content HETEROCYCLIC ALKALOIDS Piperidine Alkaloids (Pepper, Conium, Lobelia and Pomegranate alkaloids) Pyridone alkaloids (Ricinine) Pyridine Alkaloids (Trigonelline, Tobacco and Areca nut alkaloids)

1. HETEROCYCLIC ALKALOIDS
PIPERIDINE AND PYRIDINE
Assoc. Prof. Dr. Mostafa Mahmoud Hegazy

2.  content
 HETEROCYCLIC ALKALOIDS
 Piperidine Alkaloids (Pepper, Conium, Lobelia and Pomegranate alkaloids)
 Pyridone alkaloids (Ricinine)
 Pyridine Alkaloids (Trigonelline, Tobacco and Areca nut alkaloids)

4. * Piperidine Nucleus can be obtained by hydrogenation of pyridine using Nickel
as catalyst.
* Piperidine Alkaloids are biosynthesized from L-Lysine amino acid.
Piperidine
N
Pyridine
N
H
Nickel
Piperidine Alkaloids
L-Lysine
H2N
H2N O
OH

5. ◘ Pepper alkaloids.
◘ Conium alkaloids.
◘ Lobelia alkaloids.
◘ Pomegranate alkaloids.
Piperidine Alkaloids
Piperidine
NH
e.g.

6. Occurrence
Fruits of Piper nigrum, (Fam. Piperaceae)
Pepper alkaloids
N
CH3
O
O
O
Piperine

7. ◘ Piperine is a weak basic alkaloid.
◘ It does not form stable salts.
◘ It is decomposed easily with alcoholic
KOH to yield piperidine and piperic acid.
Color test:
Piperine + H2SO4  red color. N
CH3
O
O
O
Piperine

8. Uses
◘ increases bioavailability of curcumin
◘ Condiment
◘ Tonic and rubefacient.
◘ In traditional medicine, used as
stimulant, carminative and tonic.

9. Occurrence: The hemlock fruits, Conium
maculatum, (Fam. Umbelliferae)
Conium alkaloids
N N
H
(+)Coniine -Coniceine

10. Properties
Coniine and  -Coniceine
are non-oxygenated, volatile, liquid alkaloids
Coniine is a colorless oily liquid,
with mice-like odor and a burning taste.
Violet or blue color
Color test:
Coniine + sodium nitroprusside solution Red color
CH3
O
N N
H
(+)Coniine -Coniceine

11. Uses
◘ Coniine is used as a local analgesic,
mostly in external preparations, due to
its high toxicity. It is used as an ointment
for treatment of hemorrhoids and anal
fissures.
Coniine is very poisonous,
lethal dose 120-300 mg, death may occur
after ½ hr (or may prolonged to 3 –12 hrs)

12. Lobelia alkaloids
Dried aerial parts of Lobelia inflata (Fam. Campanulaceae)
◘ These alkaloids contain piperidine rings with alternative C6C2 side-chains derived from
phenylalanine via cinnamic acid.
N
O O
CH3
N
O
CH3
OH
N
CH3
OH
OH
Lobelanine
(-)-Lobeline Lobelanidine
Partial
reduction
Full
reduction

13. Lobeline
◘ a tertiary base alkaloid.
◘ It is a keto-alcohol.
◘ It forms a monooxime monoester.
◘ Lobeline HCl salt is soluble in CHCl3
Lobelanine Is a diketonic compound,
therefore it forms a dioxime.
Lobelanidine It does not form any oxime
(ketonic group absent).
Properties:
N
O O
CH3
N
O
CH3
OH
N
CH3
OH
OH
Lobelanine
(-)-Lobeline Lobelanidine
Partial
reduction
Full
reduction

14. Tests for identification of lobeline
Lobeline gives with:
◘ Marqui`s reagent  red violet color
◘ Erdmann`s reagent  faint green color
◘ Froehd's reagent  rose red color  blue
◘ Rosette crystals with potassium cyanide or sod. Carbonate
solution.

15. Uses of Lobelia
◘ Respiratory stimulant.
◘ Expectorant.
◘ Relieve asthma.
◘ Lobeline sulfate was formerly incorporated in tablets or
lozenges, that were intended to aid in breaking the tobacco
habit (smoking deterrents).

16. Pomegranate alkaloids:
◘ The fruit rind as well as the root and stem
barks of Pomegranate [Punica granatum,
Fam. Punicaceae].
Piperidine Alkaloids

17. Properties:

18. Powdered bark - Maceration with Ca(OH)2
(liberation of bases & precipitation of tannins)
- Extraction with CHCl3
(Alkaloidal tannates)
CHCl3 extract
(Alkaloidal bases)
- Extract with HCl Acidic aqueous layer
(Alkaloidal HCl) - Alkalinization with Na2CO3
(liberation of weak bases)
- Extraction with CHCl3
Alkaline aqueous layer
(Hydrochlorides of strong bases)
Pelletierine HCl & Isopelletierine HCl
- Alkalinization with NaOH
- Extraction with CHCl3
CHCl3 extract
(Strong alkaloidal bases)
Pelletierine & Isopelletierine
- Acidification with dil. H2SO4
- Concentration & Drying in a dessicator
Isopelletierine sulphate (Oily)
E
xtractio
nan
dS
ep
aratio
no
fP
o
m
eg
ran
ateA
lk
alo
id
s
CHCl3 layer
(Weak alkaloidal bases)
Methylpelletierine & Pseudopelletierine
- Evaporation,
- Extraction with ether
- Concentration
Crystals Mother Liquor
Pseudopelletierine
- Evaporation
Methylpelletierine
(Oily liquid)
Pelletierine sulphate (Crystals)

19. Uses
◘ Pelletierine is highly toxic to tape worms
◘ Anthelmintic against pork tape worms and Ascaris.
◘ It is also used as a Taenifuge.

20. Pyridone alkaloids
Ricinine
Occurrence:
In the seeds of Castor, Ricinus communis L.
(Fam. Euphorbiaceae)
It possesses no basic character and
therefore does not form salts with acids.
N
OMe
C
O
CH3
N
Ricinine

21. Color tests:
Ricinine decolorizes a solution of KMnO4.
Ricinine + conc. HNO3 in a dish on a water bath Yellow residue
NH4OH
Red
Ricinine + Wagner’s reagent PPt.
Ricinine + Mayer's reagent No PPt.

22. Toxicity of Ricinine
Ingestion of Ricinine causes
Vomiting Hemorrhagic Gastroenteritis
Hepatic and Renal damage
Convulsions Coma Hypotension
Respiratory depression Death

23. Pyridine Alkaloids

24. Pyridine Alkaloids
Trigonelline
Fenugreek (Fam. Leguminoseae)
◘ Soluble in water.
◘ It is derived from nicotinic acid,
which is biosynthesized from
L-tryptophane amino acid.
Trigonelline
COO
N
CH3
Actions:
Hypoglycemic in diabetic patients.

25. NH2
N
H
O
OH
Nicotinic acid
N
O
HO
Tryptophane

26. Tobacco Alkaloids
◘ Tobacco is the cured and dried
leaves of Nicotiana tabacum
(Fam. Solanaceae).
Pyridine alkaloids Containing another
Nitrogenous ring

27. Tobacco Alkaloids

28. * Nicotine is a pale yellow or colorless oily liquid, turns brown on
exposure to air or light.
* Nicotine is an example of tertiary amine alkaloid.
* It is volatile with steam.
* It possesses two basic nitrogen atoms.
* Nicotine is biosynthesized from nicotinic acid and proline
(derived from L-ornithine).

29. Color Tests:
1) Aqueous solution of Nicotine + p- dimethyl amino
benzaldehyde  Rose red  Violet color.
2) Aqueous solution of Nicotine + Vanillin/ HCl  Red color.

30. Powdered Leaves
* Acidification with H2O/ HCl
* Conc.
Distilled fraction
Ex traction a nd separation of Tobacco alk a loids
Extract
* Alkalinization with NaOH
* Steam distillation
Undistilled fraction
Volatile alkaloids
* Extract with ether
* Evaporate the ether extract
* Treatment with HCl & NaNO2 on cold
(Nicotine, Nor-nicotine & Anabasine)
Oily layer Aqueous layer
Nitroso derivative of
Anabasine & Nor-nicotine
Nicotine HCl
* Extract with benzene
* Evaporattion
Residue
Non-volatile alkaloids
(Nicoteine & Nicotelline
* Solubilization with ether
* Conc.
Mother liquor Crystals
Nicoteine (Liq.) Nicotelline (Solid)

31. Oily layer Aqueous layer
Nitroso derivative of
Anabasine & Nor-nicotine
Nicotine HCl
* Heating with HCl
* Alkalinization with NaOH
* Extraction with ether
* Evaporation
Residue
Anabasine & Nor-nicotine
(Liq 2ary
amines)
* Fractional distillation
under reduced pressure
Anabasine Nor-nicotine
* Alkalinization with NaOH
* Extraction with ether
* Evaporation
Nicotine
(Liq 3ary
amine)

32. Uses:
◘ Small doses of nicotine stimulate respiratory
processes, but larger doses cause inhibition in
all sympathetic and parasympathetic ganglia.
Death results from respiratory paralysis.
◘ Nicotine and Anabasine are used as
insecticides in form of sulfate salts.

33. * Nicotine can be used commercially to produce
one of vitamin B-complex named Nicotinic acid
or Niacin (Vitamin B3) used to prevent Pellagra.
NICOTINE
CH3
N
N
H
Oxidation
Nicotinic acid
(Niacin or Vitamin B3)
COOH
N

34. Occurrence
Areca nut (or Betel nut) is the seed of
Areca catechu Linne (Fam. Palmae or
Arecaceae).
Areca nut alkaloids
Tetrahydropyridine alkaloids
N
Tetrahydropyridine

35. N
COOR2
R1
Arecoline (arecaidine methyl ester)
Arecaidine (N-methyl guvacine)
Guvacine (tetrahydro nicotinic acid)
Guvacoline (guvacine methyl ester)
Arecoline
Arecaidine
Guvacine
Guvacoline
CH3 CH3
CH3 H
H H
H CH3
Name R1 R2
Areca nut alkaloids
Arecoline is the most physiologically active

36. Tests for identification
Arecoline + potassium ferricyanide 
blue color.
Arecoline + potassium ferrocyanide 
Green color
Uses
Anthelmintic in veterinary medicine