1. بسم الله الرحمن الرحيم
PHG 322 Pharmacogonsy II lecture 2 Presented by Assistant Prof. Dr. Ebtesam Alsheddi

2. Stability: hot dil. acids or conc. mineral acids may cause:
Generally alkaloids are decomposed by heat
except:
caffeine
sublimes without decomposition
Effect of Acids:
hot dil. acids or conc. mineral acids may cause:
Dehydration
O-demethylation
Next page !
e.g.
codeine
apoalkaloids
conc HCl
or HI
e.g.
morphine
apomorphine
morphine
+ CH3Cl or CH3I

3. Stability: (cont.) hot dil. acids or conc. mineral acids may cause:
Effect of Acids: (cont.)
hot dil. acids or conc. mineral acids may cause:
Hydrolysis of
- glucoalkaloids:
- ester alkaloids:
e.g.
solanine
e.g.
atropine

4. Effect of strong alkalies liberate most alkaloids from their salts
Stability: (cont.)
Effect of Alkalies:
Effect of
weak alkalies
Effect of strong alkalies
Effect of
hot dil. alkalies
liberate most alkaloids from their salts
form salts with alkaloids
containing carboxylic group
e.g
Narceine + NaHCO3
Na salt

5. hydrolysis of ester alkaloids
b) Effect of strong alkalies:
salt
(phenates)
phenolic alkaloid
+ aq. NaOH or KOH
c) Effect of hot dilute alkalies:
hydrolysis of ester alkaloids
cleavage of lactone ring
corresponding acid
e.g.
atropine
e.g. pilocarpine
Pilocarpic acid

6. Precipitation reactions precipitating reagent (contains heavy metals
Tests for identification:
include two types of reactions:
Precipitation reactions
Colour reactions
1) Precipitation reactions:
precipitating reagent
aqueous soln. of
alkaloidal salts +
(contains heavy metals
e.g. Hg, Cd, Bi, …)
Coloured ppts
(amorphous or crystalline)
N.B.
certain alkaloids do not react e.g. caffeine
false positive results are possible
most reagents precipitate: proteins, tannins, …

7. 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

8. + 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. HNO3
solid
(free base)
colour reagent +
characteristic
colour
(contain conc H2SO4
+ an oxidizing agent)
These tests are sensitive to micro amounts
used for colourimetric determination (quantitative)

9. - 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:
+ PDAB in conc H2SO4
blue colour

10. Pharmacological activity
N.B.
+ ve with:
- most alkaloids
Pharmacological activity:
wide range of pharmacological activities
Pharmacological activity
Alkaloid
Analgesic & narcotics
Morphine
Anti-tussive
Codeine
CNS stimulant
Caffeine & strychnine
Mydriatic
Atropine
Anticancer
Vincristine, vinblastine, taxol 10

11. Chemical classification:
Non-heterocyclic
Heterocyclic
= Atypical alkaloids
(Protoalkaloids)
= typical alkaloids
14 major groups
according to ring structure

12. Pyridine nucleus + another nitrogenous ring
Alkaloids of the Pyridine nucleus:
classified according to building nucleus into:
Pyridine nucleus only
Pyridine nucleus another nitrogenous ring
Tetrahydro-pyridine
nucleus
Piperidine
nucleus
Pyridone
nucleus 12

13. 1) Pyridine alkaloids containing another nitrogenous ring:
e.g. Tobacco alkaloids
non-volatile
liquid
Volatile
liquids
(-)-nicotine (major)
nicoteine
nor-nicotine

14. Nicotine Colour tests 2 basic N atoms form salts with acids
Properties:
air or light
Colourless or pale yellow oily liquid
brown
less basic
Colour tests
aq. soln +
PDAB
2 basic N atoms
rose red colour
form salts with acids
violet colour
gradually
Tests:
nicotine +
picric acid
Crystals

15. respiratory stimulant
Pharmacological actions & uses:
due to
high toxicity
Little use in medicine
In small doses
respiratory stimulant
In larger doses
respiratory depressant
Increases incidence of abortion
Main use:
Insecticide & anthelmintic in veterinary medicine

16. 2) Piperidine alkaloids:
e.g. alkaloids of:
a) Black pepper
b) Conium
c) Lobelia
d) Pomogranate
a) Pepper alkaloids:
Occurrence: fruits of Piper species e.g. P. nigrum
Major alkaloid: piperine
+ acid
It is very weak basic
No salt
Colour tests
+ H2SO4
Red colour

17. Crystal tests soluble in: CHCl3 & EtOH insoluble in: H2O Piperine
+ alc KOH
Piperidine +
Piperic acid
Crystal tests
alc. soln. + Wagner`s reag.
blue crystals

18. Uses: Chronic toxicity: Mainly as condiment
Little use in medicine
Used in rubefacient preparations
Chronic toxicity:
Prologed use at high doses
loss of taste buds in tongue

19. c- Lobelia alkaloids
Occurrence: the dried aerial parts of Lobelia inflata.(indian tobacoo) Major alkaloid: Lobeline crystalline)

20. 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

21. 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

22. 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)
Cinchonidine (l) & Cinchonine (d)
> 50%

23. Cinchonine & cinchonidine
Quinine (Cinchonidine epimer at C-9)
Quinidine (Cinchonine epimer at C-9)
Structure: R
Alkaloid H
Cinchonine & cinchonidine
OCH3
Quinine & quinidine
(few drops till yellow colour appears)
Quinine:
Intensely bitter solid

24. 1) Fluorescence test: + dil H2SO4 Fluorescence
Quinine (l) gives Quinidine (d) among other products when warmed with KOH in amyl alcohol
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

25. Uses: Quinine (contra indicated in pregnancy as it causes abortion)
as Quinine sulphate or other salts
used as
anti-malarial
has febrifuge effect
(contra indicated in pregnancy as it causes abortion)
used as
Quinidine
cardiac depressant (anti-arrythmic)
Cinchonine and Cinchonidine are used as anti-rheumatic

26. Structure activity relationship:
For antimalarial activity (Quinine):
- Removal of vinyl group
loss of activity
- Replacement of CHOH by:
- CHCl, CH2, CO
decreases activity
Vinyl group

27. III. Alkaloids of the Isoquinoline group
Ipecacuanha
Opium
(Papaverine type)

28. 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 ( % of total alkaloids), with cephaline and psychotrine.

29. It is non phenolic and levorotatory. It contains 2 basic nitrogens.
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.

30. 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.

31. 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).