Alkaloids

-Organic nitrogenous compounds with a limited distribution in nature.

-Most possess basic properties and mark physiological activity.

-The nitrogen may exist as a primary amine (RNH2), as a secondary

amine (R2NH), as a tertiary amine (R3N), or as a quaternary amine

(R4N+X-).

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1. From the generic name of the plant

yielding them (hydrstine, atropine).

2. From the specific name of the plant

yielding them (cocaine, belladonine).

The names of the alkaloids are obtained in various ways:

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3. From the common name of the plant yielding them (ergotamine).

Ergotamine

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4. From their physiological activity (emetine, morphine).

emetine morphine

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5. From the discoverer (pelletierine).

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Function of alkaloids

• Protection

• End products of detoxification

• Regulatory growth factors

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Pharmacological action of alkaloid

• Analgesics and narcotics (morphine)

• Central stimulants (nicotine)

• Mydriatics (atropine)

• Miotics (physostigmine, pilocarpine)

• Hypertension (ephedrine)

• Hypotension (reserpine)

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Some Examples of Alkaloids

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10Antihypertensive

Classes of Alkaloids:

Tropane Alkaliods

N

Tropane

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Occurrence

Belladonna leaf (Deadly nightshade leaf)

-Consists of the dried and flowering top of Atropa belladonna

(Solanaceae) Atropa: Greek Fate who cuts the thread of life.

-Belladonna: from Italian bella, meaning beautiful, and donna,

meaning lady. (The juice of the berry, when placed on eyes, causes

dilation of the pupil thus giving a striking appearance.)

-3/4 of the alkaloid mixture is (-)-hyoscyamine; 1/4 is atropine,

which is formed by racemization during extraction. 12

-

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Hyoscyamine

Uses: parasympathetic depressant (spasmolytic agent);

used as adjunctive therapy in the treatment of peptic ulcer;

functional digestive disorders, including spastic mucous and

ulcerative colitis;

diarrhea;

pancreatitis;

control excess motor activity of urinary tract.

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Hyoscyamus leaf

-dried leaf and flowering and fruiting top of Hyoscyamus niger

(Solanaceae).

-contains 3/4 of hyoscyamine and 1/4 of scopolamine.

Uses: parasympathetic.

Stramonium leaf

-dried leaf and flowering and fruiting top of Datura strmonium

(Solanaceae). -contains principally hyoscyamine with small portion

of scopolamine and trace of atropine.

-Uses: anticholinergic. 15

Hyoscyamine

-usually obtained from species of Hyoscyamus or other genera of

Solanaceae.

-readily hydrolyzed by boiling in dilute acids or alkalies to form

tropine and tropic acid

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Scopolamine

Anticholinergic;

• central nervous system depressant used for preanesthetic sedation

and

• for obstetric amnesia in conjunction with analgesics;

prevention of nausea and vomiting associated with motion sickness.

NO

H O O

O

S c o p o la m in e

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-obtained from the leaves of Erytroxylum coca and its variety or

prepared by semisynthesis from plant-derived ecgonine.

Erytroxylum: from Greek, meaning red wood

coca: Spanish name for tree.

-cultivated in Bolivia, Colombia, and Peru; each produces about

50,000 metric tons of leaves a year.

Cocaine

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Uses: local anesthetic.

Other physiological effect:

• powerful central nervous system stimulant with a strong abuse potential;

• euphoric excitement is rapidly produced when cocaine is sniffed.

-acute toxicity from excess dose:

• extreme agitation, restless, confusion, blurred version, and tremors;

• induces paranoid thinking, hallucinations, cardiac arrhythmia, acute

myocardial infartion.

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Quinoline alkaloids

N

quinoline

Cinchona bark (Peruvian bark)

-dried bark of the stem and the root of Cinchona succirubra or its hybrids, or

other species of Cinchona and their hybrids.

Cinchona: named in honor of the countess of Chinchon.

succirubra: means juice.

-indigenous to the Andes of Ecuador and Peru. 20

• grow at an elevation of 1000 to 3000 meters, cultivated in

Indonesia and India.

• trees that are 6-9 years old possess the maximum amount of

alkaloids.

• contained some 25 closely related alkaloids, the most

important of which are quinine, quinidine, cinchinine, and

cinchonidine.

• uses: treatment of malaria fever.

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Quinine

• obtained from bark of Cinchona species.

• use: antimalarial

• mechanism: intercalation of the quinoline moiety into the DNA

of the plasmodium parasite.

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• obtained from bark of Cinchona species.

• a stereoisomer of quinine.

• use: treatment of cardiac arrhythmias.

Quinidine

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Isoquinoline alkaloids

Emetine

• uses: antiamebic by inhibiting polypeptide chain elongation;

possesses expectorant and emetic properties. 24

Opium Alkaloids

• air-dried milky exudates obtained by incising the unripe capsules of Papaver

somniferum (Papaveraceae).

• opium: Greek, meaning poppy juice.

• Papaver: Latin, means poppy.

• somniferum: Latin, means to produced sleep.

• an annual herb with large, showy, solitary flowers that vary in color from white

to pink or purple. 25

• first cultivated in Mediterranean region, then introduced into

India by Alexander the Great.

• cutivation is controlled internationally by the International

Narcotics Control Board of the United Nations.

• contain morphine, codeine, noscapine, papaverine, and thebaine.

• uses: analgesic hypnotic, narcotic,

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• the most important opium alkaloid.

• contains a phenolic and an alcoholic hydroxyl group.

• used as narcotic analgesics; strongly hypnotic and narcotic; induced nausea,

vomiting, constipation, and habit formation.

Morphine

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Heroine (Diacetylmorphine)

• formed by acetylation of

morphine.

• More potent than morphine.

Hydromorphone

6-OH replaced by a ketone.

• more potent than morphine.

• less nausea and constipation. 28

• obtained from opium or prepared by

morphine methylation.

• anticough

Codeine

NH

OMe

OMe

MeO

MeO

Papaverine

• occurs in opium

• smooth muscle relaxant.

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H

N

O O

CH3

MeO

6

Hydrocodone

• anticough

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The biosynthesis of alkaloids has been extensively studied, although

it was previously thought that alkaloids arose primarily from amino

acid precursors,

strong evidence is now available that ethanoate also is involved.

The mode of alkaloid biosynthesis is not yet as well understood as

that of the terpenes and steroids.

Biosynthesis of alkaloids

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Anabasine, C10H14N2 is an alkaloid which is isomeric with nicotine and

also found in tobacco. Like nicotine it is used as an insecticide.

The biosynthesis of (-) anabasin is as follows:

• Amino acid, lysine is enzymatically converted to cadaverine and 5-

aminopentanal

• It cyclises to 3,4,5,6-tetrahydropyridine.

• It then reacts with partially hydrogenated nicotinic acid (I), which is

formed by the action of NADH, giving an addition product (II).

• Under the influence of ADP+ it is dehydrogenated and decarboxylated to

give (-) anabasin.32

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