ALKALOIDS

PHARMACOGNOSY III
Third Year B. Pharm Sem V

By Mrs. V. J. Bhatia

VES College of Pharmacy, Chembur

1
 ALKALOIDS: INTRODUCTION

▪ A precise definition of the term ‘alkaloid’ (alkali-

like) is somewhat difficult because there is no
clear-cut boundary between alkaloids &
naturally occurring complex amines.

▪ Definition - Alkaloids are heterogeneous,

organic compounds of natural origin , they are
basic in nature, they contain one or more
nitrogen atom (usually in a heterocyclic ring) &
they have a marked physiological action in man
or animals when used in small concentration.
2
 CLASSIFICATION OF ALKALOIDS
 True Alkaloids –
 They normally contain nitrogen in the heterocyclic ring.

 Originate from amino acids

 Normally they occur in the plant as a salts of organic acids

e.g Meconic acid, aconic acid, Cinnamic acid.

 Basic in nature.

 E.g Opium (Morphine), Belladonna (Atropine)

3
MORPHINE

4
CLASSIFICATION OF ALKALOIDS
 Proto alkaloids – They are simple amines or
biological amines.
 The amino acid nitrogen atom is not in a
heterocyclic ring.
 Originate from amino acids
 They are basic in nature e.g
 Ephedra (Ephedrine)
5
 Colchicum (Colchicine)
EPHEDRINE

6
CLASSIFICATION OF ALKALOIDS
• Pseudoalkaloids

• Contains nitrogen in the heterocyclic ring

• Weakly basic in nature

• They are not derived from amino acid

• Do not show many of the typical characters of

alkaloids.

• Give give the standard qualitative tests for

7
alkaloids.
PSEUDOALKALOIDS
• E.g Purine bases

• Tea, Coffee (Caffeine, Theobromine, Theophylline),

• Steroidal alkaloids

Veratrum

Ashwagandha (Withanolide)

Kurchi (Conessine)

• Terpenoid alkaloid

Aconitine (Aconitine, Aconine) 8

CONNESSINE

9
CAFFEINE

10
ALKALOIDS

11
ALKALOIDS: HISTORY
▪ The term alkaloid was coined by Meissner, a German
pharmacist in 1819

▪ The first isolation of alkaloids in the nineteenth century

followed the reintroduction in to medicine of a number of
alkaloid-containing drugs.

▪ The French apothecary Derosane probably isolated the

alkaloid afterwards known as narcotine in 1803

▪ Serturner further investigated opium & isolated

morphine (1806, 1816).
12
ALKALOIDS: HISTORY
 Isolation of other alkaloids, particularly by
Pelletier & Caventou, rapidly followed;
strychnine (1817), emetine (1817), brucine
(1819), piperine(1819), caffeine (1819), quinine
(1820), colchicine (1820) & coniine (1826)

▪ Coniine was the first alkaloid to have its

structure established (Schiff, 1870) & to be
synthesized (Ladenburg, 1889), but for others,
such as colchicine, it was well over a century13
before the structures were finally elucidated.
ALKALOIDS:
OCCURRENCE/DISTRIBUTION
▪ Major distribution of alkaloids occurs in angiosperms

▪ True Alkaloids are of rare occurrence in lower plants.

▪ In the fungi, the lysergic acid derivatives and the sulphur-

containing alkaloids, e.g. the gliotoxins, are the best
known.
▪ Among the Pteridophytes and gymnosperms the
lycopodium, ephedra and Taxus alkaloids have medicinal
interest.
▪ Alkaloid distribution in the Angiosperms is uneven. 14
 ALKALOIDS:
OCCURRENCE/DISTRIBUTION
Alkaloids are commonly found in the orders:-
▪ Centrospermae (Chenopodiaceae), Magnoliales (Lauraceae,
Magnoliaceae),

▪ Renanculales (Berberidaceae, Menispermaceae, Rananculaceae),

▪ Papaverales (Papaveraceae, Fumariaceae),

▪ Rosales (Leguminosae, subfamily Papilionaceae),

▪ Rutales (Rutaceae),

▪ Gentiales (Apocynaceae, Loganiaceae, Rubiaceae),

▪ Tubiflorae (Boraginaceae, Convolvulaceae, Solanaceae) and

▪ Campanulales (Campanulaceae, sub-family Lobelioideae; Compositae,
15
subfamily Senecioneae).
 ALKALOIDS:
OCCURRENCE/DISTRIBUTION
Within a plant in most of the cases, the alkaloids
are highly localized and concentrated in certain
morphological parts only
e.g Seeds (Nux vomica),
Roots (Rauvolfia, Belladonna, Ashwagandha),
Bark (Kurchi, Cinchona),
Leaves (Senna, Vasaka, Datura, Vinca),
16
Stem –Ephedra.
ALKALOIDS: PHYSICAL PROPERTIES
▪ Most Alkaloids are well-defined crystalline substances,
some are amorphous which unite with acids to form salts.
▪ In the plants they may exist in the free state, as salts or as
N-oxides.
▪ In addition to the elements carbon, hydrogen and nitrogen,
most alkaloids contain oxygen.
▪ A few, such as coniine from hemlock & nicotine from tobacco,
are oxygen-free and are liquids.
▪ Although coloured alkaloids are relatively rare, they are not
unknown; berberine, for example, is yellow and the salts of
17
sanguinarine are copper-red.
 ALKALOIDS: PHYSICAL PROPERTIES
▪ The solubilities of different alkaloids and salts shows
considerable variation, because of their extremely varied
structure.
▪ The free bases are frequently sparingly soluble in
water, but soluble in organic solvents.
▪ With salts the reverse is often the case, these being
usually soluble in water but sparingly soluble in
organic solvents.
▪ For e.g. strychnine hydrochloride is much more soluble in
water than is strychnine base. 18
ALKALOIDS: PHYSICAL PROPERTIES
▪ But there are many exceptions to the above
generalizations.

▪ Proto alkaloids and Pseudo alkaloids are more

soluble than true alkaloids.

▪ Caffeine (base) being readily extracted from tea

with water and colchicine being soluble in either
acid, neutral or alkaline water.
19
ALKALOIDS: CHEMICAL PROPERTIES
 Most of the alkaloids are basic in reaction due
to availability of lone pair of electrons on
nitrogen.

 The basic character of alkaloidal compound is

enhanced if the adjacent functional groups are
electron releasing.

20
ALKALOIDS: CHEMICAL PROPERTIES

 The alkaloid turns to be acidic or neutral when the

adjacent functional groups are electron withdrawing
which reduces the availability of lone pair of
electrons.

21
ALKALOIDS: CHEMICAL PROPERTIES
 The alkaloids may contain one or more number
of nitrogen
 It may exist as

 Primary amine – RNH2 e.g mescaline.

 Secondary amine – R2NH, Ephedrine

 Tertiary amine – R3N, Atropine

 Quaternary ammonium compound – R4N+
Tubocurarine chloride

22
 CHEMICAL TESTS FOR ALKALOIDS
Name of Reagent Observation
Mayer’s reagent (Potassium Cream coloured
mercuric iodide solution) precipitate

Wagner’s reagent (Solution of Reddish brown

Iodine in Potassium iodide) coloured precipitate

Hager’s reagent (Saturated Yellow coloured

solution of picric acid) precipitate

Dragendorff’s reagent (Solution Reddish yellow

of Potassium bismuth iodide) coloured precipitate
23
 ISOLATION OF ALKALOIDS
▪ Extraction of alkaloids from plants is generally an easier
process but it largely depends upon large or small scale
operations, & the type & purity of alkaloid to be
separated.

▪ Two processes can be generalized for the isolation of

alkaloids.

1. Stass Otto process

2. Manske’s process 24
 • In this process, powdered crude drug is
first defatted with petroleum ether to
remove any fatty material, pigments or
Defatting other unwanted material. (but before
defatting, check the solubility of
alkaloid in the petroleum ether)

• Then drug material is moistened with water

Treatment & thoroughly treated with alkali (Ammonia,
with Sodium carbonate, Calcium hydroxide

Alkali (lime) which liberates alkaloidal free bases

from their acid

25
NH4OH:
Most widely used due to many advantages:
1- Strong enough to liberate most of alkaloids from
their salts.
2- Milder than fixed alkalis so more safe.
3- Volatile

Other Alkalis:
Na2CO3, NaHCO3, Ca(OH)2, MgO.
ALKALOIDS
MANSKE’S PROCESS

▪ In this process, powdered crude drug is first

defatted with Petroleum ether to remove any
fatty material, pigments or other unwanted
material. (but before defatting, check the
solubility of alkaloid in the petroleum ether)

▪ The residue is further extracted with

methyl/Ethyl alcohol to isolate alkaloid from
28
that of cellular material.
MANSKE’S PROCESS
▪ The alcoholic extract is concentrated,
dissolved in water acidified to pH 2 and further
steam distilled to remove traces of alcohol.

▪ The dark solution is allowed to stand for several

days in refrigerator or heated with paraffin to
remove impurities.

29
ALKALOIDS
MANSKE’S PROCESS

▪ The filtrate is extracted with ether or chloroform to

remove non alkaloidal organic matter.

▪ The resultant solution is basified & again extracted with

ether or chloroform. The organic layer obtained is
evaporated to yield crude alkaloid.

31
 PURIFICATION OF ALKALOIDS
▪ The crude alkaloid may contain several groups of alkaloids & it
is further purified in to individual alkaloids by column
chromatographic fractionation, counter current extraction,
fractional crystallization, fractional precipitation or by any
other suitable procedure.
▪ Chromatographic methods are particularly suitable if the
mixture is a complex one & small quantities of alkaloids are
present.
▪ Supercritical fluid extraction can also be used for carrying out
the process of extraction. 32
FUNCTIONS
 Produce varying degrees of physiological and psychological
responses - largely by interfering with neurotransmitters.

 Others interfere with membrane transport, protein synthesis or

other processes

 In large doses - highly toxic – fatal

 In small doses, many have therapeutic value

 Muscle relaxants, tranquilizers, Analgesics , Expectorants,

Antitussives, Antimalarials, Anticancer, Oxytocic, Sedatives etc
33
FUNCTIONS OF ALKALOIDS IN PLANTS
▪ They are the reserve substances with an ability to supply
nitrogen.
▪ In some cases the alkaloids could provide either a means
of storing or transporting in soluble form the particular
acids.
▪ In the case of solanaceous plants tropane esters formed in
the roots are translocated to the aerial parts, where
hydrolysis of the alkaloid and breakdown of the liberated
acid occurs.
34
FUNCTIONS OF ALKALOIDS IN
PLANTS
• It is also possible that they are the end products of
detoxification mechanism in plants and they check the
formation of substances which may prove to be harmful in the
plants.
• Alkaloids may have a role in the defense of the plant
against singlet oxygen (1O2), which is damaging to all
living organisms and is produced in plant tissues in the
presence of light.
• of 15 alkaloids tested, most showed a good ability to quench
singlet oxygen, with brucine and strychnine being
35
especially efficient.
ALKALOIDS: CLASSIFICATION

The various methods proposed for the classification of

Alkaloids are as follows:

1) Pharmacological Classification

2) Taxonomic Classification

3) Biosynthetic Classification

4) Chemical Classification
36
PHARMACOLOGICAL CLASSIFICATION
▪ Depending on the physiological response, the alkaloids are
classified under various pharmacological categories, like
central nervous system stimulants or depressants,
sympathomimetics, analgesics, purgatives, etc.
▪ This method does not take into account chemical nature of
crude drugs.
▪ Within the same drug, the individual alkaloid (Opium) may
exhibit different action e.g. morphine is narcotic analgesic,
while codeine is mainly antitussive.
▪ In cinchona, quinine is antimalarial, while quinidine 37
is
cardiac depressant.
LIST OF CRUDE DRUGS CONTAINING ALKALOIDS OF
SPECIFIC USES
Uses Alkaloids
Oxytocic Ergot (Ergotamine, Ergometrine)
Hypotensive, Rauwolfia (Reserpine)
tranquilizer
Anticancer Vinca (Vincristine, Vinblastin) , Taxus
(Taxol)
Narcotic Analgesic Raw Opium (Morphine, Codeine)
Skeletal Muscle Curare
Relaxant
Emetic Ipecacunha (Emetine)
Anticholinergic Belladonna, Datura, Hyoscyamus,
Stramonium
(Atropine, Hyosine, Hyoscymine)
Local anaesthetic Coca 38

Respiratory Stimulant Lobelia (Lobeline)

 TAXONOMIC CLASSIFICATION
▪ This method classifies the vast number of alkaloids
based on their distribution in various plant families,
like solanaceous or papillionaceous alkaloids.
▪ E.g Atropine, Hyoscine, Hyoscymine

▪ Preferably, they are grouped as per the name of the

genus in which they occur, e.g. ephedra, cinchona, etc.

39
BIOSYNTHETIC CLASSIFICATION

▪ This method gives significance to the precursor from

which the alkaloids are biosynthesized in the plant.

▪ Hence, the variety of alkaloids with different taxonomic

distribution and physiological activities can be brought
under same group, if they are derived from the same
precursor. E.g. all Indole alkaloids from tryptophan are
grouped together.

▪ The alkaloidal drugs are categorised on the fact whether

they are derived from amino acid precursor as ornithine,
lysine, tyrosine, phenylalanine, tryptophan, etc. 40
BIOSYNTHETIC CLASSIFICATION

41
CHEMICAL CLASSIFICATION

▪ This is the most accepted way of classification of alkaloids.

▪ The main criterion for chemical classification is the type of

fundamental (normally heterocyclic) ring structure
present in alkaloid. The alkaloidal drugs are broadly
categorised into two divisions:-

I Non-heterocyclic or atypical alkaloids, sometimes

called ‘Protoalkaloids’ or biological amines.

II Heterocyclic or typical alkaloids, divided into 14 groups

42

according to their ring structure.

 http://t0.gstatic.com/images?q=tbn:Co_wqj0QTU-LeM:http://upload.wikimedia.org/wikipedia/commons/3/38/Purine.png

Tropane Purine

Imidazole QUINOLINE
Pyrrolid
http://t0.gstatic.com/images?q=tbn:9X0Q4zIyovF0XM:http://upload.wikimedia.org/wikipedia/commons/thumb/a/ae/Indolizidine.svg/120px-Indolizidine.svg.png
ine

Indole Indolizidi
ne 43
http://t0.gstatic.com/images?q=tbn:0xaYqxeCkZXMqM:http://upload.wikimedia.org/wikipedia/commons/thumb/c/c2/Quinolizidine.svg/200px-Quinolizidine.svg.png

http://t0.gstatic.com/images?q=tbn:oQBUJNPsZYdCTM:http://www.chem.qmul.ac.uk/iupac/sectionF/alkgif/alk5.gif

Norlupinane
http://t3.gstatic.com/images?q=tbn:Hcrrp9ZSW1B6bM:http://www.shaman-australis.com.au/Website/law/Piperazine/pics/piperidine.gif

Aporphine

Piperidine 44

Isoquinoline
 TYPES OF ALKALOID AND THEIR OCCURENCE
Non heterocyclic or a Occurence
typical alkaloids

Hordenine or In germinating barley, Hordeum

N-methyltyramine distochon

Mescaline, related Lophora williamsii

to tryptamine (Cactaceae)

45
 TYPES OF ALKALOID AND THEIR OCCURENCE

Non heterocyclic or a Occurence

typical alkaloids
Ephedrine Ephedra spp.
(Ephedraceae)

Colchicine (tropolone nucleus Colchicum spp. & related

with nitrogen in side chain) genera (Liliaceae)

46
TYPES OF ALKALOID AND THEIR OCCURENCE
Non heterocyclic or a typical Occurence
alkaloids

Jurubin (steroid with 3- Solanum paniculatum

amino group) (Solanaceae)

Pachysandrine A (steroid Pachysandra terminalis

with N-containing C-17 side (Buxaceae)
chain)
Taxol (a modified diterpene Taxus brevifolia
pseudoalkaloid) (Taxaceae)

47
TYPES OF ALKALOID AND THEIR OCCURENCE
Heterocyclic or typical Occurence
alkaloids

1. Pyrrole & pyrrolidine

Pyrrolidine
Hygrine Cocoa spp. (Erythroxylaceae);

2. Pyrrolizidine
Senecionine, seneciphylline, Senecio
etc. spp.

Pyrrolizidine 48
 TYPES OF ALKALOID AND THEIR OCCURENCE http://t3.gstatic.com/images?q=tbn:Hcrrp9ZSW1B6bM:http://www.shaman-australis.com.au/Website/law/Piperazine/pics/piperidine.gif

Heterocyclic or typical Occurence

alkaloids
3. Pyridine & Piperidine
Piperidine

Trigonelline Fenugreek (Leguminosae),

strophanthus (Apocynaceae), coffee
(Rubiaceae)
Coniine Conium maculatum (Umbelliferae)
Arecoline Areca catechu (Palmae)
Lobeline Lobelia spp. (Lobeliaceae)
Nicotine (pyridine + Nicotiana tabacum & other spp.
pyrrolidine) (Solanaceae)
Anabasine Nicotiana glauca; Anabasis aphylla
49

(Chenopodiaceae)
Piperine Piper spp. (Piperaceae)
 TYPES OF ALKALOID AND THEIR OCCURENCE
Heterocyclic or typical Occurence
alkaloids
4. Tropane
(piperidine/N-methyl- Pyrrolidi Tropane
pyrrolidine) ne
Hyoscyamine, atropine, Species of Atropa, Datura,
hyoscine Hyoscyamus (Solanaceae)

Cocaine Coca spp. (Erythroxylaceae)

5. Quinoline
Quinine, quinidine,
cinchonine, Cinchona spp. (Rubiaceae),
50

cinchonidine Remijia spp. (Rubiaceae)

 TYPES OF ALKALOID AND THEIR OCCURENCE
Heterocyclic or typical Occurence
alkaloids

6. Isoquinoline Isoquinoline
Papaverine, Papaver somniferum
narceine, (Papaveraceae)
narcotine
Hydrastine, Berberine Berberis aristata and Numerous
genera of the Berberidaceae,
Ranunculaceae & Papaveraceae
Emetine, Cephaline Cephaelis spp. (Rubiaceae)
Ipecacuanha
51

Tubocurarine Curare obtained from plants of

Menispermaceae
 TYPES OF ALKALOID AND THEIR OCCURENCE http://t0.gstatic.com/images?q=tbn:oQBUJNPsZYdCTM:http://www.chem.qmul.ac.uk/iupac/sectionF/alkgif/alk5.gif

Heterocyclic or typical Occurence

alkaloids
7. Aporphine (reduced
isoquinoline/napthale
ne) Aporphine

Boldine Peumus boldus (Monimiaceae)

8. Norlupinane
Sparteine, cytisine, Sometimes called ‘ the lupin
lupanine, laburnine alkaloids’. Occur particularly in
http://t0.gstatic.com/images?q=tbn:0xaYqxeCkZXMqM:http://upload.wikimedia.org/wikipedia/commons/thumb/c/c2/Quinolizidine.svg/200px-Quinolizidine.svg.png

the Leguminosae, subfamily

Papilionaceae, e.g. broom.
52
Norlupinane Cytisus scoparius; dyer’s
broom, Genista tinctoria;
TYPES OF ALKALOID AND THEIR OCCURENCE
Heterocyclic or typical Occurence
alkaloids

9. Indole or benzopyrrole
Indole
Ergometrine, Ergotamine Ergot, Claviceps spp. (Hypocreaceae)
Physostigmine Physostigma venenosum
(Leguminosae)
Ajmaline, serpentine, Rauwolfia spp. (Apocynaceae)
reserpine
Yohimbine, aspidospermine Aspidosperma spp. (Apocynaceae)
Vinblastine , Vincristine Vinca (Catharanthus roseus)
(Apocynaceae)
Calabash curare alkaloids Strychnos spp. (Loganiaceae)
Strychnine, Brucine Strychnos spp. (Loganiaceae) 53
 TYPES OF ALKALOID AND THEIR OCCURENCE
Heterocyclic or typical Occurence
http://t0.gstatic.com/images?q=tbn:9X0Q4zIyovF0XM:http://upload.wikimedia.org/wikipedia/commons/thumb/a/ae/Indolizidine.svg/120px-Indolizidine.svg.png

alkaloids
10. Indolizidine
Castanospermine Castanospermum Indolizidine
australe (Leguminosae),
Alexa spp. (Leguminosae)

11. Imidazole or glyoxaline

Imidazole

Pilocarpine, Iso pilocarpine Pilocarpus spp. (Rutaceae)

12.Purine http://t0.gstatic.com/images?q=tbn:Co_wqj0QTU-LeM:http://upload.wikimedia.org/wikipedia/commons/3/38/Purine.png

(pyrimidine/imidazole)
Purine
Caffeine Tea (Ternstroemiaceae),coffee(Rubiaceae),
cola nuts (Sterculiaceae). 54

Theobromine Cocoa (Sterculiaceae).

 TYPES OF ALKALOID AND THEIR OCCURENCE
Heterocyclic or typical Occurence
alkaloids
11. Phenanthrene alkaloid

Morphine, Codeine Opium (Papaver somniferum)

12. Quinazoline

Vasicine, Vascinone Vasaka (Adhatoda vasica) Family

Acanthaceae
55
TYPES OF ALKALOID AND THEIR OCCURENCE
Heterocyclic or typical Occurence
alkaloids

13. Steroidal (some

combined as glycosides)
Solanidine (glycoside = Shoots of potato (Solanaceae)
solanine)
Veratrum alkamine esters Veratrum spp
& their glycosides
Conessine Holarrhena antidysenterica
(Apocynaceae)
14. Terpenoid
(Diterpene)
56
Aconitine, Aconine Aconite
LIST OF CRUDE DRUGS CONTAINING ALKALOIDS AS
ACTIVE CONSTITUENTS
INDOLE ALKALOIDS
Name of drug Biological Source Active Uses
& Synonym Constituents
Rauwolfia Roots & rhizomes Hypotensive
(Sarpagandha of Rauwolfia Reserpine, tranquilizer
) serpentina, rescinnamin
Apocynaceae e
Vinca Entire plant of Vincristine, Anticancer
(Catharanthu Catharanthus Vinblastine (treatment of
s) roseus, Hodgkin’s
Apocynaceae disease &
leukemia)

57
LIST OF CRUDE DRUGS CONTAINING ALKALOIDS AS
ACTIVE CONSTITUENTS
TROPANE ALKALOIDS

Name of drug Biological Active Uses

& Synonym Source Constituents
Belladonna Dried leaves & L- Anticholinergi
(Deadly night flowering tops hyoscyamine c,
shade Leaf) of Atropa , atropine antispasmodic
belladonna,
Solanaceae

58