Finnall Revvisioon

A aloidds
Alka

INTRODUCTION OF ALKALOIDS
1 Definition:Basic nitrogenous Cpds of biological origin having pharmaceutical activity

2 Restrictions To Definition :1-All alkaloids are nitrogenous Cpds ,but not all nitrogenous Cpds are alkaloids
2-Some alkaloids are found in animals and fungi Ergot & almost all alkaloids are
synthesized
3-Most alkaloids are basic but some are acidic or amphoteric Colchicine
3 Toxicity Of Alkaloids 1-Ergot alkaloids: Cause epidemic poisoning Duo to feeding on rye bread
contaminated with the Fungus
2-Curare extract Tubocurarine Alk. Used as arrow poisoning in hunting & wars
3-Hemlock Coniine Alk. In socrats execution
4-Belladonna Atropine Alk. In murdering purpose
5-Egyption henbane Hyoscyamine Alk. For suicidal purpose

4 Classification Of Alkaloids .A-Pharmacological Action

B-Chemical Structure
C-Hegnauers Classification
D-Biochemical Origin
E-Taxonomical Origin
1

B-Acc. To Chemical Structure

Heterocyclic

Non Heterocyclic

Typical Alkaloids

Atypical Alkaloids

Sub classified into different gps. Acc. To

Called Proto Alk. Or Biological amines

their ring structure

C-Acc. To Hegnauers Classification

Based on the type of nitrogen and biological origin

Type Of Alkaloid

Precursor

Type Of N

True Alkaloid

Amino Acid

Heterocyclic

Proto Alkaloid

Amino Acid

Non - Heterocyclic

Pseudo Alkaloid

Non - Amino Acid

Heterocyclic

5 Distribution Of Alkaloids : Major Source of alkaloids are flowering plants Angiosperms but recently
they are discovered in animals and Fungi and marine plants
1) True Alkaloids : Rare in lower plants

e.g) Ergot alkaloids from fungi

2) Alkaloids of pteridophytes and gymnosperms are used in medicine

e.g) Ephedra & Taxus Alk.
a) Some free from alkaloids e.g) Salicales ,Cucurbites & Oleales
b) Some rich in alkaloids e.g) Monocot Liliaceae , Dicot Solanaceae
3) Same Alkaloids may be present in different genera of the same family
e.g) Hyoscyamine in Atropa ,Datura, Hyoscyamus which belong to family Solanaceae
4) Rarely the same alkaloid may be present in unrelated species Nicotine because its
simple biosynthesis
5) Alkaloids may be formed in an organ and translocated to another organ
e.g) Nicotine alkaloid of tobacco formed in root then translocated to leaves
2

6 Function Of Alkaloids In Plants:1) Protective against insects & herbivores Duo to their bitterness and toxicity
2) Products of detoxification in metabolic reaction
3) Source of nitrogen in case of nitrogen deficiency
4) Growth regulators in certain metabolic system e.g) Colchicine

5) Source of energy in case of deficiency in CO2 assimilation Alkaloids containing

Sugar moiety

7 Nomencalture Of Alkaloids a-The trivial name should end by Ine

b-These names refer to:
1) Plant genus

Atropine from Atropa Belladonna

3) Common name

Ergotamine from Ergot

2) Plant Species

4) Physiological action
5) Physical characters

6) Name of discoverer

Cocaine from Erythroxylum Coca

Emetine has Emetic action

Hygrine is Hygroscopic
Pelletierine Pelletier

Prefixes
NOR

Suffixes

means N-demethylation

DINE

e.g) Nornicotine = N-demethyl nicotine Cinchonine

Dextro

Quinine

means Isomerism

Optical

Optical

Dextro

APO means Dehydration

ININE

Means different types of isomers

3

Quinidine

means lower pharmacological activity

more active

ISO ,PSEUDO ,NEO ,EPI

Levo

Levo

e.g) Ergotamine

e.g) Apomorphine

Cinchonidine

Egrotaminine
less active

N.B: Levo is more active than Dextro

8 Nitrogen Of Alkaloids :A- No. of Nitrogen atoms
1- Alkaloids usually contains one N but may contain more than one up to 5N
e.g)

Nicotine has 2N

Ergotamine has 5N

B-Type of Amino group:

1- Primary Amino Group

e.g) Nor-Pseudoephedrine

2- Secondary Amino Group

e.g) Ephedrine

3- Tertiary Amino Group

e.g) Nicotine & Atropine

4- Quaternary Amino Group

e.g) Tubocurarine

9 Basicity Of Alkaloids :a) Alkaloids are basic due to presence of lone pair of electrons on N
b) Alkaloids resemble ammonia NH3 in chemical characters which they form
salts with acids without liberation of H2O
c) Factors affecting basicity:
1) Structure of molecule
Unsaturation of Heterocyclic ring decreases the basicity
e.g) Piperidine alk. Is more basic than Pyridine

2) The Presence and position of other substituents

I.

Electron donating group

e.g) Alkyl Group increase basicity

II.

Electron withdrawing group e.g) Carbonyl Group decrease basicity

III.

Some alkaloids are amphoteric due to presence of acidic group such as

Phenolic alkaloids

e.g) Morphine

Alkaloids containing carboxylic group

e.g) Narceine

10 Physical Characters Of Alkaloids :a) Condition:

Most alkaloids are crystalline solids
Some alkaloids are liquids which may be
Volatile

: Nicotine & Coniine

Non Volatile

: Hyoscine & Pilocarpine

b) Color:
Most alkaloids are colorless
Some alkaloids are colored
Yellow

: Colchicine

Orange

: Canadine

Copper Red : Salt of sanguinarine

c) Optical Activity:
Most alkaloids are optically active Due to Chiral Carbon
Optically active isomers show different physiological activity
e.g) Cinchona alkaloids l-Quinine Antimalarial d-Quinine Anti-Arrythmia
Usually l-Isomers is more active than d-Isomers
e.g) l-Ephedrine

is 3-5 times >

l-Ergotamine is 3-4 times >

d-Ephedrine
d-Ergotamine
5

But there is some exceptions :

1) d-Tubocurarine is more active than l- Form
2) d-Quinine & l-Quinine have same activity
3) The Racemic mix dl-Atropine is physiological active
d) Solubility:
Important for isolation & purification
Alkaloids bases are soluble in organic solvents and insoluble in water
Alkaloids salts are soluble in water and insoluble in organic solvents
Both bases and their salts are soluble in alcohol
There are some exceptions
1. Bases soluble in water
Caffeine ,Ephedrine ,Codeine ,Colchicine, Pilocarpine & Quaternary ammonium bases
2. Bases insoluble or sparingly soluble in certain organic solvents
I.
II.

Morphine & Psychotrine

Theobromine & Theophylline :

Insoluble in Ether
Insoluble in Benzene

3. Salts insoluble in water

Quinine Monosulphate
4. Salts soluble in organic solvent
Lobeline HCL & Apoatropine HCL soluble in CHCL3

11 Chemical Characters Of Alkaloids :a) Oxygenated & Non Oxygenated Alkaloids

b) Salt Formation
c) Stability
a) Oxygenated & Non Oxygenated Alkaloids
Most alkaloids contain oxygen Beside C ,H, N
Few alkaloids doesnt contain oxygen
6

e.g) Nicotine & Coniine

b) Salt Formation
1) Basic Alkaloids
Strong base Alkaloid form salt with weak acids
Weak base Alkaloid form salt with strong acids
Very weak base gives unstable salts

e.g) Caffeine ,Nicotine ,Piperine

Dibasic alkaloids contain 2 basic N form 2 series of salts

2) Amphoteric alkaloids form salts with acids & bases
e.g) Alkaloids containing phenolic or COOH group like Curarine & Morphine

3) Acidic alkaloids dont form salts with acids e.g) Ricinine

c) Stability
Alkaloids are less stable in solution than crystals
Alkaloids salts are more stable than free bases ,so they are commercially
found as salts
Factors affecting stability
1) Effect of heat
Alkaloids are decomposed by heat except Caffeine that sublimes
without decomposition
2) Effect of heat & light in presence of Oxygen
Most 3ry amines alkaloids are easily transformed to N-Oxides when
exposed to light in presence of oxygen
N-Oxides are characterized by
I.

Water soluble

II.

Delayed release

III.

Low toxicity

IV.

Low addictive properties

7

3) Effect of acids
Hot dil. Acids and conc. Mineral acid may cause
Dehydration: Produce anhydrous alkaloid APO
Morphine + Acids

H2o

Apomorphine

Atropine + Acids

H2o

Apoatropine

Demethylation: Produce phenolic alkaloids when treated with HI

Codeine

+ HI

CH3

Morphine

Hydrolysis of esters alkaloids to give corresponding acid and alcohol

such as Atropine ,Reserpine & Glyco Alkaloid
4) Effect of Alkalis
a. Weak alkalis like NH3 liberate alkaloids from salts to give free alkaloid bases
N.B: Weak alkalis form salts with alkaloids containing COOH group
e.g) Narceine with NaHCO3 weak alk. Giving Na Narceinate salt
b. Strong alkalis like NaoH ,KOH form salts with phenolic alkaloids e.g)Morphine
c. Hot alkalis Cause
Hydrolysis of esters alkaloids e.g) Atropine ,Cocaine ,Physostigmine
Cleavage of lactone ring if present to produce the corresponding acid

Pilocarpine
Pilocarpic Acid
Alkali

N.B: This Cleavage cause loss of activity

12 Tests for detection & Identification :1) Precipitation Reactions

2) Color Reaction
1) Precipitation Reactions
a) The precipitation reagent added to a neutral or slightly acidic solutions of
alkaloids salts
b) The reagent used usually contain heavy metals such as Hg ,Pt & Bi and form
double salts with most alkaloids
c) These reactions are used for extraction or purification or detection
Reagent + alkaloid

PPT Wash wz water + Supernatant

d) Precautions on PPT Rx
Certain alkaloids Caffeine ,Ephedrine doesnt form PPT
False positive response may be obtained with proteins ,Tannins
,Coumarins and certain Flavonoids
2) Color Reactions
a) Strong free base + coloring reagent to produce characteristic color
b) Generally reagent contain C.H2So4 + Oxidizing agent
c) Examples of specific color Rx
Van-UrkS test for ergot alkaloids Give blue Color
Vitalis Test for solanaceous alkaloids Violet

 Composition of common reagents used for detection

Name of Reagent
Alkaloids Precipitants
1) Mayers

Remarks

Composition
Potassium-mercuric iodide

Color of precipitate
Creamy white (positive with most

alkaloids except caffeine & dil.Ephedrine)

Reddish brown

2) Wagners

Iodine in potassium iodide

3) Hagers

Saturated solutions of picric acid

Yellow

5) Marms

Potassium Cadmium iodide

Yellow Precipitate

4) Dragendorffs
Color Reagent
1) Froehds

2) Mandalins
3) Marquis

4) Erdmanns
5) Shaers

6) Dragendorffs

Potassium bismuth iodide

Orange reddish brown

Ammonium molybdate/Conc. H2So4

The color formed are

Ammonium vanadate/Conc. H2So4

Formaldehyde/Conc. H2So4

Conc. Nitric acid /Conc. H2So4

Hydrogen peroxide /Conc. H2So4

characteristic. The tests are

sensitive to micro amounts and
can be used for colorimetric assay

Potassium bismuth iodide

13 Extraction ,Purification &Separation : Alkaloids occur in plants with inert constituents such as tannins ,Fats

,Proteins Which hinder isolation

Procedure of extraction ,Purification &Separation

1) Preparations of the plant sample

2) Extraction & Purification
3) Liberation ,Extraction of alkaloids bases
4) Purification of crude alk.Mixture
5) Separation of individual alkaloids
1) Preparations of the plant sample
The plant material is carefully dried , powdered and defatted with petroleum
ether in case of seeds
10

2) Extraction & Purification 2 Methods

Method 1
a) The powder is treated with lime water Ca(OH)2 to liberate the free bases
b) Alkaline extract then shaken with CHCL3 ,the organic layer is separated &
concentrated
c) The concentrated organic layer then shaken with aqueous acid to form
alkaloidal salt in aq.Layer which can be seprated
Method 2
a) The powder material is extracted with water or aqueous alcohol
containing dilute acid ,so alkaloids are extracted as their salts together
with soluble impurities
b) the acidic extract is shaken with CHCL3 to remove impurities
3) Liberation ,Extraction of alkaloids bases
A. Factors limiting selection of alkaloids in method 1
I.

Nature of plant material

If plant material is fatty nature ,the strong alkali shouldnt be used to

prevent saponification that form emulsion
II.

Nature of alkaloids salts

Salts of strong bases with mineral acids need use of stronger alkali
III.

The chemical nature of alkaloids bases

Strong alkali shouldnt be used in case of

Esters alkaloids Atropine ,Cocaine to prevent Hydrolysis
Phenolic alkaloids morphine ,Cephaline to prevent formation of
Phenates

11

 Alkaloids contain lactone ring Pilocarpine to prevent cleavage of

lactone ring & Loss of activity
N.B: Amonia is the alkali of choice ??
a-Basic enough to liberate most of alkaloids
b-Volatile ,easily removed after extraction

B. Selection of solvents for extraction

1) Aqueous acids: cheep but non-selective in extraction of alkaloids as their
salts Impurities may be extracted
2) Organic water immiscible solvents extract most alkaloids except
quaternary ammonium bases as they are insoluble in organic solvents
3) Organic water miscible solvents: methyl or ethyl alcohol used to extract
both alkaloids and their salts
4) Purification of crude alkaloid mix
a) Dissolution in organic solvent followed by acid-base shake up
b) Complex formation by suitable PPT followed by decomposition to recover
alkaloids
I.

Tannic complex decomposed by pb(OH)2

II.

Mayers complex decomposed by H2S

III.

Picric complex decomposed by NH3

IV.

Dragendroffs complex decomposed by Na2Co3

12

5) Separation of individual alkaloids

a) Fractional precipitation or crystallization, derivatization to salts such as
Oxalate ,Tartarates & Picrates depends on formation of salts
b) Gradient PH extraction for separation of alkaloids of different basicity
weakly ,moderately & strongly basic
c) Chromatographic techniques :The most suitable in case of complex mixture
e.g) TLC ,HPLC
Example:
Atropine ,Hyoscine ,Hyoscyamine ???
1) Add NaHCO3 weak alkali to liberate the weak basic alkaloid hyoscine
then extract by ether to get hyoscine PH
2) Add NH3 + organic solvents to get atropine & Hyoscyamine bases then add
oxalic acid ,atropine form oxalate but hyoscyamine doesnt form oxalate
fractional PPT

14 Isolation of volatile & sublimable alkaloids :a. Isolation of volatile alkaloid nicotine by steam distillation
1. The plant material is immersed with water
2. Add NaOH or KOH to liberate free bases avoid NH3
3. Steam distillation
b. Isolation of sublimable alkaloid Caffeine could be directly isolated from the
powdered plant material by sublimation.

13

15 Quantitative analysis :A. Purpose :

1. Determination of :
Genuinesses of raw vegetable material
Site of biosynthesis in the plant
Bioavailability in different organs & tissues
2. Evaluation of :
Plant material for marketing
Stability & activity of the preparation
3. Prevention of overdose toxicity
4. Selection of the best stage of collection
B. Types of assay :
1. The ultimate assay : Used for determination of individual alkaloid
2. The proximate assay : Used for determination of total alkaloid
a. Volumetric method :
Based on the quantitative Rx of alkaloids with acid to form stable salts
This method is simple & accurate
Impurities are removed by pet. Ether before titration
Titration may be :
(I)

Aqueous titration : for strong basic alk.

1. Direct titration : alc. Sol. Of alk. Residue against standard acid
2. Back titration : add known amount of standard acid to dissolve residue
of alk. Then back titrate the residual acid against std. alkali

14

(II)

Non aqueous titration : for weak basic alk.

The purified residue is dissolved in glacial acetic a or chloroform
then titrated with st. percholic a

b. Gravemetric method :
For determination of :
1. Very weak bases Caffeine , Colchicine
2. Mixture of alkaloids that are obtained from the same plant but differ
greatly in m.wt like Cinchona alkaloids
This method can be performed by either :
1. Weighing the purified residue
2. Precipitation of the total alkaloids by complexation and determination
of the weight of the ppt obtained followed by calculation
Major drawbacks of this method :
1. Insensitive to micro amounts of alkaloids
2. Thermolabile constituents can not be determinated
3. Lipophilic impurities are calculated as alkaloids.
c. Other methods :
1. Colorimetric method e.g. Solanaceous alkaloids using Vitali test
2. Spectrophotometric
3. Chromatographic techniques HPLC , TLC
4. Polarimetric optical activity .

DR.M.F
15

A ALOIIDS WITH
ALKA
W
E CYCL
EXOC
LIC NIITROG
GEN
PRO
OTO ALKA
A ALOID
DS
1 Known
1.
n as bioloogical amiines
2 No hetterocyclicc nitrogen
2.
n
3 Many are simplle derivattives of ph
3.
henylethyylamine and
a are derived
d
frrom the
commoon aminoo acids likke phenyllalanine , tyrosine
4 They are
4.
a sympaathomimeetic drugss , known
n as presssor drugs as theyy raise thee
blood pressure
p

EPH
HEDRA
A ALKA
ALOID
DS
1 Ephedrra or Maa Huang in Chinaa , refers to
1.
t the aerrial parts of severaal
Ephedrra speciess Fam. Ep
phedraceaae
2 The drrug contains 0.5-2
2.
2% of alkaaloid , am
mong thesse (-)epheedrine , l-ephedrrine and their
t
sterreo isomer (+)pseu
udoephedrine (d- -ephedrrine)

Eph
hedrine :
1 Occuraance :
1.
Ephedrrine : Eph
hedra siniica , Epheedra equiistina
d-pseu
udoephed
drine : Eph
hedra vulgaris
Part ussed : Herb
b

2. Structure :
Ephedrine is -OH--methyl-aminopropyl-benzene
Ephedrine is structurally related to animal hormone Adrenaline or
Epinephrine
3. Properties :
a. Colorless , crystals
b. Strong base , soluble in water EXCEPTION , soluble in organic solvent
c. Free base is volatile with steam advantage
d. Doesnt give ppt with Mayers reagent except in conc. Form
e. Chloroform is not recommended for the extraction of ephedrine ??
Because ephedrine in aged chloroform solution or on evaporation is
transformed to its hydrochloride with release of toxic aldehyde phosgene
4. Preparation :
A. Isolation from plant material :
a. Steam distillation
b. Extraction with benzene instead of CHCl3
c. Shaking with acids dil HCl which extract ephedrine &
pseudoephedrine as HCl salts then the mixture is separated
B. Fermentation :
For large scale production
Produce dl-ephedrine racemic mix
a. Benzaldehyde + molasses fermentation
b. Keto-alcohol phenyl acetyl carbinol + methyl amine & allow
reduction +H2 to give dl-ephedrine
2

C. Cheemical syn
nthesis :
a. Condensa
C
ation betw
ween benzzaldehyde + nitro ethane in
n presencce of
K2CO3 to give
g nitroo alcohol
b. Reduction
R
n then meethylation
n to give dl-ephed
d
rine

K2CO3
Noreephedrine

Ephedrine

(***) Separaation of ephedrin

e
ne from the less active pseudoep
p
phedrinee :
a Ephedrrine is moore solub
a.
ble in watter than pseudoeph
p
hedrine
b Ephedrrine oxalaate is lesss soluble in
b.
i water than pseu
udoephed
drine
c Ephedrrine HCl is less solluble in chloroform
c.
c
m& alcoh
hol than pseudoep
p
phedrine
All dep
pend on Fractional
F
l precipittation
5 Tests foor identiffication : Chens test
5.
Ephedrrine in water
w
+ 2 dps
d CuSO
O4 + NaOH
H give vioolet col. + ether orr benzenee
blue in
i aq. Layyer , purp
ple in orgganic layeer
6 Uses :
6.
a. Sym
mpathomiimetic am
mine with effect sim
milar to noradrena
n
aline
b. Effeective orally c.f. nooradrenaaline and
d has longger duration than
noraadrenalin
ne
c. Antii-asthmaatic & used
d in couggh due to its broncchodilatorr activityy
d. Poteent nasal decongesstant due to vasocoonstrictor action

KHAT ALKALOID
A
DS
1. Plant
P

2. Alkaloid
A
3. Occurance
O

PEYOTE
E ALKALOID
DS

COLC
CHICUM ALK
K.

*Common
n name : Khaat

*Common name : peyoote *Part useed :

*Part used :

*Latin naame :

*Latin naame :

Colchicu
um seeds &

um fruits
Capsicu

Abyssiniaan tea

Mescal buttons
b

corms are
a obtained

Fam. Sollanaceae

*Part used : fresh leavees

*Part useed : dried topss of

from Coolchicum

*Cultivated in Ethiopiaa

Cactus Loophophora

autumn
nale

n
& Yemen

Williamssi

Fam. Liliaceae

*Leaves are
a chewed

Fam. Cacctaceae

habituallly to alleviate

*Plant caause mydriasiss ,

the sensaation of hungeer

hallucinaation &

& fatiguee

euphoriaa

Cathinee & Cathinonee

M
Mescaline

Colchiciine&Colchiceeine

C
Capsaicin

Cathine or
o

N.B : Coolchicum alk.

The van
nillyl amide off

norpseud
doephedrine &

have sevven membereed

isodecen
noic acid

pseudo aromatic
a

not solaanaceous alk..

Ephedra vulgaris &

unsaturated ring

no trop
pane nucleus

Khat

tropoloone nucleus

cathinon
ne occur in

4. Structure
S

If OCH3 is
i OH : Colchiceeine
1

CAPS
SICUM ALK
K.

5. Properties

a. Crystals

a. Cathine is dextro

b. Moderately soluble

rotatory and gives

+ve with Chens test

in water
c. Sol. In alc. , CHCl3 ,

b. Cathinone is levo

benzene

rotatory and gives

d. Insol. In ether ,

+ve test for ketone

pet.ether

a. N-acetyl derivative
amide

c. Sol. In ethanol &

& tyrosine amino a

organic solvents

c. Yellow needles
d. Sol. In water , alc. &
chloroform

a. Hallucinogen or
psychomimetic

principle CNS
stimulant of the

b. Psilocybin from

fresh plant

mushrooms &

b. Has similar effect to

amphetamine

oxidation KMnO4

f. Has not basic

colchicine gives

characters due to

colchiceine +

presence of

menthol

nitrogen in amide

a. Ttt of gout relief

gp
a. Counter irritant

pain & inflammation b. Rheumatoid

around joints
b. Antitumor in dogs

diethyl amide are

cytotoxic in required

hallucinogens

dose for human

use of mescaline

e. Pungency is

f. On ttt with milds

and mice but

result from repeated

taste to water
destroyed by

LSDlysergic acid

c. Addiction doesnt

d. Imparts a pungent

e. Insol. In pet.ether

g. Weak basic alkaloid

a. Cathinone is the

b. Insol. In cold water

b. From phenylalanine

acids or alkali :

6. Uses

a. Phenolic amide alk.

c. Plant hormone, it
increase polyploidy

arthritis &
osteoarthritis
c. Neuralgia , diabetic
neuropathy

7. Identification

1.+ Marquis reagent

1.Colchicine + mineral

gives orange colour

acid

2.+ammonium

2. Colchicine +

molybdate gives green

conc.HNO3

converts to yellow

green

Determination :

yellow

yellow col.
dirty

brown

By colorimetric methods 3. FeCl3 test to

by formation color with

differniate between

P-nitrophenyl

colchicine &

diazonium chloride or

colchiceine

picric acid

*colchicine

garnet

red col.
*colchiceine

olive

green col.

8. Isolation

Isolation og Colchicine :

1.Powdered capsicum

1.Colchicum + 95% alcohol then concentrate

is extracted with light

2. add H2O

petroleum

ppt fats & resin

3. F is extracted wz CHCl3

syrupy consistency

4. Add alcohol until white ppt dissolved

2. extract + alkali with

CO2 gives capsaicin

5. Solution is kept at 0C , where chloroform additive cpd will crystallize out crystals
6. The additive cpd is suspended in water and decomposed by passing steam
7. On evaporation , crude colchicines is obtained and is recrystallized from
ethyl acetate
3

Synthesis of Mescaline : either by

1. 3,4,5-Trimethoxy-benzaldehyde + Nitromethane
aluminium hydride LiAlH4
** ArCHO+CH3NO2

Nitrosostyrene which reduced by Lithium

Mescaline

ArCH=CHNO2

LiAlH4
Conc.HCL

2. 3,4,5-Trimethoxy-benzyl alcohol

Mescaline
KCN

Chloride derivative

HCHO

HCOOH

which reduced by Lithium aluminium hydride LiAlH4

** ArCH2OH

Conc.HCL

ArCH2Cl

HCHO

HCOOH

KCN

ArCH2CN

Mescaline
LiAlH4

Mescaline

Phenylacetonitrile

PYRIDINE ALKALOIDS
Alkaloids of Pyridine group:
Subclassified acc. To basic nuclei to
1) Pyridine nucleus : Trigonelline
2) Pyridine nucleus with another nitrogen ring : Tobacco
3) Tetrahydro Pyridine nucleus : Areca alk.
4) Piperidine nucleus : Lobelia & Pomegranate alk.
5) Pyridone nucleus : Ricinine Alk.
1) Trigonelline ( Coffearine , Gynesine )
Occurrence : In some seeds as Foenugreek, Coffea bean, Strophanthus
Excecreted from urine after intake of nicotinic acid
Properties
Monohydrate salts
Very Sol. In water , Sol. In alc. , practically Insol. In ether & chloroform
Derived from Nicotinic acid ( Biosynthesized from L-tryptophan aa\ )
Alk. + HCL

260C

Alk. + Barium OH

Methyl CL- + Nicotinic a\

Methyl amine

Isolation
Seeds are Defatted by light Pet. Ether Then Extracted with water
Aqueous Extract + H2SO4 Acidification + Ether + Mayers reagent
PPT Filter

Suspended in methanol

H2S Gas

 Uses
Trigonelline is used as a Hypoglycemic drug in diabetic patients , as it slows down
metabdism of nicotinic acid
2) Tobacco Alkaloids:
Nornicotine

Nicoteine

Nicotelline

Nicotine , Nornicotine , anabasine : volatile , but nicoteine & nicotelline non volatile
Occurrence :
Dried leaves of nicotiana tobacum F. Solanaceae
Tobacco alkaloids present as salts : Citric & Maleic
N.B : Nicotine represent 2/3 of total alkaloids
Nicotine
Very Hygroscopic
Volatile with steam
Miscible with water
Has 2 basic N atoms
So it can unite with 2 molecules of monobasic acids
Weaker base nitrogen in present in pyridine ring
So it forms salts with acids ( HCL, Tartarate) than nitrogen in Piperidine ring
Nicotine

UV

nicotine oxide + nicotinic acid + methylamine

Optically active : Having 2 enantiomers forms

The naturally occurring form of nicotine is Levorotatory with specific rotation
N.B : Dextro form (+) nicotine is physiologically less active than (-) nicotine

 Color test
P-dimthylaminobenzaldhyde

Red rose

Violet

Aq. Solution of nicotine +

Vanillin HCL
Nicotine + Cyanogen bromide

Red color

Orange Color
Powdered leaves
Acidification with H2O/HCL

Concentration

Extract
Alkalization with NaOH + Steam Distillation

Distilled Fraction

Uninstalled Fraction

Volatile alkaloids

Extraction with benzene

(Nicotine , Nornicotine & Anabasine )

Evaporation

Extraction with ethers

Residue

Non volatile alkaloids

Ether Extract

(Nicoteine & Nicotelline)

Evaporation &

Solubilization in ether

treatment with HCL & NaNO2

On Cold
Oily Layer

Nitrose derivatives
Of Anabasine & Nornicotine
Heating wz HCL

Concentration

Aqueous Layer

Mother Liquor

Nicotine HCL

Evaporation

Alkalization wz Naoh

Alkalization wz Naoh

Extraction of ethers

Extraction wz ether

Evaporation

Evaporation

Residue

Anabasin & nornicotine

Nicotine

(Liquid , 3ary amine)

(Liquid , 2ary amine)

Fractional distillation

Under reduced pressure

Anabasin

Nornicotine
3

Nicoteine
(Liquid)

Crystals

Nicotelline
(Solid)

Nicotine : 3ry amine

Nornicotine : 2ry amine

Anabasine : 2ry amine

Estimation of Nicotine and Nornicotine :

1. Trimetric method : dried plant material ttt with NaOH solution , steam distilled into std
acid solution known xss
2. Spectrophotometric method : acid solution contain both alkaloids measured for
absorbance at 260 nm
Uses
1. Nicotine has little use in medicine because of high toxixity
2. in small doses : respiratory stimulant
3. in large dose : respiratory depressant
4. Etiology of some cardiovascular disease , chronic obstructive lung disease
5. Insecticide Imidacloprid
4) Piperidine Alkaloids:
Piperidine nucleus can be obtained by hydrogenation of Pyridine using nickel as
catalyst
Biosynthesized from l-lysine amino acid
Pepper Alkaloids
Occurrence : Fruits of pepper species F:Piperaceae
Main alkaloids are piperine & chavicine
Structure : weak base because of amide gp electron withdrawing gp as capsaicin

 Properties :
ms
1. Colorrless , odorrless prism
2. Weakk base
3. Form
ms unstablee salt
4. Piperrine with alc.
a KOH giives piperiidine + pip
peric acid

Color teest : Piperin

ne + H2SO4 gives red
d color
Uses :
diment
1. Cond

2 Tonic and rubefaciient

2.

3. Stimu
ulant , carm
minative and
a tonic
Chronicc toxicity : Loss of tasste buds in
n tongue , C.I in liverr dysfunctiion
Loobelia Alkaaloids
Occurreence : Lobeelia herb or
o Indian toobacco
Structurre :
Partial
reduction
Lob
belanine

Lob
beline

Com
mplete
redu
uction

 Lobeline : Keto alcohol , forms mono-oxime & monoester

Lobeline HCL salt is soluble in CHCl3
Lobelanine : diketonic compound , forms a dioxime meso cpd , inactive
Lobelanidine : Possess 2 OH so forms diester , not form any oxime
Isolation : IMP
Pd. + water + acetic acid , take the extract + Na2CO3 + ether then evaporate and take the
residue + HCL + CHCl3 only lobeline HCL is extracted
Color tests : Lobeline +
1. Marquis : red violet color
2. Erdmanns : faint green color
3. Froehds : rose red color
Pharmacology :
1. Produce similar pharmacological effect as nicotine
2. Lobeline sulfate incorporated in tablets or lozenges , intended to aid breaking
tobacco habit
Uses :
1. Respiratory stimulant in small dose
2. Expectorant in Bronchial asthma used in hypertensive people wz asthma

Pomegranate Alkaloids
Occurrence :
Fruit , roots and stem of pomegranate , Punica granatum F. Puniaceae
Alk. Are : Pelletierine , Isopelletierine , MetN-hyl Pelletierine , Pseudo Pelletierine
Structure :

Pelletierine

IsoPelletierine

NmethylPelletierine

Pseudopelletierine

Properties
o Pelletierine : Liq. ,Strongly basic , Sol. In H2O , Sulphate Salt
ry

Insol. In H2O

o Isopelletierine : Liq. ,Strongly basic , 2 amine , Ketonic properties

o N-Methylpelletierine : Liq. ,Weak base
o Pseudopelletierine : Solid ,Weak basic , Very Sol. In H2O , Insol. In ether

Powdered Bark
(Alkaloidal Tannates)
Maceration With Ca(OH)2
(Liberation of bases & Precipitation of Tannins)
Extraction with CHCL3

Chloroform Extract
(Alkaloidal Bases)
Extraction with HCL

Acidic aqueous layer

(Alkaloidal HCL)
Maceration With NaCO3
(Liberation wz weak bases)
Extraction with CHCL3

Chloroform Layer

Alkaline Aqueous Layer

(Weak alkaloids bases)

(Hydrochlorides of strong bases)

Methylpelletierine & Pseudopelletierine

Pelletierine HCL & Isopelietierine HCL

Evaporation

Alkalization wz NaOH&

Extraction with ether

Extraction with CHCL3

Concentration
Crystals
Pseudopelletierine

Chloroform extract
(Strong alkaloidal bases)

Mother Liquor

Pelletierine & Isopelletierine

Acidification wz dil.H2SO4

Evaporation

Methylpelletierine

Concentration

Drying in Dessicator

Pelletierine Sulphate
(Crystals)

Isopelletierrine Sulphate
(Oily)

Uses

Pelletierrine Tannate : Official in E.P , Mainly used as anthelmintic drug against tape
worms and Ascaris , used was laxative as castor oil to expel the worm
Also used as Taenifuge & Vermifuge
N.B : Pelletierine is toxic if absorbed so used as pelletierine tannate as enema

5) Pyridone Alkaloids:
Ricinine
Occurance

Seeds of castor , Ricinus communis F. Euphorbiaceae

Properties

Colorless Prisms , acidic so not form salts with acids

Sparingly Sol. In cold water , Alcohol , CHCL3 & Ether

Isolation not imp

Seeds +

H2O

Evaporate under vacuum , R

Extracted wz boiling Ethanol

Gives Conc. Results in PPT of crude ricinine

Tests For Identification:

Color Test
i.

Decolorize solution of KMnO4

ii.

+ Conc. HNO3

iii.

+ Wagners & HgCl2

iv.

Mayers

Yellow residue

Red

PPT

No PPT as caffeine and dil ephedrine

Toxicity not imp

Ingestion cause: Nausea , Vomiting , Hemorrhage , Hepatic & Renal damage ,

Convulsions , Coma , Respiratory depression , Death

ALKAL
A
LOIDS OF TR
ROPAN
NE GP
General
G
ch
haracters :
1 Formed
1)
d by conden
nsation of Pyrrolidin
ne & Piperiidine with one N atoom in comm
mon
2 Are derived from L-Ornithiine
2)
3 Tropanee nucleus is
3)
i a seven C , bicyclicc ring.
4 Contain
4)
n 2 asymm
metric carboons at C1 and
a C5 ,bu
ut it is optically inacttive .
5 Tropanee alkaloidss are esterss alkaloids , formed by
5)
b esterificcation of an
n alcoholicc base.
6 Being esters , theyy are unstaable toward
6)
ds acids , alkalis
a
and are therm
molabile.
7 Tropanee is a paren
7)
nt base of several alkkaloids obttained from
m a numbeer of families
Solan
naceae : Attropine , Hyoscyamin
H
ne , Hyoscine
Eryth
hroxylaceaae : Cocain
ne , Cinnam
myl Cocain
ne
Convvolvulaceaae : Convollvine
Diosscoreaceaee : Dioscoriine
1) Solanaceou
S
us alkaloid
ds :
A Occurreence :
A.
Bellaadonna leaaves : Hyosscyamine , Atropine , Scopolam
mine , Apoaatropine
Bellaadonna rooots : Hyosccyamine , Scopolamin
S
ne
Hyosscyamus niger
n
leaf : Hyoscyam
mine , Atrop
pine, Scopoolamine, belladonnin
b
ne
Hyosscyamus muticus
m
leaaf : Hyoscyyamine , Attropine , Sccopolamine , Apoatroopine
Datu
ura stramoonium leaf : Hyoscyam
mine , Atroopine ,Scop
polamine
B Alcohollic bases off alkaloids:
B.

Tropine

Pse
eudotropine

Ecgonine

Scopinee

1. Tropine : base of atropine and hyoscyamine

2. Pseudotropine :base of tegloidine
3. Nor-tropine : base of nor-hyoscyamine
4. Teloidine : base of meteloidine
5. Scopine : base of hyoscine
6. Ecgonine : base of cocaine
C. Acids which make esterification to tropane alkaloids :

lTropicacid

Atropicacid

Isovalericacid

Tiglicacid

1. Tropic acid : Optically active l-form : hyoscyamine , hyoscine

Optically inactive dl : atropine
2. Atropic acid : apoatropine
3. Isotropic acid : belladonnine
4. Tiglic acid : meteloidine
5. Isovaleric acid : valeroidine
Atropine

Hyoscyamine

Hyocine

Atropine

Hyoscyamine

Hyoscine

1.Name

dl-hyoscyamine

Scopolamine

2.Occurrence

Doesnt occur naturally Family Solanaceae

Family Solanaceae

, by racemization of

Atropa , Datura ,

Hyoscyamus muticus ,

hyoscyamine

Hyoscyamus

Datura , Scopolia

3.Properties

1. Hydrolysis by dil acid 1. Hydrolysis by dil

1. Hydrolysis by dil acid

or alkali gives dl-tropic

acid or alkali gives dl- or alkali gives tropic acid

acid + tropine base

tropic acid + tropine

+ Scopoline

2. Soluble in ethanol

base

2. Hydrolysis by enzymes

and crystallizes from it

2. Easily converted to

gives tropic acid +

on addition of water

atropine by keeping

Scopine

3. Soluble in CHCl3 and its alcoholic solution

3. Optically active , l-

crystallizes from it by

in presence of dil acid form

pet.ether

or alkali or by

4. Racemize when treated

4. less soluble in ether ,

keeping it at Temp.

by dil alkali

benzene , water

above its m.p.

5. Syrupy liquid

5. Atropine sulphate is

6. Soluble in water,

incompatible with

Pet.ether , Benzene

alkalis , Tannins , salts

of Hg , gold ,
borax,vegetable
decoctions &infusions
4.Uses

1. Anti-cholinergic Parasympatholytic

1. Hyoscine HBr :

2. Mydriatic dilation of eye pupil

Sedative , mydriatic , CNS

3. Antispasmodic relax bronchial and intestinal depressant

smooth muscles
4. CNS stimulant
5. Antidote for organophosphorus insecticide
6. Preanaethetic medication to stop body
secretion in a combination consists of
a. Tubocurarine : SMR
b. Atropine : Dryness of body secretions
c. Morphine : Narcotic analgesic
3

D Isolation
D.
n of Solanaaceous alkkaloids : im
mp
Sepaaration of Hyoscine
H
f
from
Atrop
pine & Hyooscyamine depend on
n the differrence in
theirr basicity , Hyoscine is a weakeer base
Sepaaration of Atropine
A
frrom Hyosccyamine is based on the
t differeence in theeir
solub
bility of th
heir oxalatees in a mix
xture of acetone & eth
her
Isolaation :
1. Plant ex
xtracted wzz 95% ethaanol , evap
porate (not methanol which is toxic
t
and
also ethaanol has higher peneetration poower to plaant cells)
2 Residue + HCL theen extract with
2.
w CHCll3
3 Acidic extract + Naa2CO3 + etther to gett Hyoscinee in ether laayer, it is weak
3.
w
base
4 Aq. Extract + NH4OH
4.
O + CHCl3 then evaaporate
5 Residue + oxalic accid + acetoone + etherr
5.
6 Atropinee oxalate iss soluble but
6.
b hyoscyaamine oxaalate is morre soluble , so by
fractional crystalliization atroopine oxallate crystalllizes first
E Quantittative deterrmination of Atropine , Hyosccyamine an
E.
nd Hyoscin
ne :
1. Totaal alkaloidss , by norm
mal volumeetric methood (A)
2. R + dil
d HCL , pu
urified exttract + Na bicarbona
b
ate , Hyosciine extractted with etther
3. Resid
due is dissoolved in allcohol then
n titrated with
w std accid (B)
4. Resid
due is dissoolved in allcohol , meeasure the optical rottation of Hyoscyamin
H
ne (C)
Atroopine is op
ptically inaactive
5. % off Atropine = A- (B+C))
F Synthessis of atrop
F.
pine :
Conden
nsation betw
ween Succcinaldehyd
de + methyyl amine + acetone
a
diicarboxylicc acid

G. Tests for identification of tropane alkaloids :

1. Vitali-Morins test : imp
Fuming nitric acid , evaporate

yellow residue + alc.KOH

bright purple or

violet color
2. Gerrards reaction:
HgCl2 in 50% ethanol , if red Hyoscyamine , if white ppt Hyoscine
2) Coca Alkaloids:
A. Occurrence : obtained from Bolivian Coca Erythroxylum Coca or Peruvian Coca
E.troxellina family : Erythroxylaceae
B. According to chemical structure , Coca alkaloids are classified into 3 types not imp
1. Ecgonine derivatives : Cocaine , Cinnamyl cocaine
2. Pseudotropine derivatives : tropococaine
3. Pyrrolidine derivatives : hygrine , cusohygrine
1. Ecgonine derivatives :
* Contain acidic & alcoholic gps
* acidic gp : in most cases esterified wz methyl alcohol
* alcoholic gp : esterified wz different acids , giving different alkaloids
* major examples : Cocaine , Cinnamyl Cocaine

C
Cocaine
A Properties :
A.
d
1. Diestter alkaloid
2. Levorrotatory
3. Solub
ble in wateer
4. 3ry amine
a
basic
5. Liablee to decom
mposition
6. On hydrolysis
h
: Ecgonine + methyl alcohol
a
+ benzoic
b
aciid
7. It cau
use numbn
ness of lips & tongue
B Isolation
B.
n : not im
mp
Leaves + lime or Na
N 2CO3

extract with pet.ether + dil.HCl

d
givving HCl saalt , then

acidic solution is concentrat

c
ted , crystaals of Cocaaine HCl is obtained
C Semisyn
C.
nthesis : froom Java Cooca leaves :
1. When
n Cocaine occurs in low conc
2. Boiled with dil HCl hydrrolysis of essters

ecgonin
ne base + CH
C 3OH +

esterifyyying acid , then filterr

3. Filterrate is conccentrated and
a ecgoniine HCl cryystallized out
o
4. Ecgon
nine HCl + Na2CO3 , liberate frree ecgonin
ne base
5. Benzooylation wz
w benzoic anhydridee

beenzoyl ecggonine is ob
btained, byy

methylaation CH3I + NaOCH

H3
D Synthessis of Cocaiine :
D.

Cocaine
C
6

E. Color test : with PDAB in 100 C for 3 mins gives red color
F. Pharmacology :
Sniffed into nostrils , where it is rapidly absorbed
May be injected or inhaled
Regular use induce depression , dependence , nasal membrane damage
Vaporized Cocaine is absorbed extremely and carried to the brain
No useful antagonist drug available in ttt of addiction
G. Uses :
1. Local anesthetic topically as Cocaine HCl
2. Was used in dentistry , but now replaced by safer ones
3. CNS stimulant followed by hypnotic effect
H. Toxicity : minimal lethal dose is 1.2 g
Cinnamyl Cocaine
A. Occurrence : naturally in java coca leaves , in % higher than Cocaine

B. Properties :
1. solid , insoluble in water but soluble in organic solvent
2. Semisynthetic method is similar to that used for Cocaine but heat ecgonine at 100 C
wz cinnamic acid instead of benzoic acid
C. Test for identification : imp
Cinnamyl Cocaine decolorize KMnO4 solution in acidic media , with liberation of
benzaldehyde odour , this test is used in differentiation between Cinnamyl Cocaine and
Cocaine

ALKALOIDS OF QUINOLINE GROUP

Derived from Tryptophan amino acid
Cinchona alkaloids
Occurrence:
Cinchona bark it obtained from dried stems& roots of diff. species of cinchona F. Rubiaceae
Quinine & Quinidine

Quinine

not less than 50% of total alkaloid

Quinidine

Cinchonine

N.B.

Cinchonidine

Cinchona alk. Are di-acidic bases ( Due to presence of 2N )

They can form both (Neutral & Acidic) Salts
They occur in the plant combined with specific organic acids: Quinic , Cinchotannic ,
Quinovic acid
Quinine properties
Quinine is diacidic base , it forms 3 types of sulfates:
Monosulfate
Bisulfate
Tetrasulfate
Quinine & Cinchonidine
Quinidine & Cinchonine

Neutral / H2O insol.

Acidic / H2O insol.
More H2O insol.
Levorotatory
Dextrorotatory

Tartarates of cinchonine & quinidine are H2O Sol.

Tartarates of quinine & cinchonidine are H2O Insol.

1
`1

Powdered Bark
(Alkaloidal Tannates)
Alkalinization with Cao + NaOH + H2O
(Liberation of free bases & Precipitation of Tannins)
Reflux with benzene & filtration while hot

Benzene Filtrate
(Alkaloidal Bases)
Acidification with dil H2SO4

Acidic aqueous layer

(Alkaloidal bisulphates)
Heating

Adjusting PH to 6.5 with Na2CO3

Aqueous Solutions

Precipitate

(Monosulphates of Quinidine

(Quinine monosulphate)

Cinchonine & Cinchonidine )

Addition of boiling water

Alkalization with NaOH

Aqueous Layer

Extraction with Ether

Cinchonine (Insol. In ether)

Na2Co3
Ether Layer

Quindine & Cinchonidine

Evaporation

Acidification with dil.HCL

Concentration & Crystallization

Addition of Rochelles salt (25%)

Extraction with Alcohol

Neutralization

Cinchonine

Filtration after 24h

Precipitate

Filtrate

Cinchonidine Tartrate
Acidification with dil HCL

Cinchonidine HCL
Cinchonidine
Rochelles Salt

Quinidine Tartrate
Addition of KI

Quinidine HCL

Alkalization with NH4OH

Alkalization with NH4OH

Quinidine

Tartarate

2
`2

Quinine

 Tests
Fluorescence test
Solutions of alk. + oxygenated acids (H2SO4 , HNO3 or Phosphoric acid)

Blue Fluorescence

Thalleioquin test not imp

Aq. soln. alk. Salt+Br2/H2O (Few drops till appearance of yellow col.)+NH4OH

Emerald green

Herpathite test
Alk. Soln. in glacial acetic acid + alcohol 90% + few drops of conc. H2SO4 +1% I2 in alcohol
Crystals of Iodosulphate of alkaloid (+ve Quinine & Cinchonine )
Uses
Used as anti-malarial (2g of quinine sulphate or other salt )
Minimal lethal dose of quinine is 8g
Quinidine: used as a cardiac depressant (Anti-Arrhythmic)
Cinchonine & Cinchonidine are used as Anti-Inflammatory

3
`3

ALKALOIDS OF ISOQUINOLINE GROUP

Derived from Tyrosine amino acid
Ipecacuahna alkaloids
Occurrence:
Dried roots & Rhizomes of Cephaelia Ipecacuaha , Or Cephaelis Acuminata

Emetine

Emetine

Cephaline

Non phenolic . Levorotatory , white amorphous powder

Psychotrime

Sol. In ethanol , ether , and CHCL3 , Sparingly sol. In H2O

Contains 2 basic nitrogen atoms
Cephaeline
Phenolic . Levorotatory , colorless , needle shaped crystals
Insol. In water , Sol. In ether
Gives emetine on methylation with (CH3)2SO4
Psychotrine
Phenolic ,gives caephaline on reduction , yellow prisms
Gives emetine on reduction followed by methylation
Insol. In H2O , nearly soluble in alcohol

Tests for identification

ALk. Solution in HCL + Ca Hypochlorite

Orange Col

Emetine / Cephaline
Froehds reagent +

Psychotrine

Psychotrine + Conc. H2SO4 + HNO3

Dirty green

Pale green
Cherry red Color

Cephaeline & Psychotrine (Phenolic alk.) + P-nitrodiazobenzene dye in NaoH

4
`4

Purple CoL

Isolation Of Ipeca Alkaloid:

Powdered Roots and Rhizome
Extraction with alcohol
Concentration

Purification by lead acetate method & Filtration

Filtrate

Residue

Alkaloidal bases and salts

Coloring matter &

Evaporation to dryness

Non-Alkaloidal Substance

Extraction with dil. HCL

Filtration

Filtrate
Alkaloidal Hydrochlorides

Alkalization with NaOH &

Ether Layer

Extraction with ether

Non phenolic alkaloids

Aqueous alkaline solution

Phenolic alkaloids (as Phenates)

(Emetine)

(Cephaelline & Psychotrine )

Evaporation

Acidification with dil.HCL

Emetine

(Alkaloidal salts)
Alkalization with NH4OH

Sol. In Ether

Extraction in ether
Aqueous Layer

Ether Layer

Psychotrine

Cephaeline

Extraction with CHCL3

Psychotrine

Evaporation

Cephaeline

Uses
Emetine & Cephaeline: decrease protein synthesis
So used as anti-tumor , anti-viral , anti-amoebic but too toxic for therapeutic use
Emetine & Psychotrine : Emetic drugs
Emetine HCL has irritant effect on stomach
Ipeca alk. Are diaphoretic , alone or in combination with opium
Crude drug is used as expectorant (due to Saponin)
Emetic HCL

Anti-amoebic (amoebic dysentery , fasciola)

5
`5

Dovers Powder

Curare alkaloids
Occurrence:
Chondrodendron to mentosum F. Menispermaceae
Certain strychnous extract
Curare contains : d-tubocurarine & curine (both are dimeric derived from Tyrosine)

Curine

Tubocurarine

Properties

d-tubocurarine: Freely sol. In H2O (4ry amm. Salt)

Insol. In ether & CHCL3 , Phenolic , (d-)alkaloid
it is bis-benzyle tetrahydroisoquinoline alk.

Curine (3ry alk.)

Water insol.

Optically active , Occurs in d- & l- forms

Isolation of curine & d-tubocurarine
Aq. Extract of curare + NH4OH gives:
1) Curine crystals
d-tubocuraine + alc. + H2S , Filter then add

2) F+ Ether , take the filtrate + HgCL2

ether

d-tubocuraine HCL

Tests for identification for d-tubocurarine

Green Color

Sat. solution (aq.) +FeCL3

Solution of alkaloidal HCl +
1) Na2CO3

Yellow brown PPT

2) Libermanns

Black Color

3) mandalins

Brown Color

4) Millons

Red Color

Uses
Tubocurarine HCL

Skeletal muscle relaxant

Used to control and decrease convulsions of strychnine poisoning

Used as diagnostic aid in Myasthenia gravis
6
`6

OPIUM ALKALOIDS
Occurrence:
Is air dried milky exudate or latex obtained by incising the mature unripe capsule of opium
poppy papaver somniferum F. Papaveraceae
More than 40 alkaloids were identified
Opium Alkaloid is usually occurs naturally combined with specific acid (Meconic Acid) or
other acids Sulfuric and acetic acid
Meconic Acid
Occurs only in Opium
Sol. In H2O , Sol. In Alc. &
Opium

H2O

H2O

Filter

Neutralization +CaCL2 or Pb acetate

Pb or Ca

meconic acid salt

Tests For identification
Meconic acid gives purplish red colored complex with FeCl3
Not readily destroyed by dil HCL
Unaffected by HgCL2
Classification of Opium Alkaloid
Benzyl isoquindine alk.

Papaverine & noscapine ( Narcotine )

Phenylethylamin Alk.
Phenanthrene Alk.

Narceine
Morphine , codeine & Thebaine

Opium Alkaloid of Isoquinoline group derived from tyrosine

A. Papaverine
Weak base , optically inactive , Can be extracted by CHCL3 from acidic solution,
Insol. In H2O , Sol. In CHCL3

Uses
1. Spasmolytic & vasodilator
, Used as anti-spasmodic for GIT spasms and bronchial asthma as papaverine HCL

 Color Tests
Warrens test: Papaverine + KMnO4 + Marquis reagent

Green Color

Blue

Papaverine + : not imp

1) Conc. H2SO4

Violet Color

2) Libermanns

Black Color

3) Mandalins

Grayish Green Color

Opium Alkaloids of Phenylethylamine Group

Narceine
1. Very Hygroscopic
2. Slightly sol. In H2O , sol. In ethanol , insol. In CHCL3
3. Is a weak monoacidic 3ry base

4. Can be extracted from aq. Solution of its salts By CHCL3

5. It contains both a C=O & COOH so forms hydrazone ,
Oxime , salts with NaHCO3
6. Weak monoacidic tertiary base
7. Not used medicinally
Narceine + :
1) Dil. H2SO4

Violet

Cherry red

Blue

Violet

Blue Color

2) I2

Opium Alkaloids of Phenanthrene Group All This alkaloids is strong basic

Morphine

Morphine

Codiene

Thebaine

1. Levorotatory , Insol. In H2O , Sparingly Sol in ethanol & CHCL3

2.It contains 2OH groups , one is phenolic at C-3 ( Gives Sol. Phenates with alkali )
2ry alcoholic at C-6

3.It pptates from acid solution by addition of NH4OH , NH4CL or (NH4)2SO4 Solutions
4.On methylation of phenolic OH group Gives Codiene
5.On heat with HCL gives apomorphine (Used as emetic)
6.On acetylation gives diacetyl morphine (Heroin)

 Uses
Narcotic analgesic in dose (5-20mg)

morphine HCL , sulfate , tartrate

Officially preparations containing morphine

1-Powdered Opium
2-Tincture Opium
3-Tincture Opii camphorata
Tests for identifications
For Phenolic Properties
1) + FeCL3

Blue color

2) Nitrous acid test : Solution of morphine in HCL + NaNO2 + NaOH

Red Color

Due to reducing properties

1) Morphine + Sucrose

+ Conc. H2SO4

Purple red color

2) Iodine Test: Solution of morphine + H2SO4 + CHCL3 +Iodic acid + I2

Structure activity relationship of morphine
Increase Activity Obtained By
a) Reduction / Methylation / Oxidation or Elimination of OH
b) OH gp at C-14
c) CH3 gp at C-5
d) Replacement of N- CH3 by other groups e.g. Phenylethyl gp
e) Acetylation

Heroin

Decrease Activity Obtained By

a) Methylation of phenolic OH
b) Opening of

Codiene

N-Containing Ring
4,5-Oxygen bridge

C) Dehydration by heat with HCL gives apomorphibe

d) Demethylation , N-CH3

N-H(Nor-morphine)

C6

Violet Color

Codiene
1. Sol. In H2O , CHCL3 & Ether
2. It dissolves in NH4OH due to formation of codeine amm hydroxide
3. Prepared from morphine by methylation of phenolic OH
4. It doesnt form Phenates
Tests for identifications
Codiene + Conc H2SO4 + FeCl3
Uses

warm
W.B

Bluish violet color + HNO3

1. Mild narcotic analgesics , less toxic than morphine

2. Less dangerous in habit formation
3. Mainly used as anti-tussive & sedative
Minimal Lethal dose 800 mg

Red Color

Opium
Addition of CaCl2
Maceration with water for 24 hrs

Filtration

Residue
Calciummeconate,
lactate&resinate

Filtrate
AlkaloidalHCl

AlkalinizationwithNaOH
Filteration

filtrate

Precipitate

Morphine,codeine&
Narceine

Papaverine,narcotine&
thebaine

ExtractionwithCHCl3
Chloroformlayer

Solubilizationindil.Alc.
Acidificationwithaceticacid

Aqueouslayer

Additionofboilingwater
Morphineasphenate&narcineasNasalt

Codeine

filtration

Acidification

PPT

filtrate

Alkalinizationwith
NH4OH

Concentration

filtrate

Alkalinizationwith
NH4OH

PPT

Thebaine

Narceine

Additionofwater+
oxalicacid
filtration

PPT
filtrate

Morphine

Papaverine

Narcotine

ALKALOIDS OF INDOLE GROUP

I. SEROTONIN & SEROTONIN DERIVATIVES :
Serotonin ( 5-hydroxy tryptamine ) :
metabolism

Skin irritant promoting histamine release " side effect of serotonin injection "
High conc. of 5-OH indole acetic acid ( metabolite of 5-OH tryptamine ) indicates the
presence of certain types of intestinal tumors and used for diagnosis
Occurance : is a mammalian neurohormone , the first report of isolation of serotonin
from plant origin was from Mucuna pruiens "Leguminoseae" , Also it is found in
several fruits e.g. banana, tomatos, avocado, eggplant & pinapple
Tests for identification :
1. + Marqui's gives brown colour
2. + Vitalis's test gives grayish green col then brown col.
3. + Amm. molybdate solution gives blue col. then brown col.
Serotonin derivatives :
5-methoxy-N,N-dimethyl-tryptamine (C)
5-hydroxy- N,N-dimethyl-tryptamine (b)

The principle hallucinogenic constituent of virola snuff , obtained from bark of

peptadenia peregrine (c)

Obtained from several sources including fungi of Amantina sp. (b)

II.

PSILOCIN , PSILOCYBIN RELATED ALKALOIDS :

Occurance : certain mushrooms , the red sacred mushroom of Mexico

Psilocybin

Psilocin

White crystals

Plates

Sol. in water

Insol. in water

Insol. in CHCl3

Sol. in alc. & a a'

On H3O it gives Psilocin +

Unstable in alkaline solution

Phosphoric a'

Upon phosphorylation gives

psilocybin

the only natural indole alk. that

contains phosphate radical

Tests of identification :
1. Marqui's reagent : + psilocin gives greenish brown col. WHILE + psilocybin gives
orange col.
2. Amm. molybdate : + psilocin gives greenish blue col. WHILE + psilocybin gives grey
colthen blue then green
3. Vitali's test + psilocin , gives brown or reddish brown
Uses :
both are hallucinogenic & narcotic alkaloids, they cause serious psychological

disturbances

III. CALA
ABAR BEAN
B
AL
LKALOIID : PH
HYSOST
TIGMA ALK
A
Physostigminee serine :
Occuraance : seedss of physosstigma ven
nenosum colabar beeans , fam. Leguminoosae

Properties :
- Sol.
S In alcoohol , CHCll3 & benzene
- Insol.
I
In peet. Ether

- 3ry base , posses

p
esterr linkage

- Eserine
E
by alk. H3O+ gives
g
eserooline + metthylamine + CO2
- Eserine
E
by oxidation in presencce of alkalii gives rub
beserine
- Eserine
E
cou
uld be affeected by thee alkalinityy of glass containers
c
during stoorage
Tests for identificaation :
ne blue tesst : eserine + conc. HN
NO3 gives yellowish red col wh
hich by evvaporation
1. Eserin
gives blluish residu
ue (Eserinee blue) sool. In alc.
2. Eserin
ne + NaOH
H or alkali hydroxidees give red
d col.
3. Eserin
ne + Mand
dalins reaggent give yellowish
y
b
brown
col.
4. Eserin
ne + K-ferrricyanide in
i presencce of tracess of FeCl3 give
g Prussian blue cool.
Uses :
1. Myottic drug
2. Has a cholinerg
gic effect and
a stimulaate glands secretion
3. Enhaance memoory especiaally in Alzeehiemers disease
d
so it
i acts as acetyl choliinesterase
inhibitoor Ach EI

IV. ERGOT ALKALOIDS :

Occurance : Ergot is the dried sclerotium of a fungus, claviceps purpurea fam.
Hypocreaceae that arises on the ovaries of rye plant cecale cereal fam. Gramineae
Ergot contains : large no. of alk. + nitrogenous bases + a a
Properties :
1. Have fluorescence under UV light
2. Ergot alk. Are N-monosubstituted amide derivatives of both lysergic a and its isomer
isolysergic a that didder only in conjugation at C-8
3. Ergot contains : 2 major alk. Divided into 6 pairs , acc. To their peptide moieties
4. Members related to :
a. Lysergic a : are levorotatory , suffix ine , e.g : ergotamine & ergometrine , more
active
b. Isolysergic a : are dextrorotatory , less active , suffix inine
** Isolysergic a members by reflux wz phosphoric a or acetic give lysergic a members
** Lysergic a members by reflux with alc. KOH give isolysergic a members
5. In badly stored aqueous solution, exposed to light or UV , are converted to Lumi
derivatives non-active

NH3

Ergine

Isoergine

Classification : Ergot alkaloids are classified into 3 gps acc. To hydrolytic products :
1. Ergometrine gp : yields 2 amino propanol
2. Ergotamine gp : yields pyruvic a CH3COCOOH
3. Ergotoxine gp : yields dimethyl pyruvic a
** LSD (Lysergic a diethylamide) is a synthetic cpd that has a very potent hallucinogenic
effect

 Tests for identificaation :

5% H2SO4 give deep
1. Van--Urks test : alk. Soluttion + Van-Urk reageent in pressence of 15
blue collour.
2. Kellerrs test : alk
k. Solution
n + acetic a
a in presen
nce of dps FeCl3 & coonc. H2SO4 give blue
layer
Estimatiion of Ergoot alkaloid
ds :
1. Colorrimetricallly : based on
o that thee blue col. Produced
P
w Van-Urks reaggent is
with
dependeent on con
nc. , the abssorbance is
i measureed at 590 nm
n and com
mpared wiith a std
referencce alk.
2. Fluorrometricallly : based on
o that thee alk. Are flluorescentt

A. Ergomet
E
trine Errgonovin
ne , Ergoobasine :
Colorlesss needles
Soluble in water
It has ad
dvantages over wateer insol. Erggot alk. In that it doeesnt produ
uce nauseaa &
vomitin
ng , moreovver, it possseses an ox
xytoxic activity
Upon H3O : 2-am
minopropan
nd + lyserggic acid
The offiicial salt : ergometrin
e
ne maleatee
Uses : caauses vigoourous con
ntraction off uterus , mainly
m
used as oxytoocic in ordeer to aid
deliveryy or to prevvent postp
partum hem
morrhage.

B. Ergotam
E
mine :
Decomp
poses on ex
xposure too air , heat & light
Insoluble in waterr , sol. In organic
o
solvvents
Monoaccidic base weak
Upon H3O : pyruvvic a + lyseergic a + D-proline
D
+ -phenyyl alanine
The offiicial salt : ergotamine
e
e tartaratee is unstablle in aqueoous solutioons and on exposure
to light

Uses : errgotaminee is mainly used as an

nalgesic in
n migraine

IV. NUX VOMICA ALKALOIDS STRYCHNOUS ALK. :

The dried ripe seeds of strychnous nux vomica fam. Loganiaceae
The major alkaloids are Strychnine & Brucine
Amount of strychnine ranges from 1/3 to of total alk.
Strychnine & Brucine are poisonous

They are dihydro-indole and quinoline derivatives

Strychnine

Brucine

- Sol. In alc. , CHCl3, benzene

- Sol. In alc. , CHCl3 , acetone

- Insol. In water & acetone

- Insol. In water

- Monoacidic base , dimethoxy strychnine

- Is a monoacidic base

Separation of a mixture of strychnine & brucine :

Strychnine can be separated from brucine by one of the following methods :
1. Mix. , shake with acetone brucine only dissolves
2. Mix. , shake with 25% ethanol . Brucine only dissolves
3. Mix. + K.ferrocyanide .. Strychnine ppt quickly & Brucine ppt slowly
4. Mix. + mix. Of conc. H2SO4 & HNO3 . Brucine destroyed.
Tests for identification :
1. Nitric a test :
- Strychnine crystals by HNO3 give faint yellow then by evap. Yellow
- Brucine crystals by HNO3 give intense red col. Then by evap. Wz SnCl2 give violet
2. H2SO4 / dichromate test : ( Only for Strychnine )
Strychnine crystals by H2SO4 & K2Cr2O7 crystals give blue streaks then violet then
purplish red then orange then yellow.
3. Mandalins reagent test : ( Only for Strychnine )
Strychnine + Mandalins give deep violet blue col. Then red then cherry red

 Uses :
a. Strychnine :
1. Used in vet. Medicines as a skeletal muscle relaxant and tonic
2. Used as antidote in barbiturate poisoning
3. Used as rodenticide & pesticide
N.B. : it is extremely toxic and it can be fatal to humans & animals it can occur
through : inhalation , swallowing , absorption through mouth or eye
Symptoms : nausea , vomiting then convulsions of all muscles , then spasms of facial
muscles causing cyanosis of the face , dilated pupil , prominent eye , frothing at mouth ,
the body may be seen arched shape .. then loss of consciousness then death due to
asphyxiation
b. Brucine : less toxic than Strychnine
1. Commercially used as alc. & oil denaturant

2. For separation of racemic mix. And as additive agent to lubricants

V. VINCA ALKALOIDS CATHARANTHUS ALK. :

Catharanthus or vinca is the dried whole plant of catharanthus roeus G. don (or vinca
rosea L) fam. Apocyanaceae
Contain about 90 alk. , most important : Vinblastine & Vincristine
They are dimeric alk. , have indole & dihydroindole nuclei
They differ in the presence of : N-methyl gp (Vinblastine) , N-formyl gp (Vincristine)
Vinblastine : Insol. In water , sol. In ethanol & CHCl3
Vincristine : occurs as crystals

Isolation : occurs in v.minute amounts in vinca , for pharmaceutical use, they are
prepared as sulfate salts and stored in sealed ampoules in a reftrigerator more stable
Tests for identification :
1. Vanillin/HCl reagent : pink (Vinblastine) & orange yellow (Vincristine)
2. Vinca alk. + Van-Urks + glacial a a + conc. H2SO4 give reddish brown col.

 Uses :
- Vinblastine : ttt of Hodgkins disease & carcinoma resistant to other therapy
- Vincristine : has cytotoxic effect so it is usefull in childhood leukemia , it is the main
component of several highly successful combination
Vinblastine by microbial transformation using streptomyces albogriseolus gives
Vincristine
Dose : 100g/kg of vinblastine SO4 weekly as I.V. infusion
25-25 g/kg of vincristine SO4 weekly as I.V. infusion

VI. RELATED SEMI-SYNTHETIC ALK. OF PHARMACEUTICAL IMP. :

1. Vinorelbine
Obtained from vinblastine by dehydration
Oral anti-cancer with broader activity
Low neurotoxicity than vincristine

2. Vindesine sulphate :
is amide of one of methylester gp derive. From vinblastine

It is used for ttt of lymphoid leukemia in children

ALKA
ALOIDS OF
O PURIINE GRO
OUP

Purrine

Tea leaves (caamellia

sineenis) F. Theeaceae

Cofffee beans (coffea

(

Arab
bica) F. Ru
ubiaceae
Cacoa seeds
(theeobroma caacoa) F.

Cafffeine

Th
heophylliine

Theobrromine

Present highest

Traces

Tracces

Present

Traces

Abseent

Presentt lowest

Absent

Pressent

Sterrculiaceae
Stru
ucture

Solu
ubility

Su
ublimate without
w
deecompositioon
Sol. In beenzene less

Insol. In benzene more polaar

poolar

Soll. In water
Basiicity
Alkaali hydroxide

S
Slightly
soll, in water

Weakk bases forrm salts with

w strong acids
Decoompose

S waterr
Sol.

Sol. Due to

enolizzation

NH4OH

Sol.

CHCl3

Sol.

Sol.

Insol.
Sparingly sol.

Uses

Smooth muscle
CNS stimulant &

relaxant ,

relieve headache

bronchodilator & has

Diuretic

also diuretic action

Mayers reagent

No ppt

Wagners reagent

Brown ppt

Tannic acid
Murexide test

White ppt dissolve in excess of reagent

-ve

Residue + conc HCl and (KClO3 or H2O2) by evaporation , gives red

color or changes to violet upon exposure to ammonia vapor

N.B. : Why is caffeine soluble in water ?? as it can form hydrogen bonds

Separation of purine group :
1. Extract the Mixture with benzene : caffeine will be separated in the benzene layer
2. Treat the mixture of (theophylline and theobromine) with ammonia : theophylline
will be dissolved in the ammonia solution while theobromide will be the residue.
Isolation of caffeine :
1. Extract with hot water , (caffeine + tannins + impurities) will be obtained
2. Treat the extract with Pb acetate , tannins & impurities will be ppt
3. Excess lead is removed by Na2HPO4
4. Extract with chloroform , caffeine will be obtained then crystallize from water.
Methylation pattern of Caffeine :
1. Enable caffeine to form hydrogen bonds so that it is water soluble and easily absorbed
2. Increase the lipid solubility so it can cross the blood brain barrier so it can exert its
central action . (C.f. theophylline and theobromine )

10

 Decaffeinated coffee :
Contain 1-5% caffeine of the original coffee beans
Caffeine stimulates gastric acid secretion (gastric ulcer) and is metabolized to uric acid
(cause gout)
Caffeine is removed either by :
1. Steaming then extraction with benzene (health hazard)
2. Extract the first patch with water (the common one)
- Remove caffeine from the aqueous extract
- Use the decaffeinated extract to remove caffeine from fresh patch of coffee beans
(repeat the cycle) . i.e. use decaffeinated coffee aqueous extract to remove caffeine
- OR use supercritical fluid carbon dioxide (the best , but expensive)

1stpatch
+water

Watersaturated
withcaffeineand
flavor

Removalof
caffeine

Watersaturated
withflavoronly

cycle
Subsequent
patches

11

Goforroasting
&processing

ALKALO
A
OIDS OF
F IMIDAZ
ZOLE GROUP
G
Occuraance : leavees of pilocaarpus japorrandi & other pilocaarpus sp. , ester
e
(interrnal
lactone)) of pilocarrpic a
Pilocarp
pine & isop
pilocarpinee are steriooisomers too each other (2/3 : 1//3)
Mono-aacidic basees , oily non
n volatile liquid
l
, Sool. In waterr , CHCl3 & ethanol and
a insol.
In petrooleum etheer
Lactonee ring is brroken by caaustic alkaalis & imidaazole ring is broken by KMnO4

Pilocarpine

Isolation
n:

Iso
oPilocarpin

Pilocarp
pica

1. Alkallinize the pd
p with Naa2CO3 (libeerate the frree base)
2. Extraact with beenzene (freee base in benzene)
b
3. Shakee benzene with acidiified waterr (pilocarp
pine migratte to aqueoous phase as salt , it
leaves behind
b
other impuritties)
4. Alkallinize the acidified
a
ex
xtract with
h NH3 (to liberate
l
thee free basee)
5. Extraact with CH
HCl3 (to takke the freee base, purre pilocarp
pine oil sol. In CHCL3)
6. Either evaporatte to get th
he oily free base or sh
hake with HCl
H and seeparate to crystallizee
drochloridee salt)
the hyd
Chemiccal test :
Helchs test : aq. Solution
S
+ 2-3
2 dps H2O2 + dil K2Cr2O7 an
nd then shaake with CHCl
C
3,
give vioolet col. In the organiic layer , (tthe aq. Layyer has yelllow to brown col. Deepending
on K2Crr2O7 conc.)
Determ
mination : by
b acid base titration & colorim
metry
Uses :
perties)
1. Myottic (cholineergic prop
2. Ttt off glaucomaa ( dec. intrraocular pressure)
p

3. In vet. Medicin
ne : stimulaate gastric secretions

12

DITERPINE ALKALOID : TAXOL

Occurance : bark of Yew tree (death tree) Taxus brevifolia , fam. Taxaceae

Mechanism of action & uses :

1. Broad spectrum anti-cancer, mainly in ovarian , lung and breast cancers
2. Binds to microtubules and stabilize them , so it prevents their depolarization and
ceases the cell mitosis.
Chemical synthesis : a lot of steps (large molecule, 11 stereocenters) , too expensive to
be applied in industrial field
Semi-synthesis :
-Tissue culture of Taxus baccata produces 10-deacetylbaccatin III (taxol (acetyl +
nitrogenous part))
-It is used as a starting material for synthesis of taxol and its derivative taxotere

Taxotere : water soluble , used in ovarian and breast cancer

Taxotere

13

STE
TEROIDA
AL ALKA
ALOIDS
S
Perhydrrocyclopen
ntano-phenanthrenee skeleton (sterol
(
nuccleus)
Found in
i glycosid
dal combin
nation so caalled glucooalkaloids
Commoon examplees : Solanu
um and Verratrum alkkaloids
Soluble in hot alcoohol and form
f
jelly upon
u
cooliing

Soolanine

Solason
nine (sollanocarp
pine)

S. nigru
um, S. tuberosum

S. aviculare,
a
S xanthocarpomum, S.
S.
sod
dmeum

Produceed by plants as they have

h
fungiicide & pessticide actiivities
Recent researches
r
s report an
nticancer activity
a
in vitro
v
as weell as in vivvo
Solason
nine is used
d as agricu
ultural inseecticide
The aglyycone : Sollanidine & Solasodin
ne can be used
u
as starrting material for syn
nthesis of
steroidaal drugs
Isolation
n of Solaniine :
Extract with acidiified waterr and evap
porate , then take the residue an
nd dissolvee in a a
and add
d NH3 , theen take thee ppt and dissolve
d
in ethanol an
nd heat then cool , Soolanine
will be obtained.
o

14

ALK
KALOID
DS OF TH
HE CAR
RBOLINE
E GROUP
P
Most off them act on CNS
Three examples :
mba alkalooids (Yohim
mbine) (ap
phrodisiac))
1. Yohim
2. Pegan
num (Harm
mine, Harm
maline) (haallucinogeenic)
3. Rauw
wolfia (Reseerpine) (in
n hyper ten
nsion & traanquilizerss)

Yohimbin
nOR
Aphrodine
Carboline
Bark of pausinystaalia yohim
mbe or coryyanthe yoh
himbe fam. Rubiaceaae
Uses : aphrodisiacc (male imp
potence , increase
i
seexual desirre)
N.B.. :
Pyriimidine + imidazole
i
------ purine
Lacttone + imid
dazole

-----piloocarpine

Indoole + pyrid
dine

------ carrboline

15