Alkaloids.pTYHN BCDETJN CVTEN TY6NYRBTSHJ

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1. School of Pharmaceutical Sciences
Pharmacognosy and Phytochemistry II (BP504T)
By:
Prof. Ajay Sharma

2. General introduction, composition, chemistry & chemical
classes, biosources, therapeutic uses and commercial
applications of following secondary metabolites:
Alkaloids: Vinca, Rauwolfia, Belladonna, Opium
Phenylpropanoids and Flavonoids: Lignans, Tea, Ruta
Steroids, Cardiac Glycosides & Triterpenoids: Liquorice,
Dioscorea, Digitalis
UNIT-II 14 Hours

3. Volatile oils: Mentha, Clove, Cinnamon, Fennel, Coriander
Tannins: Catechu, Pterocarpus
Resins: Benzoin, Guggul, Ginger, Asafoetida, Myrrh,
Colophony
Glycosides: Senna, Aloes, Bitter Almond
Iridoids, Other terpenoids & Naphthaquinones:
Gentian, Artemisia, Taxus, Carotenoids

4. Alkaloids
Alkaloids are basic, nitrogenous, organic compounds
obtained from plants (few from fungi, and marine
organisms) and are physiologically active.
Most, but not all, alkaloids shows basic nature due to the
presence of amino group.
Derived from amino acids (Ornithine: Tropane Alkaloids;
Tryptophan: Nux Vomica, Catharanthus, Ergot and
Rauwolfia alkaloids)
They are bitter in taste with limited distribution in nature
4

5. Alkaloids form double salts with mercury, gold, platinum
and other heavy metals. These salts are obtained as
precipitate which are microcrystallographic.
Alkaloids usually contain one nitrogen atom (Ergotamine
contains 5 nitrogen atoms).
The N-atom may exist as primary amine (RNH
2
), secondary
amine (R
2
NH), tertiary (R
3
N) or quaternary amine (R
4
N
+
).
5

6. Precise definition: 'alkaloid' (alkali-like) is somewhat
difficult because there is no clear-cut boundary between
alkaloids and naturally occurring complex amines.
Typically, alkaloids are derived from plant sources, they
are basic, contains one or more nitrogen atoms
(heterocyclic ring) and they usually have a
marked physiological action on man or other animals.

7. The name 'proto-alkaloid' or 'amino-alkaloid' such as
hordenine, ephedrine and colchicine lack one or more
properties of typical alkaloids.
General formula of Alkaloids
7

8. Properties of Alkaloids
Most are crystalline but few are amorphous.
Free alkaloids are insoluble or sparingly soluble in water
but their salts are freely soluble.
Free alkaloids are soluble in ether, chloroform, benzene,
acetone, methanol or other relatively non-polar solvents.
Alkaloids are weak bases. Codeine has strongest while,
caffeine has weakest basic properties
8

9. The degree of basicity varies greatly, depending on the
structure of the molecule and the presence and location
of other functional groups.
The basicity of alkaloids depends on the availability of
lone pair of electrons on N- atom:
1.Electron-withdrawing groups in close proximity to the
nitrogen atom decrease the basicity
2.Electron-donating groups enhance the basicity.
9

10. Most alkaloids are crystalline substances which unite with
acids to form salts.
In plant, they may exist in free state/salts/N-oxides.
In addition to carbon, hydrogen and nitrogen, most
alkaloids contain oxygen.
Some alkaloids are liquid because of lacking of oxygen in
their molecules (coniine, nicotine, spartenine)
Colored alkaloids are very rare. Ex., Berberine is yellow
and Sanguinarine is copper-red.
Have high melting points
10

11. The basic character of heterocyclic ring varies:
In pyridine (6-electrons), quinoline and isoquinoline,
the lone pair of electrons on the N-atom is available
which imparts basicity.
11

12. In the case of pyrrole or indole, the lone pair of electrons
on the nitrogen atom plays a role in the aromatic
character, and the compounds are not basic (they are
acidic).
Pyrrolidine is saturated and is a strong base.
Pyrrolidine: Basic
12
Acidic

13. Primary amine
Basic
Secondary amine
Basic
+ OCH
3
Tertiary amine
Basic
Quaternary amine
Neutral
Amide alkaloid
Neutral
Phenol alkaloid
Acidic & basic
13

14. Types and Occurrence of Alkaloids
TRUE PROTOALKALOIDS PSEUDOALKALOIDS
Derived from
amino acids
Derived from simple
amines
NOT derived from amino
acids
Basic in NatureBasic in Nature Very weak basicity
N atom in
heterocyclic ring
N atom not in
heterocyclic ring
N atom in heterocyclic
ring or not
Atropine,
Morphine
Mescaline, Ephedrine,
Hordenine, Colchicine
Caffeine
14

15. Types Occurrence
A. Non-heterocyclic
Hordenine/
N-methyltyramine
Germinating Barley, Hordeum
distochon
Mescaline Lophophora williamsii (Cactaceae)
Ephedrine Ephedra (Ephedraceae)
Colchicine Colchicum sp (Liliaceae)
Erythromycin Streptomyces erythreus
(Bacteriophyta, Actinomycetales)
Jurubin Solanum paniculatum (Solanaceae)
Pachysandrine A Pachysandra terminalis (Buxaceae)
Taxol Taxus brevifolia (Taxaceae)
15

16. 16
B. Heterocyclic
1. Pyrrole & Pyrrolidine
Hygrine Coca sp (Erythroxylaceae)
Stachydrine Stachys tuberifera (Labiatae),
Soyabean and other Leguminosae
2. Pyrrolizidine
Symphitine, echimidine Symphytum spp.
Senecionine, seneciphyllineSenecio spp.
3. Pyridine & piperidine
Trigonelline Fenugreek (Leguminosae),
Strophanthus (Apocynaceae),
Coffee (Rubiaceae)
Coniine Conium maculatum (Umbelliferae)

17. 17
B. Heterocyclic
Arecoline Areca catechu (Palmae)
Lobeline Lobelia spp. (Lobeliaceae)
PelletierinePunica granatum (Punicaceae)
Nicotine
(pyridine +
pyrrolidine)
Nicotiana tabaccum (Solanaceae)
Anabasine Nicotiana glauca; Anabasis aphylla
(Chenopodiaceae)
Piperine Piper spp. (Piperaceae)
Ricinine Ricinus communis (Euphorbiaceae)

18. 18
B. Heterocyclic
4. Tropane (piperidine/ N-methyl-pyrrolidine)
Hyoscyamine,
atropine, hyoscine,
meteloidine
Atropa sp., Datura, Hyoscyamus,
Duboisia, Mandragora and Scopolia
(Solanaceae)
Calystegines Convolvulus spp., Ipomoea polpha
(Convolvulaceae), some solanaceous
spp., Morus spp. (Moraceae)
Cocaine Coca spp. (Erythroxylaceae
Pesudo-
pelletierine
Punica granatum (Punicaceae)

19. 19
B. Heterocyclic
5. Quinoline
Quinine, quinidine,
cinchonine, cinchonidine
Cinchona sp. (Rubiaceae),
Remijia sp. (Rubiaceae
Cusparine Angostura or Cusparia bark,
Galipea officinalis (Rutaceae)
6. Isoquinoline
Papaverine, narceine,
narcotine
Papaver somniferum
(Papaveraceae)
Corydaline Corydalis and Dicentra spp.
(Fumariaceae)
Hydrastine, berberineBerberidaceae, Ranunculaceae,
Papaveraceae

20. 20
B. Heterocyclic
Emetine,
Cephaeline
Cephaelis spp. (Rubiaceae)
TubocurarineCurare (Menispermaceae)
Morphine,
codeine
Papaver somniferum (Papaveraceae
ErythralineErythrina spp. (Leguminosae)
GalanthamineLeucojum aestivum (Amaryllidaceae)
7. Aporphine (reduced isoquinoline/naphthalene
Boldine Peumus boldus (Monimiaceae)

21. 21
B. Heterocyclic
8. Quinolizidine (Lupane alkaloids)
Sparteine, cytisine,
lupanine, laburnine
Leguminosae, subfamily
Papilionaceae, e.g. broom. Cytisus
scoparius; Dyer’s broom, Genista
tinctoria; Laburnum and Lupinus
spp.
9. Indole (Benzopyrrole alkaloids)
Ergometrine,
ergotamine
Claviceps sp (Hypocreaceae)
Lysergic acid amide,
clavine alkaloids
Rivea corymbosa, Ipomoea
violacea (Convolvulaceae

22. 22
B. Heterocyclic
PhysostigminePhysostigma venenosum
(Leguminosae)
Ajmaline,
serpentine,
reserpine
Rauwolfia sp. (Apocynaceae)
Yohimbine,
aspidospermine
Aspidosperma sp. (Apocynaceae)
Vinblastine,
vincristine
Catharanthus roseus (Apocynaceae)
Calabash, Curare
alkaloids
Strychnos sp. (Loganiaceae)
Strychnine, brucineStrychnos sp. (Loganiaceae)

23. 23
10. Indolizidine
CastanospermineCastanospermum australe
(Leguminosae),
Alexa sp. (Leguminosae)
Swainsonine Swainsona sp. (Leguminosae), Loco
plants (Leguminosae)
11. Imidazole or glyoxaline
PilocarpinePilocarpus sp. (Rutaceae)
12. Purine
Caffeine Tea (Ternstroemiaceae), Coffee
(Rubiaceae), Mate (Aquifoliaceae),
Guarana (Sapindaceae), Cola nuts
(Sterculiaceae)

24. B. Heterocyclic
13. Steroidal (some combined as glycosides)
Solanidine Shoots of potato (Solanaceae)
Veratrum Veratrum sp. and Schoenocaulon
sp. (Liliaceae)
Conessine Holarrhena antidysenterica
(Apocynaceae)
Funtumine Funtumia elastica (Apocynaceae)
14. Terpenoid
Aconitine, atisine,
lyctonine etc.
Aconitum and Delphinium sp.
(Ranunculaceae)
24

25. Nomenclature of Alkaloids
From generic name: Hydrastine, atropine
From species name: Cocaine, Belladonnine
Common name: Ergotamine
Physiologic activity: Emetine, morphine
From the discoverer: Pelletierine
All names of alkaloids should end with “-ine”.
A prefix or suffix is added to the name of principal alkaloid
from the same source (quinine, quinidine, hydroquinine)
25

26. 26
Functions
Regulatory growth factors
Plant protection against insects and herbivores because
of its poisonous nature
End products of detoxification reactions representing
metabolic locking up of compounds, otherwise harmful
to the plants.
Reserve substance that supply nitrogen or other elements
necessary to plant’s economy

27. Extraction & Isolation of Alkaloids
Alkaloids can be extracted by following two methods:
1.Direct extraction using non-polar organic solvent
2.Extraction using polar solvent
27

28. 1.Direct extraction using non-polar organic solvent (Stass
Otto method):
The powdered material is moistened with lime water,
which combines with acids, tannins and other phenolic
substances and set free the alkaloid base (Exist in the
plant as salt).
The extraction is then carried out with organic solvent
such as ether or chloroform, filtered and concentrate
the filtrate.
28

29. The concentrated organic extract is then shaken with aqueous
acid solution to form alkaloidal salts, which are soluble in
aqueous acidic layer. The impurities present in the extract
remain in the organic liquid.
The aqueous acidic phase is separated and alkaloidal salts
present are precipitated using strong ammonia solution.
Precipitated alkaloidal bases are batch extracted with
chloroform or ether and evaporated to dryness.
The dry residue is weighed, which gives total alkaloidal content
of the drug.
29

31. 2. Extraction using polar solvent
Powdered drug is extracted with aqueous or alcoholic
dilute acid solution, filtered and concentrated on water
bath till complete evaporation of alcohol.
The concentrated extract is shaken with organic solvent
like chloroform or ether to remove pigments and other
unwanted materials.
31

32. The strong ammonia solution is then added to
concentrated extract containing alkaloidal salts to
precipitate alkaloidal bases.
Alkaline extract is extracted with chloroform or ether
and evaporated to dryness.
The dried residue is weighed, which gives total alkaloidal
content of drug.
32

33. The further purification of crude extract of alkaloids is done
by following ways:
1. Direct crystallization from solvents
It is very simple method of isolation and may not be
useful in case of complex mixture.
2. Chromatographic Techniques
The method has proved to be ideal for separation of a
vast number of plant alkaloids.
33

34. The different techniques of chromatography TLC, HPTLC,
HPLC, Gas chromatography and Ion exchange
chromatography are used for separation of individual
alkaloids from complex mixtures.
3. Gradient pH technique
Alkaloids are basic in nature, there are variations in the
extent of basicity of various alkaloids of the same plants.
34

35. Crude alkaloidal mixture is dissolved in 2% tartaric acid
solution and extracted with benzene so that the first fraction
contains neutral and/or very weakly basic alkaloids
pH of the aqueous solution is increased gradually by 0.5
increments upto 9 and extraction is carried out at each pH
level with organic solvent
Alkaloids with different basicity are extracted and separated
Strongly basic alkaloids are extracted at the end (increasing
order of basicity)
35

36. 36
Phytochemical Screening

37. Tests Experiments Observations
Dragendorff´sDrug solution + solution of
potassium bismuth iodide
Brownish red
color
Mayer´s Drug solution + solution of
potassium mercuric iodide
Creamy white
ppt
Hager´s Drug solution + solution of
picric acid
Crystalline
yellow ppt
Wagner´s Drug solution + solution of
iodine & potassium iodide
Reddish brown
ppt
Tannic acidDrug solution + few drops
tannic acid solution
Buff color ppt
Valser´s testDrug solution + Mercuric
iodide
White ppt
37

38. Classification of Alkaloids
1. Pharmacological Classification
 CNS stimulant
 CNS depressant
 Sympathomimetics
 Analgesic
 Purgative
38

39. 2. Taxonomical Classification
The method classifies the vast number of alkaloids based
on their distribution in various plant families, like
Solanaceous or Papillionaceous alkaloids.
Preferably they are grouped as per the name of the genus
in which they occur, like Ephedra, Cinchona etc.
From this classification, the chemotaxonomic
classification further derived.
39

40. 3. Biosynthetic Classification
The 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 same precursor like all
indole alkaloids synthesized from tryptophan are grouped
together.
The alkaloidal drugs are categorized on the fact whether they
are derived from amino acid precursor as ornithine, lysine,
tyrosine, phenylalanine, tryptophan etc.

40

41. 4. Chemical classification
This method is most accepted way of classification of
alkaloids.
The main criterion for chemical classification is the type of
fundamental (heterocyclic) ring structure present in alkaloid.
Alkaloids are broadly categorized into two divisions:
A.Heterocyclic alkaloids (True alkaloids) are divided into twelve
groups according to nature of their heterocyclic ring.
B. Non-heterocyclic alkaloids or proto-alkaloids or biological
amines or pseudoalkaloids.
41

42. Pyridine-Piperidine Combined
Tropane
Quinoline
Isoquinoline
Indole
Imidazole
Steroid
Alkaloidal amine
Purine

43. 43
Piperidine
Purine Steroid nucleus

44. 44
PyrrolizidineNorlupinaneDiterpene
Tropane Imidazole

45. Common Amino Acid Precursors:
Phenylalanine
Tyrosine
Tryptophan
Histidine
Anthranilic acid
Lysine
Ornithine

46. Ornithine/Tropane/Solanaceous alkaloids:
46

47. Belladonna Leaf:
Synonyms: Deadly night shade leaf
Biological source: Dried leaf and flowering top of Atropa belladonna
(Solanaceae)
Chemical profile: Tropane alkaloids (0.3-0.6%); l-Hyoscyamine
(atropine) is prominent one. Others are apoatropine, choline,
scopoletin.
Uses: Anticholinergic, narcotic, sedative, mydriatic, anodyne
Marketed Products
It is one of the ingredients of the preparation known as Belladona
plaster (Surgi Pharma) for backache, stiffness of muscles and boil,
swollen joints.
47

48. Hyoscyamine Hyoscine
48Tropane

49. Hyoscyamus:
Synonyms: Hog bean, Insane root, Henbane
Biological source: Dried leaf and flowering top of
Hyoscyamus niger (Indian), H. muticus (Egyptian)
(Solanaceae)
Uses: Smooth muscle relaxant, Mydriatic, Parasympatholytic
49

50. Stramonium:
Synonyms: Thorn apple
Biological source: Dried leaf and flowering top of Datura
stramonium, D. metel (Indian), (Solanaceae).
50

51. 51

52. 52

53. 53

54. 54
Tyrosine/Dihydroxyphenyl alanine/
alkaloidal amines:

55. 55

CH
2CH COOH
NH
2
Phenylalanine
CH
2CH COOH
NH
2
OH
Tyrosine
CH
2CH COOH
NH
2
OH
OH


Amines Benzylisoquinoline Bisbenzylisoquinoline MVA Participation Phenylethylisoquinoline
Derivatives Group (d-tubocurarine) Alkaloids



Ephedrine Papaverine Emetine Colchicine
Mescaline Morphine





Dihydroxyphenylalanine (Dopamine)

56. Opium:
Synonyms: Opium
Biological source: Latex from unripe capsule of Papaver
somniferum (Papaveraceae)
Chemical profile:
Morphine (10-16%)
Alkaloids are combined with meconic acid
Codeine (0.8-2.5%), narcotine, thebaine (0.5-2%),
noscapine (4-8%), narceine, papaverine (0.5-2.5%)

57. Morphine contains Phenanthrene nucleus
The different alkaloids are
1)Morphine type: Morphine, codeine, neopine, pseudo or
oxy-morphine, thebaine, porphyroxine
2)Pthalide isoquinoline: Noscapine, narcotine, narceine,
narcotoline, hydrocotarnine
3)Benzyl isoquinoline: Papaverine, codamine, xanthaline,
laudanine, laudanosine
4) Cryptopine type: Protopine, cryptopine
5) Unknown: Aporeine, meconidine, papaveramine,
lanthopine, rhodeadine
57

58. Chemical test:
Aqueous extract gives reddish purple color with FeCl
3
which persists on addition of HCl
Morphine gives dark violet color with Conc. H
2
SO
4
and
HCHO
58

59. Uses:
Morphine is narcotic analgesic, sedative
Codeine in mild sedative and used in cough formulations
Noscapine is non-narcotic and cough suppressant, hence
used as central antitussive
Papaverine is smooth muscle relaxant, cure muscle spasm
Diacetyl morphine (heroin) cause drug addiction
Opium is astringent, myotic, check hemorrhages, in
diarrhoea, dysentery, somniferous
59

60. Noscapine
60

61. 61
Laudanosine

62. 62

63. Tryptophan derived/Indole alkaloids:
63

64. 64

65. 65

66. 66

67. Rauwolfia:
Synonyms: Sarpagandha, Indian snake root
Biological source: Rauwolfia serpentina roots (Apocynaceae)
Chemical profile:
Total alkaloids (0.7-2.4%)
Reserpine, rescinnamine, deserpidine, ajmaline
(rauwolfine), ajmalicine (Yohimbine), alstonine, rescidine
67

68. Uses:
Antihypertensive, sedative & hypnotic, increase uterine
contraction so used in labor, neuropsychiatric disorders
Marketed Products
It is one of the ingredients of the preparations known as
Confido, Lukol, Serpina (Himalaya Drug Company) and
Sarpagandhan bati (Baidyanath).
68

69. 69
Reserpine
Deserpidine
Ajmaline

70. Ajmalicine Rescinnamine
Alstonine
70

71. Synonyms: Shadabahar, Rattanjot, Periwinkle
Biological source: Whole plant of Catharanthus roseus or Vinca rosea
(Apocynaceae)
Chemical profile:
Catharanthine, vindoline are monomeric alkaloids
Vinblastine, vincristine, vindesine are dimeric
Ajmalicine, reserpine, serpentine, lochnerine
Uses:
Diabetes, wasp sting
Vinblastine sulphate is antitumor used in Hodgkin's disease
Vincristine sulphate is cytotoxic used to treat leukemia in children
Catharanthus:

72. 72
Marketed Products
It is one of the ingredients of the preparation known as
Cytocristin (Cipla).

73. Catharanthine 73

74. 74