B.

Pharm PCG 301:

CHEMISTRY OF NATURAL
PRODUCTS
Introduction to Phytochemistry
(2 hours)
Dr. Ibrahim Malami

Department of Pharmacognosy & Ethnopharmacy, Faculty of Pharmaceutical

Sciences, Usmanu Danfodiyo University, Sokoto

Centre For Advanced Medical Research and Training (CAMRET),

Usmanu Danfodiyo University, Sokoto
 Highlight
Chemistry of Natural
Dr. I Malami
Products

Dr. H.E Dr. S.N Mathias Mrs. ZYIY Prof. A. Uba

Mshelia
Introduction to
Phytochemistry Phytochemistry Phytochemistry
of of Lipids
Carbohydrates
Phytochemistry Phytochemistry
Phytochemistry of Volatile oils
of Glycosides of and Resins
Phytochemistry Enzymes
of Alkaloids 15 hrs 8 hrs

Phytochemistry
14 hrs 2 hrs 7 hrs
of Tannins
 Aims and objectives

 To introduce the scope and significance of plant natural

products in clinical applications

 To introduce the different classes of plant natural products

 Objectives

At the end of this set of lectures, you should:

 Be able to understand and identify the different classes of

plant natural products.

 Be able to understand the nature and properties of various

plant constituents
 Introduction

 The use of natural products (especially terrestrial higher

plants) have long been considered as the alternative to
effective anti-infective agents.

 They played a prominent role in ancient traditional medicine

systems, e.g.,

 Traditional Chinese Medicine – Chinese

 Ayurvedic Medicine – Indians

 Egyptian Traditional Medicine – Ancient Egyptian

 WHO – up to 80% of the world population uses traditional
herbal medicine for primary healthcare.
 25% of modern medicines are made from plants – E.g.,

 quinine – Cinchona spp

 atropine – Atropa belladona
 digitoxin – Digitalis lanata

 paclitaxel – Taxus brevifolia

 aspirin – Salix spp
 morphine – Papava somniferum
 artemisinin – Artemisia annua
 vinca alkaloids – Catharanthus roseus
What differentiate
Phytochemistry and
natural products
???
 Phytochemistry – study of natural chemicals derived from
plant.

 Phytochemistry – derived from the Greek word

 “Phyto” – plant

 Natural products – products of natural origin

 an entire plant that has not been gone through any

processing or treatment other than simple process of
preservation, e.g., drying;

 part of an organism, e.g., leaves or flowers of a plant, or an

isolated animal organ or other organisms, e.g., microbes;
  an extract of an organism or part of an organism, and
exudates;

 pure compounds, e.g., quinine, aspirin, artemisinin,

morphine, physostigmine, cocaine, ephedrine, etc. –
isolated from plants.

 “Natural products” refers to secondary metabolites produced

by any living organism.

 to provide defense against predators e.g., toxic material.

 to attract or warn other species e.g., volatile attractants or
coloring agents.
 Provides most of the pharmacologically active natural
products.

 Secondary metabolites – possess a unique complex chemical

structures and due to their remarkable complexity of their
chemical structures, they exert their pharmacological action by
inhibiting a particular metabolic pathway, e.g. interactions with
macromolecules
 Classification of natural products

ALKALOIDS

 Alkaloids – heterocyclic nitrogen compounds derived from

amino acids.
 Currently – >12,000 known structures, alkaloids represent one
of the biggest groups of natural products.
 Alkaloids are basically nitrogen bases – majorities of the
alkaloids contain a pyridine, quinoline, and isoquinoline or
tropane nucleus and are responsible for physiological effects
in man.
 In nature, the alkaloids exist in many plants: in larger
proportion in the barks, seeds and roots often in combination
with vegetable acids.

 The name of alkaloids end in -ine suffix, e.g., codeine,

atropine, morphine, ergotamine, ephedrine etc..

Properties of alkaloids

 They have basic properties and are alkaline in reaction, turning

red litmus paper blue.
 They exist in solid form like atropine and they contain oxygen.
Some alkaloids like lobeline or nicotine occur in liquid form and
contain carbon, hydrogen, and nitrogen.

 They are readily soluble in alcohol and sparingly soluble in

water. The salts of alkaloids are usually soluble in water.

 The solutions of alkaloids are intensely bitter.

 Common examples of alkaloids with pharmacological
properties:

Nicotine

Physostigmine
Camptothecine
Galanthamine Morphine

Tubocurarine

Codeine
Ephedrine

Quinine Cocaine
GLYCOSIDES

 Glycosides are a group of natural products characterized by

the presence of a sugar portion attached by a special bond to
one or more non-sugar portions.

 Chemically, they contain a carbohydrate (glycone) and a non-

carbohydrate part (aglycone).

 Glycosides are broken down upon hydrolysis with enzymes or

acids to:
 a sugar moiety (glycone); and

 a non-sugar moiety (aglycone) – active portion.

 glycone

aglycone

Cyanide glycoside

 Glycosides are distributed widely in the plant kingdom – occur

in the seeds of pulses, in swollen underground roots or shoots
(yams, sweet potatoes), flowers and leaves.

 Some are toxic, especially cyanogenic and cardiac glycosides.

Properties of Glycosides

 They are colorless, crystalline substances containing carbon,

hydrogen and oxygen.

 They are neutral in reaction.

 They are water-soluble constituents.

 They brake down on hydrolysis to give sugar and a non-sugar
moiety.

 Many plants contain cardioactive or cardiac glycosides – most

widely used cardiac glycoside in congestive heart failure

 Others – stomach ulcers, laxative, muscular pain creams and

ointments to treat burns, skin irritation, etc.
 Common examples of glycosides

Digoxin

Digitoxin
PHENOLS

 Phenols – one of the largest groups of secondary plant

constituents.

 They are aromatic alcohols since the hydroxyl group is always

attached to a benzene ring.

 The names of phenols always end in the letters ‘-ol’.

Properties of Phenols

 Antioxidants, anticancer, antiasthmatic, hypotensive.

 Anticlotting effect, antimicrobial, and antiviral.

 Analgesic and anti-inflammatory, and promotes intestinal

motility, etc.
 The most important of these are gallic acid and salicylic acid.

aspirin
salicylic acid
gallic acid

Curcumin

caffeic acid
TANNINS

 Tannins – water-soluble polyphenolic compounds with high

molecular weight that are present in many plant foods.

 The word tannin has been derived from the ability of plant
extracts to tan leather – ‘Tannin’ – derived from the French
word ‘tanin’ (meaning tanning substance).

 Characteristics – degree of astringency in fruits and usually

taste bitter.

 Distribution: roots, back, stems, seeds, skins (outer layers of

plant tissue) and fruits.
 Tannins – broadly divided into two groups:

 the hydrolysable tannins –

 the non-hydrolysable tannins – condensed tannins

OH

HO O
OH

OH
OH

OH O
HO OH

OH
OH

OH O
HO OH

OH

OH
Properties of Tannins

 Tannins are soluble in water and alcohol.

 They form complex with proteins, carbohydrates, gelatin and

alkaloids.

 They are acidic in nature.

 They have a characteristic feature to tan.

 They can readily react with oxygen radicals.

 Tannins – Antibacterial, antiallergenic, hepatoprotective, anti-

inflammatory, diuretics, vasodilating, antiviral, antioxidant,
anticancer, hypolipidaemic, etc.
FLAVONOIDS

 Flavonoids are important group of

polyphenols – widely distributed
in plant flora.

 They are the most common plant pigments next to chlorophyll

and carotenoids.

 They are recognized as the pigments responsible for leaf

colors as well as for the many shades of yellow, orange and
red in flowers.
 Functions – protection of plant tissues from damaging UV
radiation, acting as antioxidants, enzyme inhibitors, pigments
and light screens.

 Flavonoids can be considered as important constituents of the

human diet

 Quercetin, kaempferol and quercitrin are common flavonoids

present in nearly 70 percent of the plants.

 Soya flavones have recently gained importance due to variety

of pharmacological activities.
 Flavonoids –

 Antioxidant and anticancer

 Antidiabetic

 Antimicrobial and antiviral

 Antihepatotoxins (hepatoprotective)

 Anti-inflammatory
 Antihypertensive (cardioprotective)

 Antisickling properties, etc.

 Example:

OH

HO O
OH

OH

OH

Quercetin Epicatechin

Genistein

kaempferol
Alpinetin
TERPENES (TERPENOIDS)

 Terpenoids are the largest class of natural products – over

40,000 known structures.

 All terpenoid structures may be divided into isoprene (five-

carbon) units containing two unsaturated bonds.

 The number of units incorporated into a particular terpene

serves as a basis for the classification of these compounds.
 Monoterpene (C10H16) – Essential oils, e.g. menthol

 Some monoterpenes are insect attractants (to aid

pollination), others have a broad spectrum of antimicrobial
activity (e.g. Thymol).

 In perfume industries (e.g. Jasmine

plant) – rich in monoterpenoids.

Menthol Thymol Lemonene Β-citronellol

(Mentha) (Thymus) (Lemon) (rose oil)
 Sesquiterpene (C15H24) – Bitter principles, especially
sesquiterpene lactones

 They have properties similar to those of the monoterpenes

– constituents of many of the volatile oils

 The most important sesquiterpene from the pharmaceutical

perspective is the antimalarial product artemisinin.

Artemisinin Dihydroartemisinin Artemether

Artesunic acid
(Artemisia annua)
 Diterpene (C20H32) – Bitter principles, resin acids

 Diterpene – are the most bitter tasting of all terpenoid

compounds.
 Paclitaxel – an example of a former best-selling antitumor
agent, is based on this class of natural products.

Paclitaxel (Pacific Yew tree)

 Triterpene (C30H48) – Steroids and saponins

 The triterpenes are terpenoids with an exceptionally wide

distribution, including man, plants, fungi, bacteria, soft
corals and amphibia.

 Steroids (e.g. testosterone) are very important molecules

with many important functions in mammals, notably as sex
hormones.
 Other types include the sterols (e.g. β-sitosterol), which are
commonly found in plants.
 stigmasterol and sitosterol are used as the starting material
in the production of steroidal drugs.
 Example:

Testosterone Oestradiol Progesterone

Ergosterol

β-sitosterol Hydrocortisone
 Tetraterpene (C40H64) – Carotenoids
 Members of this class are sometimes referred to as
carotenes or carotenoids because of their occurrence in the
carrot.

 Highly pigmented natural products and are responsible for

the very bright colors of certain plants – orange of carrots
due to β-carotene.

 The brilliant red colour of tomatoes and peppers – due to

lycopene and capsanthin, respectively
β-Carotene

Capsanthin

Lycopene
SAPONINS

 Saponins are compounds whose active portions form

colloidal solutions in water – produce lather on shaking and
precipitate cholesterol.

 They occur as glycosides whose aglycones are triterpenoid

or steroidal structures.

 They have soap-like

properties and readily
form foams.
Glycyrrhizic acid
POLYSACCHARIDES

 Polysaccharides (glycans) – high-molecular-weight polymers

consisting of chains of sugars (e.g., glucose).
 The simplest polysaccharides are cellulose and starch, which
are polymers of glucose only
 Functions – food storage, protection of membranes, and
maintaining rigidity of plant cell walls.

 Gums and mucilages – products of plant polysaccharides

 Act as Laxative and antidiarrhoeal, ↓cholesterol, ↓blood sugar,
demulcent effects, immunomodulatory effects, antitumour
activity, etc.
 OTHER SOURCES OF NATURAL PRODUCT

ESSENTIAL OILS (VOLATILE OILS)

 Essential oils are odorous principles stored in special plant

cells – glands, glandular hairs, oil ducts or resin ducts.

 These oils are responsible for the distinctive aromas

associated with individual plant species.

 Most essential oils are colorless.

 Used in the form by aromatherapists

 Chemical composition – terpenoids, Phenylpropanoids,

phenols, sulfur compounds, etc.
FIXED OILS

 Fixed oils are composed of fatty acids, hydrocarbon chains

with a methyl (CH3) group at one end, and a carboxyl group
(COOH) at the other end.

linoleic acid

 Apart from their nutritional value – widely used for specific

therapeutic purposes, associated with cardiovascular,
autoimmune, cancer and numerous other chronic diseases.
 Case studies: Lorenzo’s oil
 A combination of oleic acid and erucic acid (4:1) – rapeseed
oil and olive oil.

 Use for the management of adrenoleukodystrophy (ALD).

 To normalize the accumulation of the very long chain fatty

acids in the brain thereby slowing the progression of ALD.

oleic acid

erucic acid
RESINS

 Resins are solid, brittle substances secreted by plants into

special ducts in response to damage to the plant.

 Their main role appears to be protection of the plant from

attack by fungi and insects.

 Resins are difficult to classify because of

their amorphous nature; they are complex
mixtures that include lignans, resin acids,
resin alcohols, resinotannols, esters and
resenes.