquid-liquid extraction:
- In liquid-liquid extraction also known as solvent extraction,
different compounds are separated based on their solubility in
different solvents.
- These two solvents are immiscible, usually water (polar)
and non- polar (organic solvents).
- The separation is driven by relative solubility in different
solvents.
• Rotary evaporation:
- The extracted compounds are filtered to separate from
plant materials.
- The extract is concentrated with help of rotary by evaporating

20. Isolation and purification of alkaloids

21. Purification
• The initial extraction give a crude mixture of alkaloids, which is
further subjected to purification to semi-pure or completely pure alkaloids.
• The purification efficiency depends on the number of components
present in the mixture, the extract contain one or two alkaloids is
easy, but if the components are more then effective separation is
difficult.
• Methods used for purification
• Different methods like steam distillation, fractional distillation,
fractional cr ystallization, and fractional precipitation were in common in
practice. But these
methods are not so advantageous. The most effective method
is
chromatography.
• The chromatography methods included thin layer chromatography, gas
liquid chromatography, column chromatography. These chromatographic
methods are used alone or in combination with thin layer and gas liquid
chromatography.
• Column chromatography is most commonly used method.

22. Purification
• Column Chromatography
Column chromatography is one of the most efficient and useful methods for
separation of solids and liquids.
Stationary Phase- Solid stationary phase packed in
column. Mobile Phase- Liquid mobile phase passing
through the column. Principal of Separation:
The separation take place based on partition of different fraction between
mobile phase and stationary phase.

24. Analyzing the component
• Colored Fraction- observed visually
• Non- colored Fraction- is analyzed with by developing TLC
and TLC is observed under UV lamp
• Number of spot appear on TLC plate under UV lamp show the
nature of fraction---pure/impure
• Locating reagent are used to locate UV inactive compound