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
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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).