Alkaloids

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Mohammed N. Sabir

Reference books 1-James E. Robbers, Marilyn K. Speedie, Varro E. Tyler:

Pharmacognosy and Pharmacobiotechnology 1996.

2-Trease and Evans W.C.: Pharmacognosy. 15th ed. 2002.

3-Medicinal Natural Products a Biosynthetic approach. 1998

4-Bhat S.V., Nagasampagi B.A., Sivakumar M.: Chemistry of

natural products 2007.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Definition and Introduction…

Pharmacognosy II – Third Year Lecture 2 Alkaloids

History of alkaloids…

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Occurrence in nature…

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Specific alkaloids are confined to specific

plant families:-

1-Hyoscyamine in Solanaceae.

2-Colchicine in Liliaceae.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

3-Nicotine, which is found in a number of

widely scattered plant families, is an exception

to this rule.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

4-Ergot alkaloids occur in the fungus (Claviceps

purpurea and certain Ipomoea species),

(Convolvulaceae) is also an exception.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

-Alkaloids may occur in various parts of the

plant; in seeds (physostigmine, areca),

underground parts (sanguinarine), rhizomes and

roots (ipecac, hydrastis), barks (cinchona).

They are also found in fungi (ergot).

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Physicochemical properties…

Pharmacognosy II – Third Year Lecture 2 Alkaloids

- The basicity of the alkaloids varies according to the

location of the amine.

- The quaternary amines varies from other alkaloids in

their physicochemical properties.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Extraction of alkaloids…

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Identification of alkaloids… Precipitation tests

1-Mayer’s reagent.

2-Wagner’s reagent.

3-Tannic acid solution.

4-Hager’s reagent.

5-Dragendorff’s reagents.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Nomenclature of alkaloids…

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Classification of alkaloids… Alkaloids are usually classified by their common

molecular precursors (basic chemical structures from

which they are derived), based on the metabolic

pathway used to construct the molecule.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Ex:- Opium alkaloids are sometimes called

"phenanthrenes", or by the plants or animals

they were isolated from.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Pyridine Piperidine pyrrolidine

Tropane

Quinoline

Isoquinoline Indole Imidazole Purine

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Functions of alkaloids in plants…

1- Poisonous agents for protection.

2- End products of detoxification reactions.

3- Regulatory growth factors.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Functions of alkaloids in plants…

4- Reserve substances.

5- Byproducts of metabolism.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Pharmacologic activities of alkaloids…

• Morphine and Codeine are narcotics and analgesics.

• Strychnine and Brucine are CNS stimulants.

• Atropine is anticholinergic agent.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Pharmacologic activities of alkaloids…

• Physostigmine and Pilocarpine are muscarinic

blockers and mitotic.

• Ephedrine is adrenergic agonist.

• Reserpine causes rapid drop in blood pressure (used

in essential hypertension) and antipsychotic.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Pharmacologic activities of alkaloids…

• Vincristine and Vinblastine are anticancers.

• Ergot alkaloids are vasoconstrictors (used in

migraine), and uterine muscle convulsant (used in

uterine bleeding).

• Colchicine is used in gout.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Biosynthesis of alkaloids…

All alkaloids are derived from amino acids, mainly

(phenyl alanine, tyrosine, tryptophan, histidine,

anthranilic acid, lysine, and ornithine)

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Biosynthesis of alkaloids…

The general reaction include (decarboxylation

and transamination) to yield the corresponding

amine or aldehyde.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

-These can react to form a Schiff base which, in

turn, reacts with a carbanion in a Mannich-type

condensation.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

- CO2 COOH R CH2NH2 R CHNH2

α-amino acid R' + -H2O RN H C 3

Schiff base COOH transamination R' CHO R' CHNH2

H - CO2 α-amino acid

R' CH RNH

+

H C H

R'' Carbanion

R' CH

R'' RNH

Alkaloid

General reactions in alkaloid biosynthesis

Pharmacognosy II – Third Year Lecture 2 Alkaloids

1 Alkaloid derived from Ornithine

L-Ornithine is none-protein amino acid forming part of

the urea cycle in animals.

Plants

Pharmacognosy II – Third Year Lecture 2 Alkaloids

-Ornithine contains both δ- and α-amino groups,

and it is from the former group which is

incorporated into alkaloid structures along with

the carbon chain, except for the carbonyl group.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

-Thus ornithine supplies a C4N building block to

the alkaloid principally as a pyrrolidine ring

system, but also as part of the tropane alkaloids.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

1.1 Pyridine-Piperidine alkaloids

Divided into 3 subgroups:

•Piperidine including (Lobeline from Lobelia).

•Derivatives of nicotinic acid, including Arecoline from

Areca.

•Derivatives of both pyridine and pyrrolidine, including

Nicotine from Tobacco.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Biosynthesis of Pyridine-

Piperidine alkaloids

H2N H NH2

COOH

L-Ornithine

Ornithine

decarboxylase H2N NH2

Putrescine

S-Adenosylmethionine

Putrescine

N-methyltransferase

H2N NHCH3

N-methylputrescine

HCNHCH3O

N-Methylaminobutanal

N

CH3N-Methylpyrrolinium Ion

NH

HH

C

OHO

N

CH3N

N

CH3

C

OOH

H

H

H

- CO2

- 2 HN

NH

CH3

(-) Nicotine

N

COOH

Nicotinic acid

N

COOH

COOH

Quinolinic acid

N

COOH

COOH

HOCOOHH2C

CHCOOHH2N

+CH2OH

HOHC

CH2OP

Glyceraldehyde-3-phosphate

Aspartic Acid Biosynthesis of Nicotine

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Areca

Areca nut, or betel nut is the dried ripe

seed of Areca catechu Linne’ (Fam.

Arecaceae).

The fruit is a nut that contains a single

seed with a thin seed coat are removed

from the fruits, boiled in water with

lime, and dried.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

India is a major producer of areca, but its production is

mostly consumed domestically.

Areca is mixed with lime and chewed as a stimulant.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

In pharmaceuticals the dried betel nut is used as

anthelminitc in veterinary practice and is employed as a

vermicide and taeniafuge.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

The stimulant action of arecoline is attributed to its

agonistic actions on M1, M2, M3 parasympathetic

receptors in brain.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

-Areca contains arecoline (arecaidine methyl ester).

-The total alkaloid content can reach 0.45%.

-Arecoline, the most abundant and psychologically

most active alkaloid.

-It is a liquid occurring to the extent of about 0.2%.

-Areca extract also contains tannins (about 15%), lipids,

volatile oils, and gum.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Nicotine

Is a pyridine-pyrrolidine alkaloid obtained from the

dried leaves of the tobacco plant Nicotiana tabacum

Linne’, N. rustica (Fam. Solanaceae).

The leaves contain from 0.6-0.9% nicotine and less

amount of nornicotine.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Major alkaloids found in tobacco

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Nicotine is colorless to pale yellow,

very hygroscopic, oily, volatile liquid

with an unpleasant, pungent odor

and a sharp, burning, persistent

taste.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Nicotine is a ganglionic (nicotinic) cholinergic-receptor

agonist.

Chronic use of nicotine may result in psychologic and

physical dependence.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Nicotine stimulates the reward center and drug-

reinforcement behavior in the brain.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Actions…

- Brain

- CVS

- Kidneys

- Liver

- Metabolism

- Cancer

- Pregnancy

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Nitrosamine and cancer…

As a temporary aid for the cessation of cigarette

smoking, the drug is available in transdermal systems,

and it is also available bound to an ion exchange resin

in a chewing gum base.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Cytochrome- P450

Nicotinamide (niacinamide) or vitamin B3…

Used for deficiency of niacin and pellagra.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Nicotinamide is also used for hyperlipidemia and

topically for treatment of acne.

Pharmacognosy II – Third Year Lecture 2 Alkaloids

Thanks for listening… Any questions?

Pharmacognosy II – Third Year Lecture 2 Alkaloids