By : Vishal Sachan

B.Pharma (4th yr)

1
 Definition: the term “alkaloid”
(alkali-like) is commonly used to
designate basic heterocyclic,
nitrogenous compounds of plant
origin that are physiologically active.

2
 Basicity: Some alkaloids are not basic
e.g. Colchicine, Piperine, Quaternary
alkaloids.
 Nitrogen: The nitrogen in some alkaloids
is not in a heterocyclic ring e.g.
Ephedrine, Colchicine, Mescaline.
 Plant Origine: Some alkaloids are derived
from Bacteria, Fungi, Insects, Frogs,
Animals.

3
 True (Typical) alkaloids that are derived
from amino acids and have nitrogen in a
heterocyclic ring. e.g Atropine
 Protoalkaloids that are derived from
amino acids and do not have nitrogen in
a heterocyclic ring. e.g Ephedrine
 Pseudo alkaloids that are not derived
from amino acids but have nitrogen in a
heterocyclic ring. e.g Caffeine
 False alkaloids are non alkaloids give
false positive reaction with alkaloidal
reagents.

4
 Biogenetic.
Based on the biogenetic pathway that form the
alkaloids.

 Botanical Source.
According to the plant source of alkaloids.

 Type of Amines.
Primary, Secondary, Tertiary alkaloids.

 Basic Chemical Skeleton

5
 Phenylalkylamines:
e.g. Ephedrine CH2 CH CH3

NH2

 Pyridine and piperidine

e.g. lobeline, nicotine

N N
H
 Tropane
e.g. Atropine.
NCH3 OH
 Indole
e.g.ergometrine
N
H

 Imidazole N
e.g. pilocarpine

N
 Purine
H
e.g. caffeine 6 7
1 N 5 N
8
2
N 4 N
9
3
Purine
 Quinoline
e.g.quinine and
quinidine
N

 Isoquinoline
e.g. papaverine
N

 Phenantheren
e.g. Morphine
 Quinoline
e.g.quinine and
quinidine
N

 Isoquinoline
e.g. papaverine
N

 Phenantheren
e.g. Morphine
 Steroidal
e.g. Solanum and
Veratrum alkaloids

 Terpenoid
e.g. Taxol
 Extraction and purification
Method I:
The powder is treated with alkalis to liberates the free
bases that can then be extracted with water immiscible
organic solvents.

Method II:
The powdered material is extracted with water or
aqueous alcohol containing dilute acid. Alkaloids are
extracted as their salts together with accompanying
soluble impurities.

Method III:
The powder is extracted with water soluble organic
solvents such as MeOH or EtOH which are good solvents
for both salts and free bases.
11
 Plant material and solvent

Organic solvent dissove Alkaloids

Organic solvent dissove Impurities
Extract

Concentration Acidification

Alkalinization

Acidified Extract (Alk. as salts)

Alkaline aqueous layer
 Repeated Acid-Base procedures:
Render extract Acidic, extract with organic
solvent (dissolve non alkaloidal impurities),
Alkalinize and extract again with organic
solvents (Dissolve Alkaloids).
 Precipitation with alkaloidal precipitating
agent.
 Convert to crystalline salts.

13
 Role of SHIKIMIC ACID
PATHWAY in Alkaloid synthesis

14
Shikimic acid pathway is the part of Phytochemistry i.e
study ofchemicals derived In plant( secnd. Metabolites).

Q – 1 Diff. b/w Phytochemistry & Biochemistry ?

Q- 2 What are primary and secondory metabolites?

Starting material for Shikimic acid pathway are-

1-Phosphoenolpyruate ,
2- Erythrose-4-phosphate.
Both are ultimately the product of glucose.

15
Shikimic acid is a precursor for-
a)Aromatic amino acids-
Phenylalanine, Tyrosine,
b)Indole ,Indole derivative, aromatic
amino acid tryptophan,
c)Many alkaloid & other aromatic
metabolites,
d)Tannins, flavonoids & lignin.

16
 THE SHIKIMIC ACID PATHWAY
This pathway (unique to plants) leads to the formation of the
aromatic amino acids phenylalanine and tyrosine and to the
formation of many other phenyl-C3 compounds.

C C C Phenylpropanoids
Phenyl-C3

Cleavage of the C3 side chain leads to many phenyl-C1 compounds.

C C C C

Phenyl-C1
17
 GLUCOSE ORIGINS OF THE
pentose SHIKIMIC ACID
phosphate
pathway glycolysis
PATHWAY

Erythrose-4-phosphate PEP
Phosphoenol pyruvate

The pentose phosphate

pathway is one that
Acetyl-CoA converts glucose into
sugars of different sizes
Shikimic Acid (different numbers of C)
by acyl interchanges.
Erythrose is a 4-carbon
sugar.
18
 FORMATION OF SHIKIMIC ACID

H phosphoenol pyruvate
COOH
O O C
H O COOH
HO P O C CH2
B: H
O CH2
HO OH
H
O
H H+ H
HO O HO P O CH2 HO
H
O
PO CH2 HO H

erythrose-4-phosphate

H+ H+
COOH
HO
COOH COOH COOH O C
CH2
NADPH H
H2C H
OH
HO OH O OH O OH
OH HO H
OH OH H O

shikimic acid
19
 FORMATION OF CHORISMIC ACID
hydrolysis
of PEP
COOH COOH

ATP

HO OH P O OH CH3
OH OH C O
COOH H+
shikimic acid pyruvic acid

nucleophilic
addition to C=O

COOH COOH :B COOH

- H3PO4 H - H2O
CH2 CH2 CH3
O C P O O C P O O C OH
OH COOH OH COOH OH COOH

chorismic acid

20
 COOH
O
CH2
OH O
O C
OH COOH NH2
NH2
N
chorismic acid H
Anthranillic Acid Tryptophan

Alkaloids containing
Indole
Ring ex- Vincristine ,
vinblastin,
Resrepine

21
 PREPHENIC ACID
chorismic acid
HOOC
COOH
C
Claisen Type CH2
O C CH Rearrangement
O
2 C O H
H
C OH H O

HO O
OH prephenic acid
pseudoaxial conformation

Prephenic acid can be converted to phenylpyruvic acid

or to 4-hydroxyphenylpyruvic acid:
O
HOOC CH2 C
COOH
NADPH NADP+
p-hydroxy- phenypyruvic
phenylpyruvic -H+ - CO2 -H- -H+ - CO2 -OH acid
H OH
acid

tyrosine phenylalanine
22
 CLAISEN REARRANGEMENT
A THERMAL REARRANGEMENT

CHR
CHR CHR
H
O
heat O H+ OH

enolization

an allyl ether an allyl phenol

23
PREPHENIC ACID TO PHENYLALANINE
HOOC
C
CH2 :B-Enz O
O
C O H CH2 C COOH

H O
- CO2
- H2O phenylpyruvic acid
OH prephenic acid

H+ transamination

CH2 CH COOH
Ephedrine, NH2
Mescaline

phenylalanine

24
 PREPHENIC ACID TO TYROSINE
HOOC
C
O CH2 :B-Enz O
C O H CH2 C COOH

H O
- CO2 HO 4-hydroxyphenyl-
NAD+
OH prephenic acid pyruvic acid

transamination
hydride transfer
to NAD+

CH2 CH COOH
NH2
Codeine Thebaine
HO
tyrosine

Morphine
25
 O Papaverine
O
N (against spasms)
O

NH2 O

CO2H NH HO O
NH O N
HO OH HO
OH O O
O
Tyr
HO OH OH O
OH
Norlaudanosoline
O

CH3 CH3 CH3

N N N

H3C O O O CH3 H3C O O OH HO O OH

Thebaine codeine Morfin

26
PHENYLALANINE AND TYROSINE COME FROM
A COMMON SOURCE AND ARE NOT CONVERTED

PREPHENIC ACID

phenylpyruvic acid 4-hydroxyphenylpyruvic acid

CH2 CH COOH CH2 CH COOH

NH2 X NH2
HO

phenylalanine tyrosine

Although most plants could convert phenylalanine to tyrosine

using hydroxylases, this conversion is a minor pathway. Most
plants make enough tyrosine without converting phenylalanine.
27
A PRELIMINARY OVERVIEW

28
 Shikimate SHIKIMIC ACID
Pathways
CHORISMIC ACID Anthranillic acid

PREPHENIC
ACID Tryptophan

TYROSINE Alkaloid having

Indole ring like
Vincristine,
PHENYLALANINE Vinblastine,
Reserpine etc

Thebaine , Codeine,
Morphine Ephedrine, Mescaline
29
30
31