PHG 322PHARMACOGONSY IILECTURE 2PRESENTED BYASSISTANT PROF. DR. EBTESAM ALSHEDDI

الرحيم الرحمن الله بسم

Stability: Generally alkaloids are decomposed by heat

except: caffeine sublimes without decomposition

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Effect of Acids:

hot dil. acids or conc. mineral acids may cause:

Dehydration

apoalkaloids

morphinee.g.

apomorphine

O-demethylation

codeine

morphine

e.g.

conc HCl or HI

+ CH3Cl or CH3I

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Hydrolysis of

- ester alkaloids:

e.g. atropine

- glucoalkaloids:

e.g. solanine

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Stability: (cont.) Effect of Acids: (cont.)

hot dil. acids or conc. mineral acids may cause:

Effect of Alkalies:

Effect of weak alkalies

Effect of hot dil. alkalies

Effect of strong alkalies

Stability: (cont.)

liberate most alkaloids from their salts

form salts with alkaloids containing carboxylic groupe.g Narceine + NaHCO3

Na salt

b) Effect of strong alkalies:

salt )phenates(

phenolic alkaloid +aq. NaOH or KOH

cleavage of lactone ring

c) Effect of hot dilute alkalies:

e.g. pilocarpine

hydrolysis of ester alkaloids

e.g. atropine corresponding acid

Pilocarpic acid

Tests for identification:

Precipitation reactions Colour reactions

include two types of reactions:

1 (Precipitation reactions:

precipitating reagent

Coloured ppts )amorphous or crystalline(

aqueous soln. of

alkaloidal salts + )contains heavy metals e.g. Hg, Cd, Bi(… ,

N.B. certain alkaloids do not react e.g. caffeine

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most reagents precipitate: proteins, tannins, …

• false positive results are possible

Classification of Alkaloidal precipitating agents:

1- Reagents that form double salts:

a- Mayer’s Reagent: Potassium Mercuric Iodide.

b- Dragendorff’s Reagents: Potassium Iodobismethate.

c- Gold Chloride.

2- Reagents Containing Halogens:

a- Wagner’s Reagent: Iodine/ Potassium Iodide.

3-Organic Acids:

a- Hager’s Reagent: Picric Acid

b- Tannic Acid.

4- Oxygenated High Molecular Weight Acids:

a- Phosphomolybdic acid

b- Phosphotungestic acid

c- Silicotungestic Acid

Colour Reagents:

1- Froehd’s Reagent: Phosphomolybdic acid

2- Marqui’s Reagent: Formaldehyde/ Conc. H2SO4

3- Mandalin’s Reagent: Sulphovanidic acid

4- Erdmann’s Reagent: Conc. HNO3/Conc. H2SO4

5- Mecke's Reagent: Selenious acid / conc. H2SO4

6- Shaer's Reagent: Hydrogen peroxide / conc. H2SO4

7- Rosenthaler's Reagent: Potassium arsenate / conc. H2SO4

8- Conc. HNO3These tests are sensitive to micro amounts used for colourimetric determination (quantitative)

solid )free base(

colour reagent +)contain conc H2SO4

+ an oxidizing agent(

characteristic colour

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1( Vitalis test for solanaceous alkaloids:

+ conc HNO3 & alc. KOH violet colour

2 (Van-Urks test for ergot alkaloids:

+ PDAB in conc H2SO4 blue colour

-specific for one alkaloid or a group of related alkaloid:

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Pharmacological activity:

wide range of pharmacological activities

Pharmacological activity Alkaloid

Analgesic & narcotics Morphine

CNS stimulant Caffeine & strychnine

Anti-tussive Codeine

Mydriatic Atropine

Anticancer Vincristine, vinblastine, taxol

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• Chemical classification:

Non-heterocyclic Heterocyclic

=typical alkaloids =Atypical alkaloids( Protoalkaloids)

14 major groups

according to ring structure

I. Alkaloids of the Pyridine nucleus:

classified according to building nucleus into:

Pyridine nucleus

only

Pyridine nucleus

+ another

nitrogenous ring

Tetrahydro-pyridine nucleus

N

H

Piperidine nucleus

N

Pyridone nucleus

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Volatile liquids

1) Pyridine alkaloids containing another nitrogenous ring:

e.g. Tobacco alkaloids

N

N

H

H

CH3N

N

H

-(-)nicotine (major)

nor-nicotineCH3

N

N

H

nicoteine

non-volatile liquid

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CH3N

N

H

Properties:

Nicotine

Colourless or pale yellow oily liquidair or light

brown

2 basic N atoms

form salts with acids

less basic

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Tests: nicotine + picric acid Crystals

Pharmacological actions & uses:

Little use in medicine due to high toxicity

In small doses respiratory stimulant

In larger doses respiratory depressant

Increases incidence of abortion

Main use : Insecticide & anthelmintic in veterinary medicine

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2 (Piperidine alkaloids:

e.g. alkaloids of :

a) Black pepper b) Conium

d) Pomogranate

a) Pepper alkaloids:

Occurrence: fruits of Piper species e.g. P. nigrum

Major alkaloid: piperine

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It is very weak basic No salt +acid

Colour tests +H2SO4 Red colour

c) Lobelia

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• insoluble in: H2O

• soluble in: CHCl3 & EtOH

• Piperine +alc KOHPiperidine + Piperic acid

Crystal testsalc. soln. + Wagner`s reag. blue crystals

Uses:

Mainly as condiment

Used in rubefacient preparations

Chronic toxicity:

Prologed use at high doses

loss of taste buds in tongue

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Little use in medicine

C- LOBELIA ALKALOIDSOccurrence: the dried aerial parts

of Lobelia inflata.(indian tobacoo)

Major alkaloid: Lobeline crystalline)

Uses:

-Asthma

-Chronic bronchitis

-Anti-smoking preparations

-Injection of lobeline hydrochloride is used in the resuscitation of newborn infants.

Caution: Toxic doses the herb has a paralytic effect

D- POMEGRANATE ALKALOID

Occurrence: the fruit rind, root bark and stem bark of Punica granata

Major alkaloid: pelltierine (liquid)

pelletierine tannate (mixture, solid)

Alkali decompose it to give free alkaloidsPomegranates have astringent properties because of the alkaloids (pelletierine tannate) present in the bark of the stems and roots and have been used for many years as an anthelmintic: removing tapeworms

II. Alkaloids of the Quinoline group

Most important → Cinchona alkaloids

Cinchona alkaloids

Present in the bark Cinchona species

- C. succirubra (red Cinchona) F. Rubiaceae

- Cinchona ledgeriana & C. calisaya (yellow Cinchona)

e.g. of alkaloids: two groups of stereoisomers:

Quinine (l) &

Quinidine (d)

Cinchonidine (l) &

Cinchonine (d)

>50%

N

CH2

CH2

N

CHHO

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R

CH CH2

R Alkaloid

H Cinchonine & cinchonidine

OCH3 Quinine & quinidine

Structure:

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Quinine:

Intensely bitter solid

Quinine (Cinchonidine epimer at C-9)Quinidine (Cinchonine epimer at C-9)

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Cinchonine & Cinchonidine are less soluble in H2O than quinine &

quinidine

Test:1) Fluorescence test: + dil H2SO4

Fluorescence

+ ve for quinine & quinidine

2) Thalleoquine test:

aq. soln of alkaloidal salt + Br2/H2O + NH4OH

Emerald green colour

Quinine (l) gives Quinidine (d) among other products when warmed with KOH in amyl alcohol

Uses:

anti-malarialused as

Quinidine used as

cardiac depressant (anti-arrythmic)

Quinine

as Quinine sulphate or other salts has febrifuge effect

(contra indicated in pregnancy as it causes abortion)

Cinchonine and Cinchonidine are used as anti-rheumatic

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Structure activity relationship:

For antimalarial activity (Quinine):

- Removal of vinyl group loss of activity

-Replacement of CHOH by:

- CHCl, CH2, CO decreases activity

N

N

CH2

CH2

CHHO

9

CH3O

CH CH2

Vinyl group

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III. Alkaloids of the Isoquinoline group

Ipecacuanha Opium

(Papaverine type)

N

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ISOQUINOLINE ALKALOIDS1- IPECACUANHA ALKALOIDSOccurrence:

Ipecac is the dried roots and rhizomes of Cephalis ipecacuanha (Brazilian ipecacuanha) or Cephalis acuminata (Cartagena or Panama ipecacuanha) Fam. Rubiaceae.

It contains several alkaloids (2 –2.5 %), mainly emetine (50- 70 % of total alkaloids), with cephaline and psychotrine.

N

MeO

RO

N

OMeOMe

HH

R = Me EmetineR = H Cephaline

N

MeO

HO

N

OMeOMe

H

Psychotrine

Emetine:

It is non phenolic and levorotatory.

It contains 2 basic nitrogens.

Cephaline:

It is phenolic and levorotatory.

It gives emetine on methylation with (CH3)2 SO4.

Psychotrine:

Occurs as yellow prisms.

It is phenolic and gives cephaline on reduction.

It gives emetine on reduction followed by methylation.

TESTS FOR IDENTIFICATION OF IPECA ALKALOIDS:

Alkaloidal solution in HCl + Ca hypochlorite orange color.

Emetine and cephaline + Froehd's reagent: dirty green color (the color with emetine fades by addition of HCl).

Psychotrine + Froehd's reagent: pale green color.

Cephaline and psychotrine + p-nitrodiazobenzene dye soluble in NaOH purple color.

Psychotrine + conc. H2SO4 + HNO3 cherry red color.

Emetine + Liebermann's reagent black color.

USES:

Emetine and cephaeline have antitumour and antiviral activity, but are too toxic for therapeutic use.

Emetine and psychotrine are mainly used as emetic drugs.

The crude drug is used as expectorant (due to its saponin content) .

Emetine HCl has an antiamoebic effect, and are used for the treatment of amoebic dysentry and Fasciola.

Ipeca alkaloids are diaphoretic, alone or in combination with opium (e.g. Dover's powder).