PHG 322 lecture 2

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‫بسم هللا الرحمن الرحيم‬
PHG 322
PHARMACOGONSY II
LECTURE 2
PRESENTED BY
ASSISTANT PROF. DR. EBTESAM ALSHEDDI
Stability:
 Generally alkaloids are decomposed by heat
except:
caffeine
sublimes without decomposition
 Effect of Acids:
 hot dil. acids or conc. mineral acids may cause:
O-demethylation
e.g. codeine
apoalkaloids
e.g. morphine
apomorphine
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conc
HCl
or HI
morphine
+ CH3Cl or CH3I
2
Dehydration
Stability: (cont.)
 Effect of Acids: (cont.)
 hot dil. acids or conc. mineral acids may cause:
Hydrolysis of
e.g. atropine
- glucoalkaloids:
e.g. solanine
3
- ester alkaloids:
Stability: (cont.)
Effect of Alkalies: 
Effect of
weak alkalies
Effect of strong
alkalies
liberate most alkaloids from their
salts
Effect of
hot dil. alkalies
form salts with alkaloids
containing carboxylic group
e.g
Narceine + NaHCO3
Na salt
b) Effect of strong alkalies:
phenolic alkaloid
salt
(phenates)
+ aq. NaOH or KOH
c) Effect of hot dilute alkalies:
hydrolysis of ester
alkaloids
e.g. atropine
cleavage of lactone ring
corresponding acid
e.g. pilocarpine
Pilocarpic acid
Tests for identification:
include two types of reactions:
Precipitation reactions
Colour reactions
1) Precipitation reactions:
aqueous soln. of
alkaloidal salts
precipitating reagent
+
(contains heavy metals
e.g. Hg, Cd, Bi, …)
Coloured ppts
N.B.
(amorphous or crystalline)
 certain alkaloids do not react e.g. caffeine
• false positive results are possible
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most reagents precipitate: proteins, tannins, …
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:
solid
(free base)
+
colour reagent
(contain conc H2SO4
+ an oxidizing agent)
characteristic
colour
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. HNO3
These tests are sensitive to micro amounts
used for colourimetric determination (quantitative)
- specific for one alkaloid or a group of related alkaloid:
1) Vitalis test for solanaceous alkaloids:
+ conc HNO3 & alc. KOH
violet colour
2) Van-Urks test for ergot alkaloids:
blue colour
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+ PDAB in conc H2SO4
Pharmacological activity:
wide range of pharmacological activities
Pharmacological activity
Alkaloid
Analgesic & narcotics
Morphine
Anti-tussive
Codeine
CNS stimulant
Mydriatic
Anticancer
Caffeine & strychnine
Atropine
Vincristine, vinblastine, taxol
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Chemical classification:•
= Atypical alkaloids
(Protoalkaloids)
Heterocyclic
= typical alkaloids
14 major groups
according to ring structure
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Non-heterocyclic
I. Alkaloids of the Pyridine nucleus:
classified according to building nucleus into:
Pyridine
nucleus
only
Pyridine
nucleus
+
another
nitrogenous
ring
Tetrahydropyridine
nucleus
N
Piperidine
nucleus
Pyridone
nucleus
N
H
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1) Pyridine alkaloids containing another
nitrogenous ring:
e.g. Tobacco alkaloids
H
H
N
(-)-nicotine
(major)
N
CH3
H
H
N
N
nor-nicotine
CH3
N
nicoteine
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N
Volatile
liquids
non-volatile
liquid
Nicotine
Properties:
 Colourless or pale yellow oily liquid
air or light
brown
H
N
less basic
N
CH3
2 basic N atoms
Tests:
nicotine picric
+
acid
Crystals
14
form salts with acids
Pharmacological actions & uses:
Little use in medicine
 In small doses
 In larger doses
due to
high toxicity
respiratory stimulant
respiratory depressant
 Increases incidence of abortion
Insecticide & anthelmintic in veterinary medicine
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Main use: 
2) Piperidine alkaloids:
e.g. alkaloids of: 
a) Black pepper
c) Lobelia
b) Conium
d) Pomogranate
a) Pepper alkaloids:
 Occurrence: fruits of Piper species e.g. P. nigrum
Major alkaloid: piperine 
+ acid
Colour tests+ H2SO4
No salt
Red
colour
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 It is very weak basic
soluble in:•
CHCl3 & EtOH
insoluble in:•
Piperine •
H2O
+ alc KOH
Piperidine +
Piperic acid
Crystal tests
blue crystals
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alc. soln. + Wagner`s reag.
Uses:
 Mainly as condiment
 Used in rubefacient preparations
Little use in medicine
Chronic toxicity:
 Prologed use at high doses
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loss of taste buds in tongue
C- LOBELIA ALKALOIDS
Occurrence: 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 alkaloids
Pomegranates 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
- Cinchona ledgeriana & C.
calisaya (yellow Cinchona)
- C. succirubra (red
Cinchona) F.
Rubiaceae
e.g. of alkaloids: two groups of stereoisomers:
Quinine (l) &
Quinidine (d)
> 50%
Cinchonidine (l) &
Cinchonine (d)
Quinine (Cinchonidine epimer at C-9)
Quinidine (Cinchonine epimer at C-9)
Structure:
CH
CH2
CH2
CH2
9
HO H C
N
R
Alkaloid
H
Cinchonine &
cinchonidine
OCH3
Quinine &
quinidine
R
N
Quinine:
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 Intensely bitter solid
Quinine (l) gives
amyl alcohol
Cinchonine &
quinidine
Quinidine (d) among other products when warmed with KOH in
Cinchonidine are less soluble in H2O than quinine &
Test:
1) Fluorescence test: + dil H2SO4
Fluorescence
+ ve for quinine & quinidine
2) Thalleoquine test:
aq. soln of alkaloidal salt + Br2/H2O
+ NH4OH
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Emerald green colour
Uses:
 Quinine
used as
as Quinine sulphate or other salts
anti-malarial
has febrifuge effect
(contra indicated in pregnancy as it causes abortion)
 Quinidine
used as
cardiac depressant (anti-arrythmic)
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 Cinchonine and Cinchonidine are used as anti-rheumatic
Structure activity relationship:
 For antimalarial activity (Quinine):
loss of activity
- Removal of vinyl group
- Replacement of CHOH by:
- CHCl, CH2, CO
decreases activity
Vinyl group
CH
CH2
CH2
CH2
9
HO H C
N
N
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CH3O
III. Alkaloids of the Isoquinoline group
N
Opium
(Papaverine type)
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Ipecacuanha
ISOQUINOLINE ALKALOIDS
1- IPECACUANHA ALKALOIDS
Occurrence:
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.
MeO
RO
MeO
OMe
N
H
OMe
H
N
R = Me Emetine
R=H
Cephaline
HO
OMe
OMe
N
H
N
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).

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