1. NON-HETEROCYCLIC ALKALOIDS
ASSOC. PROF. DR. MOSTAFA MAHMOUD HEGAZY

2.  content
 Definition of Non-Heterocyclic Alkaloids
 Ephedra alkaloids
 Khat alkaloids
 Mescaline
 Capsicum alkaloids
 Alkaloids of the Tropolone skeleton

3.  Non-Heterocyclic Alkaloids
 AKA (Alkaloids with Exocyclic Nitrogen or Proto
alkaloids or Phenyl alkylamine alkaloids)
 Def.: This group of alkaloids have the nitrogen atom
located in an amino group and is not a member of a
heterocyclic ring i.e. alkaloids characterized by the
absence of heterocyclic ring in their molecules.

4.  Many are simple derivatives of
Phenyl ethyl amine and as such, are
derived from the common amino
acids Phenylalanine or Tyrosine.
 They are Sympathomimetic drugs
(as they rise the blood pressure).
* They includes the alkaloids of:
2) Khat alkaloids
3) Capsicum alkaloids
1) Ephedra alkaloids
4) Colchicum alkaloids
Phenylethylamine
NH2
Phenylalanine
H2N
O
OH
Tyrosine
H2N
O
OH
HO

5. 1- Ephedra alkaloids
* Present in the arial parts of several Ephedra species,
especially Ephedra sinica (Family Ephedraceae).
* Ephedrine is the main alkaloid of Epherda sinica.
* Epherdine is α-OH-β-methyl-aminopropyl-benzene.
* Ephedine is structurally related to the animal
hormone Adrenaline (or Epinephrine) and has similar
pharmacological actions.

6.  Properties of Ephedrine
 The free base is volatile with steam (it can be determined
in the drug and when present associated with other non-
volatile alkaloids.
 It decomposes on exposure to light.
 It is a strong base, soluble in water.
 Its alcoholic solution is levorotatory.
 Chloroform is not recommended for the extraction of
ephedrine (Why?).

7. Ephedrine in aged CHCl3  Ephedrine HCl
with release of the toxic phosgene.

8. Preparation of Ephedrine
1) Steam distillation (since the free base is volatile).
2) Extraction by using benzene as solvent instead of chloroform.
3) Shaking with dilute HCl, which extracts both ephedrine and pseudo-ephedrine
as their hydrochloride salts followed by separation of the mixture.

9. 4- Separation of ephedrine from the less active pseudo-
ephedrine
 Ephedrine is more soluble in water than pseudo-
ephedrine .
 Ephedrine oxalate is less soluble in water than
pseudo-ephedrine oxalate.
 Ephedrine HCl is less soluble in CHCl3 and alcohol
than pseudo-ephedrine HCl.

10. Special chemical tests for ephedrine:

11. 2- Ephedrine + crystal of potassium
ferricyanide + drops of water in porcelain
dish. Heat on water bath  odor of
benzaldehyde (bitter almond odor ?).
3- Dragendorff’s reagent  red-brown
branching needles and blades form rather
rapidly upon the addition of this reagent.

12. CHO
CH3CH2NO2 K2CO3
Nitroethane
Benzaldehyde
+ CHOHCHCH3
NO2
Reduction
CHOHCHCH3
NH2
Norephedrine
Methylation
CHOHCHCH3
NHCH3
Ephedrine
Chemical synthesis of Ephedrine

13.  Activities of Ephedrine
 Ephedrine's basic pharmacological action
resembles epinephrine (adrenaline), but is
considerably less active.
 Ephedrine can also be absorbed orally, unlike
epinephrine.
 Ephedrine is an indirectly acting as
Sympathomimetic amine.
 Ephedrine also has a longer duration of action
and more pronounced effects on the brain and
central nervous system.

14.  Activities of Ephedrine
 These CNS effects resemble
amphetamines, but are less potent.
 Ephedrine increases blood pressure, and
heart rate.
 Ephedra does not suppress appetite, but it
will promote weight loss by increasing the
metabolic rate of adipose tissue.

15.  Uses of Ephedrine
 It is a potent nasal decongestant due to its
vasoconstrictor action on blood capillaries of
mucous membranes.
 It used in cough mixtures to relieve asthma and
hay fever due to its bronchodilator activity
(relaxes bronchial and uterine muscle).

16. 2- Khat alkaloids
 Khat or “ Abyssinian tea” consists of the fresh leaves
of Catha Edulis (Family Celastraceae). A small tree
cultivated in Ethiopia, East and South Africa, and the
Yemen. The leaves are chewed for a stimulant effect.
 The major alkaloids are Cathine (nor-pseudo
ephedrine) and (-)-Cathinone. They are primary
amines derived from Phenylalanine amino acid.
 For maximum effects, the leaves must be fresh.

18.  Biological activities
 Dried leaves contain up to 1% cathine ((+)-
norpseudoephedrine, but young fresh
leaves contain (−)-cathinone as the
principal CNS stimulant.
 Cathinone has similar pharmacological
properties as the synthetic CNS stimulant
(+)-amfetamine.
 Both compounds act by inducing release
of catecholamines.

19. MeO
MeO
NH2
OMe
Mescaline
 Mescaline
(3, 4, 5-trimethoxy–phenylethylamine)
 dried tops of the Cactus lophophora
(Fam. Cactaceae)
 Mescaline is a hallucinogenic alkaloid,
derived from phenylalanine amino
acid

20. Tests for identification
Color tests:
1) Mescaline with Marqui's reagent  orange color.
2) Mescaline with ammonium molybdate  green color that turns to blue.
Crystal tests:
1) Mescaline gives orange needles with gold chloride.
2) Mescaline gives yellow needles with platinum chloride.

21. uses
 Mescaline is regarded as the first of a series
of hallucinogens or psychomimetics, in a
dose of 400-700 mg by injection.
 Habituation and addiction do not result
from repeated use of mescaline, so it is not
regarded as a narcotic drug.

22. 3- Capsicum alkaloids (Capsaicin) suffix ???
 The amide capsaicin constitutes the powerfully
pungent principle isolated from chilli peppers
(Capsicum mnimum; Solanaceae).
 Capsaicin is a phenolic amide alkaloid or vanillyl
amide of Isodecenoic acid.
 Capsaicin imparts a pungent taste to water, even
when diluted. The pungency is destroyed by
oxidation with KMnO4.
N
H
O
CH3
CH3
H3CO
HO Capsaicin

23. Does it considered as an alkaloid?
Capsaicin does not possess basic characters, due
to the presence of nitrogen in an amide group
and phenolic . Therefore can be extracted with
ether from acid medium.
Chemical Tests:
Capsaicin in alcohol
FeCl3
Green color (due to phenolic character).
1)
Capsaicin Solution in Conc H2SO4 + Sucrose Violet color
2)

24. Uses:
* Capsaicin is used as a counter-irritant in medicated
plasters to relief Rheumatism and Lumbago as a
topical analgesic
* it is also used as counter irritant in neuralgia caused
by herpes infections and hair falling preparations.

25. * The aromatic portion of capsaicin is derived from phenylalanine through ferulic
acid and vanillin, this aldehyde being the substrate for transamination to give
vanillylamine.
* The acid portion of the amide structure is of polyketide origin, with a branched-
chain fatty acyl-CoA being produced by chain extension of Isodecenoyl-CoA. This
starter unit is valine derived.

26. Alkaloids of the Tropolone skeleton
Colchicum autumnale (Liliaceae)
Colchicine no longer has its nitrogen atom
in a ring system.
Colchicine
O
OCH3
H3CO
H3CO
OCH3
H
N
H CH3
O

27. ● Colchicine, being an N-acetyl derivative (amide), is
a very weak base and does not form well-defined salts.
● It occurs as yellow needles
Isolation:
● Defatted seeds are extracted with CHCl3.
● Concentrate CHCl3 extract; add alcohol until
whitish precipitate is formed.
● Cool, crystallize colchicine and recrystallize from
ethyl acetate.

28. * Activities: anti-inflammatory and tubulin depolymerization

29. * Effect on Cardiovascular system

30. * Effect on Cardiovascular system

31. * Colchicine Used in the treatment of gout, a painful condition in which
impaired purine metabolism leads to a build-up of uric acid crystals in the joints
It appears to act primarily as an anti-inflammatory agent, and does not itself
affect uric acid metabolism
Colchicine is also used to treat a rare condition called familial Mediterranean
fever and thalassemia.
* Potential anticancer agents.
Colchicine binds to tubulin in the mitotic spindle, preventing polymerization
and assembly into microtubules as do vincristine

32. Tests for identification
1) Colchicine + mineral acids 
yellow color.
2) Colchicine + conc. HNO3 
dirty green color  brown
yellow.