PHG 322PHARMACOGONSY IILECTURE 1PRESENTED BYASSISTANT PROF. DR. EBTESAM ALSHEDDI

الرحيم الرحمن الله بسم

Office: second flour # 84

Email: ebtesam.saad@yahoo.com

Site: faculty.ksu.edu.sa/10252

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Topics to be covered: (cont.)

1) Plants containing Alkaloids (botanical and chemical

characters):

Introduction

Phenylalkylamine, Tropolone and Imidazole alkaloids

Pyridine and piperidine alkaloids

Tropane alkaloids

Quinoline and isoquinoline alkaloids

Opium alkaloids

Indole alkaloids

Carboline, purine, steroidal and terpenoidal alkaloids

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Topics to be covered:

2) Marine derived drugs:

Biomedical potential of marine natural products

Microalgae as a drug source

Biologically active substances from marine sponges

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Topics to be covered:

3) Plants containing Glycosides (botanical and chemical

characters):

Introduction

Phenolic, cyanogenic and thioglycosides

Coumarins, flavonoidal glycosides and related

compounds

Anthracene derivatives

Cardiac glycosides

Saponins

4) Toxicological Pharmacognosy:

Poisonous plants

Plants as drugs of abuse

Hepatotoxic plants

Toxic mushrooms

3) Herb-drug interactions

Topics to be covered:

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Important Book/Thesis:

No. Book/Thesis Editor or Author

Date of pub.

Name of Publisher

1Pharmacognosy

16th edition

Trease

and Evans2009

Saunders

London, New York, …

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السامة النباتات

المملكة في

السعودية العربية

بن الله عبد

أحمد

األمير

2000

سعود الملك جامعة

العلوم كلية

واألحياء النبات قسم

الدقيقة

3Bioactive Marine

Natural Products

Bhakuni

and Rawat2005

Anamaya Publishers,

New Delhi, India

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Marks Assessment task

Dr. Rababb Dr. Ebtesam

- 18First ½ of semester

(Exam + Activity/Quiz)

18 - Second ½ of semester

24 Practical

20 20 Final Exam

100 Total

The assessment tasks during the semester:

AlkaloidsDefinition

Alkaloids, which mean alkali-like substances, are basic

nitrogenous compounds of plant or animal origin and generally

possessing a marked physiological action on man or animals.

• The nitrogen is usually contained in a heterocyclic ring system.

Deviation from Definition

1) Some alkaloids are not basic e.g. Colchicine, Piperine,

2) Few alkaloids contain nitrogen in a non-ring system

e.g. Ephedrine, Colchicine. Mescaline

3) Plant origin:

Some alkaloids are derived from bacteria, fungi, insects, frogs, animals.

1) Protective function against insects or herbivores

2) They are end products (detoxification)

3) Source for energy and reserve of nitrogen

Function of alkaloids in plants

DISTRIBUTION IN PLANT:

All Parts e.g. Datura.

Barks e.g. Cinchona

Seeds e.g. Nux vomica

Roots e.g. Aconite

Fruits e.g. Black pepper

Leaves e.g. Tobacco

Latex e.g. Opium

Genus name e.g. Atropine from Atropa

Species name e.g. Cocaine from Coca

Common name e.g. Ergotamine from

Ergot

Physiological activity e.g. Emetine

(emetic)

Discoverer e.g. Pelletierine from Pelletier

Nomenclature

Alkaloids terminate with the suffix: (ine)

Their names may be derived from:

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Prefixes and suffixes

These are, usually, added to the name of the parent

alkaloid and are used to designate related alkaloids,

generally present in the same plant.

I. Prefixes

Examples are:

1) Nor-: designates N-demethylation or N-

demethoxylation e.g. Nornicotine

2) Apo-: designates dehydration e.g. Apomorphine

3) Iso-, Pseudo-, Neo- and Epi- indicate different types of isomers

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II. Suffixes

1) –dine: designates isomerism as in case of the Cinchona alkaloids

quinine (l) & quinidine (d)

cinchonidine (l) & cinchonine (d)

2) –ine: indicates, in case of ergot alkaloids, a lower pharmacological

activity e.g. ergotaminine is less potent than ergotamine

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volatile

e.g. pilocarpine and hyoscine

Some are liquids

Physical properties:

1) Condition:

Most alkaloids are crystalline solids

e.g. nicotine and coniine

non-volatile

Some are coloured:

2) Colour:

- colchicine & berberine yellow

Most alkaloids colourless

- canadine orange 15

3) Solubility:

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Solubility of alkaloids & their salts is important because:

a) They are often administered in solution

b) Differences in solubility between alkaloids & their

salts is used for:

- isolation of

alkaloids

- purification from non-alkaloidal substances

Solvent Alkaloidal bases Alkaloidal salts

Alcohol

Organic solvents

H2O

Soluble Soluble

Soluble

Soluble

Insoluble

Insoluble

- theobromine & theophylline → benzene (insol.)

except:

- morphine & psychotrine → insol. in ether

except:

- caffeine

- ephedrine

- codeine

- colchicine

- pilocarpine

- quat. ammonium bases

quinine sulphate→ insoluble in H2O

except:

except:

- lobeline hydrochloride → CHCl3 (soluble)

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• Optically active isomers may show different physiological activities.

• l-ephedrine is 3.5 times more active than d-ephedrine.• l-ergotamine is 3-4 times more active than d-

ergotamine.• d- Tubocurarine is more active than the corresponding l- form.

• Quinine (l-form) is antimalarial and its d- isomer quinidine is antiarrythmic.

• The racemic (optically inactive) dl-atropine is physiologically active.

4) Optical activity:

Many alkaloids are optically active due to ?

→ presence of one or more asymmetric carbon atom(s)

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coniine

Chemical properties:

Alkaloids contain: C, H, N

Most of them contain oxygen

Few alkaloids are oxygen free

nicotine

CHEMICAL PROPERTIES:I- Nitrogen:

Primary amines R-NH2 e.g. Norephedrine

Secondary amines R2-NH e.g. Ephedrine

Tertiary amines R3-N e.g. Atropine

Quaternary ammonium salts R4-N e.g d-Tubocurarine

II- Basicity:

R2-NH > R-NH2 > R3-N

Saturated hexacyclic amines is more basic than aromatic amines.

1) Nitrogen in alkaloids

Number of

nitrogen atoms

Type of amino

groupBasicity

1) Number of nitrogen atoms:

• Usually one N atom

• Some contain more than one → up to 5 N atoms

e.g. nicotine → two ergotamine → five

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2) Type of amino group:

• N in alkaloids → in form of amine

Primary amino group

Secondary amino group

Tertiary amino group

Quaternary ammonium ion

N

R

HH ..

Norpseudo-ephedrine

e.g.

Ephedrine

NH..R2

R1

N..R2

R1

R3

Nicotine

NR2

R1

R3

R4

+

Tubocurarine

→ form salts with acids without liberation of H2O

3) Basicity:

A lone pair of electrons on N atom → basic character

→ alkaloids resemble NH3 in chemical characters

Alkaloid

N: + H+Cl-

Alkaloid hydrochloride

][ N H Cl -+

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Factors influencing the degree of basicity:

Structure of the molecule

e.g. degree of unsaturation of heterocyclic ring

N. .

Pyridine Piperidine

N. .

Piperidine alkaloids →

more basic than pyridine alkaloids

unsaturation decreases basicity

Presence & position of other substituents &

fuctional groups

Electronreleasing groups

Electronwithdrawing gps

increase basicitydecrease

basicity

e.g. alkyl group

e.g. carbonyl

group

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Morphine

→ Alkaloids may be:

→ electron availability on

nitrogen atom decreases

e.g. phenolic alkaloids

e.g. alkaloids containing carboxylic group

Neutral (not basic)

Amphoteric → due to the presence of acidic group(s)

Narceine 25

Ricinine