ASSIGNMENT

NAME – IFTEKHAR ALAM

ROLL- 19P42
REG- 19109107011
SEMESTER- VI
COLLEGE- MIT, MUZAFFARPUR

signature of proff:
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 TOPIC :- CHEMISTRY, BIOGENESIS AND PHARMACOLOGICAL
ACTIVITY OF (A)EPHEDRIN (B)ERGOT ALKALOID (C) VINCA
ALKALOID

EPHEDRINE
 Ephedrine is a medication and stimulant .It is often used to prevent low blood
pressure during anesthesia. It has also been used for asthma , narcolepsy,
and obesity but is not the preferred treatment hydrochloride or sulfate salt.
 Ephedrine is a sympathomimetic amine and substituted amphetamine. It is
similar in molecular structure to phenylpropanolamine, methamphetamine,
and epinephrine (adrenaline). Chemically, it is an alkaloid with
a phenethylamine skeleton found in various plants in the
genus Ephedra (family Ephedraceae).
 It works mainly by increasing the activity of norepinephrine (noradrenaline)
on adrenergic receptors. It is most usually marketed as the hydrochloride or
sulfate salt.

CHEMISTRY :-

 Ephedrine exhibits optical isomerism and has two chiral centres, giving rise to
four stereoisomers. By convention, the pair of enantiomers with the
stereochemistry (1R,2S) and (1S,2R) is designated ephedrine, while the pair of
enantiomers with the stereochemistry (1R,2R) and (1S,2S) is called
pseudoephedrine.
 Ephedrine is a substituted amphetamine and a
structural methamphetamine analogue. It differs from methamphetamine only
by the presence of a hydroxyl group (—OH).The isomer which is marketed is (−)-
(1R,2S)-ephedrine.
BIOGENESIS :-
Ephedrine is formed by the union of a C6 – C1 unit and C2 unit. Phenylalanine is the originator of C6
– C1 moiety.

In the biogenesis of ephedrine, the phenylalanine is first converted to benzaldehyde and then to
benzoic acid.

Benzoic acid then combines with CH3CO group of pyruvic acid to form ephedrine with 1-
phenylpropane-1,2-dione and (S)-(-)-2-amino-1-phenylpropane-1-one serving as serving as
intermediates.

(S)-(-)-2-amino-1-phenylpropane-1-one then converts into (1S-2S)-(+)- norpseudoephedrine and

(1R,2S)-(-)-norephedrine.

Thus (1S-2S)-(+)-norpseudoephedrine converts to (1S-2S)-(+)-pseudoephedrine. Thus (1R,2S)-

(-)-norephedrine converts to (1R,2S)-(-)-ephedrine.
PHARMACOLOGICAL ACTIVITY : -
 Mechanism of action of ephedrine :- Ephedrine shows sympathomimtic effects. It
manly acts indirectly, but has some direct action as well on α and β receptors.
The principal mechanism of action relies on its indirect stimulation of the
adrenergic receptor system by increasing the activity of norepinephrine at the
postsynaptic α and β receptors. Ephedrine’s stimulation of α-1 receptors causes
constriction of veins and a rise in blood pressure, stimulation of β-1 adrenergic
receptors increase cardiac chronotropy and inotropy, stimulation of β-2
adrenergic receptors causes bronchodilation.

 Ephedrine is used as a bronchodilator in asthma and also in the treatment of 

allergic conditions like hay fever.

 As compared to adrenaline, the onset of action for ephedrine is slow. It is about

100 times less potent than adrenaline, but the action is prolonged, as it is not
hydrolyzed quickly by mono amino oxidase in the body. Hence it is longer acting
sympathomimetic drug.

 Ephedrine is also used to correct the low blood pressure conditions, because of
its peripheral contraction of arterioles. Hence, it is used for hypotension during
spinal anesthesia, or occasionally for postural hypotension

 . Ephedrine is also used as a nasal decongestant.

 ERGOT ALKALOID

 Ergot alkaloids comes under the class of indole alkaloids. Ergot is the dried
sclerotium of a fungus, Claviceps purpurea Tulasne, belonging to family
Clavicipitaceae or Hypocraceae, developed in the ovary of rye plant, Secale
cereale Linn, belonging to family, Graminae.

 Ergot alkaloids can be given as

 Ergot contains a large number of potent indole alkaloids, which are derived
from the lysergic acid. Lysergic acid is present in the peptide derivative form
and hence these alkaloids are also called as peptide alkaloids.

 Six pair of ergot alkaloids are broadly grouped into water soluble and water
insoluble categories. Each pair contains laevo-form which is medicinally active,
while dextro form is inert in action. The soluble pair contains (- )ergometrine
and its dextro part as ergometrinine. The water insoluble group is further
devided into Ergotamine and ergotoxine group.

(-) laevorotatory (+) dextrorotatory Molecar formula

alkaloids alkaloid

Water soluble: Ergometrinine C19H22O2N3

Ergometrine

Water insoluble: Ergotaminine C33H35O5N5

Ergotamine
Ergosinine C30H37O5N5
Ergosine
Ergocristinine C35H39O5N5
Ergocristine
Ergocryptinine C32H41O5N5
Ergocryptine
ergocorninine C31H39O5N5
Ergocornine
CHEMISTRY : -
 Ergot alkaloids are biosynthesized from the amino acid tryptophan.

 The indole alkaloids normally contain two nitrogens, out of which one is present
as indoline nitrogen and the other one is present in the position created by the
removal of two carbons from the para position of the indole ring.

 The molecular formula of ergot alkaloids are given in the table.

 Ergot alkaloids are the derivative of lysergic acid.

 The chemical structure of ergot alkaloids can be given as:

 Ergotamine is insoluble in water but very soluble in benzene, ethyl ether and
chloroform. It is very hygroscopic. Its molecular weight is 581.7 g.mol-1 . It
darkens and decomposes on exposure to air, light and heat. When heated to
decomposition it emits toxic fumes of nitrogen oxide.

 Ergometrine is a monocarboxylic acid amide that is lysergamide in which one

of the hydrogens attached to the amide nitrogen is substituted by a 1-
hydroxypropan2-yl group (S-configuration). Its molecular weight is 325.4 g.mol-
BIOGENESIS :The ergoline nucleus in ergot alkaloids are derived from tryptophan and
mevalonate.

 The indole alkaloids normally contain two nitrogens, out of which one is
present as indoline nitrogen and the other one is present in the position
created by the removal of two carbons from the para position of the indole ring.

 Lysergic acid serve as the intermediate in the synthesis of ergot alkaloids

 The building blocks for the lysergic acid skeleton of the ergot alkaloids are the 
amino acid L-tryptophan and the isoprene dimethylallyl diphosphate, the latter
deriving from 3R-mevalonic acid.

 Its biosynthesis in these fungi requires the amino acid L-tryptophan and
dimethylallyl pyrophosphate. These precursor compounds are the substrates for
the enzyme, tryptophan dimethylallyltransferase, catalyzing the first step in
ergot alkaloid biosynthesis, i.e., the prenylation of L-tryptophan. Further
reactions, involving methyltransferase and oxygenase enzymes, yield the
ergoline, lysergic acid. Lysergic acid (LA) is the substrate of lysergyl peptide
synthetase, a nonribosomal peptide synthetase, which covalently links LA to the
amino acids, L-alanine, L-proline, and L-phenylalanine. Enzyme-catalyzed or
spontaneous cyclizations, oxygenations/oxidations, and isomerizations at
selected residues precede, and give rise to, formation of ergotamine.

 Biogenesis of ergot alkaloids from lysergic acid can be given as:

PHARMACOLOGICAL ACTIVITY :
 Mechanism of action of ergot alkaloids :- Ergometrine and methyl ergometrine are
important drugs in obstetrics. Both the drug have the capacity to directly stimulate the
contractions of uterine and vascular smooth muscle by interacting with tryptaminergic,
dopaminergic, and alpha-adrenergic receptors. Small dose produce uterine contractions
with increased force and frequency and with normal resting muscle tone. Intermediate
dose produces more forceful and prolonged contractions with elevated resting muscle
tone, while large doses cause sustained contraction and tetany. Ergometrine
(Ergonovine) This amine ergot alkaloid has very weak agonistic and practically no
antagonistic action on α adrenergic receptors. Partial agonistic action on 5-HT2
receptors is most probably responsible for its powerful uterotonic effect.

 Ergotamine acts as a partial agonist and antagonist at α adrenergic and all subtypes of
5-HT1and 5-HT2 receptors, but does not interact with 5-HT3 or dopamine receptors.
Ergotamine tartrate is used as a specific analgesic in the treatment of migraine. It is
given along with caffeine.

 Ergot and it's alkaloids have many different uses. Nowadays it is not used as a whole but
the isolated alkaloids are used in therapeutics.

 Ergot and ergometrine maleate are used as oxytocic and sometimes used to enhance
the labour pain in delivery cases and also to prevent the postpartum hemorrhage.

 Ergotoxine methanesulphonates (mesylates) are used in geriatric patients.

 Lysergic acid diethylamide (LSD) is a semisynthetic derivative, and possesses

psychotomimetic action and hence used in psychiatry.

 Small dose of ergometrine and methyl ergometrine are used after delivery to control
bleeding and maintain uterine firmness. Methyl ergometrine is preferred over
ergometrine because it causes less hypertension.
 VINCA ALKALOIDS

Vinca alkaloids are a set of antimitotic and antimicrotubule alkaloid agents. It comes
under the class of indole alkalids. The indole alkaloids normally contain two nitrogens,
out of which one is present as indoline nitrogen and the other one is present in the
position created by the removal of two carbons from the para position of the indole ring.
Vinca alkaloids are obtained from the dried whole plant of Catharanthus roseus,
belonging to family Apocynaceae.

Vinca alkaloids can be given as:-

Vinca contains a large number of indole alkaloids. Out of them, about 20 dimeric
indoledihydroindole alkaloids possess oncolytic activity. Vincristine and vinblastine are
the most important dimeric indole-dihydroindole alkaloid of vinca. The other alkaloids
present in vinca are ajmalicine, lochnerine, serpentine and tetrahydroalstonine.

CHEMISTRY :
i. Vinblastine

 Molecular formula of vinblastine is C46H58N4O9.

 Molecular weight of vinblastine is 811.0 g.mol-1
 Vinblastine contains indole alkaloid part called catharanthine and dihydroindole part
called vindoline.
 It occurs as white to slightly yellow, amorphous or crystalline powder.
 It is practically insoluble in water, petroleum ether; soluble in alcohols, acetone, ethyl
acetate, chloroform.
 Its melting point is 267 OC
 Chemical structure of vinblastine can be given as:
ii. Vincristine

 Molecular formula of vincristine is C46H56N4O10.

 Molecular weight of vincristine is 825.0 g.mol-1
 It is a methyl ester, an acetate ester, a tertiary alcohol, a member of 
formamides, an organic heteropentacyclic compound, an organic
heterotetracyclic compound, a tertiary amino compound and a vinca alkaloid. It
is a conjugate base of a vincristine (2+). It derives from a hydride of a
vincaleukoblastine.
 Vincristine appears as a white crystalline solid
 Its Melting point is 218°C.
 Chemical structure of vinblastine can be given as:

Biogenesis :
 Vinca alkaloids are indole alkaloids. These alkaloids are synthesized from the
amino acid tryptophan.

 Vinblastine is produced by coupling of the indole alkaloids catharanthine and 

vindoline, both of which occur free in the plant. Formation of 3′,4′-
anhydrovinblastine from these monomers has been effected with peroxidase
isozymes isolated from C. roseus suspension cultures and with commercial
horseradish peroxidase.

  Vinblastine is produced by the condensation of catharanthine and vidoline.
 Vincristine is produced by the oxidation of N-methyl of vinblastine.
 Vincristine is structurally similar to vinblastine, but has a formyl group rather
than a methyl on the indole nitrogen in the vindoline-derived portion.

PHARMACOLOGICAL ACTIVITY:
Vinca alkaloids are used as antineoplastic agents.

Mechanism of action of vinca alkaloids:

 These are mitotic inhibitors which bind to microtubular protein-‘tubulin’

prevent its polymerization and assembly of microtubules, cause disruption of
mitotic spindle and interfere with cytoskeletal function. The chromosomes fail to
move apart during mitosis: metaphase arrest occurs. They are cell cycle specific
 and act in the mitotic phase. Vincristine and vinblastine, though closely related
chemically, have different spectrum of antitumour activity and toxicity.

 Vincristine acts by arresting mitosis at the metaphase. It is given intravenously in

the treatment of acute leukemia of children; some childhood leukemias are also
responded. In adults, hodgkin's diseases, reticulum cell sarcoma, lymphosarcoma
and myosarcoma have shown short remission.

 Vinblastine may act by arresting mitosis at metaphase or by interfering with

amino acid metabolism. It suppresses immune response and is mainly used in
the treatment of hodgkin's disease (a form of lymphoid cancer) and other
lymphomas and choriocarcinoma.

 Vinblastine is also used in the treatment of neuroblastoma, breast and testicular

carcinoma.

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