1. Tahir Ali Lecturer RIPS, RIU
Alkaloids
Tahir Ali
Lecturer
RIPS, RIU

2. Please VOMIT answer of some kind
Any Guess
Please VOMIT answer of some kind

3. Definition
Alkaloids are extremely difficult to define because of two major reasons:
Their diverse heterogeneous nature
There is no clear-cut boundary between alkaloids and naturally occurring complex amines.
However, typical alkaloids could be define as:
Alkaloids
However, typical alkaloids could be define as:
“They are mostly derived from plant sources, they are basic in nature, they contain one or more nitrogen atoms (usually in a heterocyclic ring) and they usually have a marked physiological action on man or other animals.”

4. Nicotine
caffeine

5. mn
Conti…
Alkaloid
Alk = Alkali
Oid= Like
Vegetable Alkali

6. Alkaloids are found as secondary metabolites in plants (e. g
Alkaloids are found as secondary metabolites in plants (e.g. in Vinca and Datura), animals (e.g. in shellfish) and fungi.
They can be extracted from their sources by treatment with acids (usually hydrochloric acid or sulphuric acid, though organic acids, such as maleic acid and citric acid are sometimes used).
Alkaloids are found as secondary metabolites in plants (e.g. in Vinca and Datura), animals (e.g. in shellfish) and fungi, and can be extracted from their sources by treatment with acids (usually hydrochloric acid or sulphuric acid, though organic acids, such as maleic acid and citric acid are sometimes used).
Alkaloids

7. Physico-chemical properties
In general, they are colourless, crystalline solids which are basic, have a ring structure, and have definite melting points, bitter taste.
In the plant they may exist in the free state, as salts or as N-oxides.
Elements carbon, hydrogen and nitrogen, most alkaloids contain oxygen.
A few, such as coniine from hemlock and nicotine from tobacco, are oxygen-free and are liquids.

8. Cont.
Although colored alkaloids are relatively rare, berberine, for example, is yellow and the salts of sanguinarine are copper-red.
Generally free bases of alkaloids are soluble in organic solvents and insoluble in water, where as alkaloidal salts are soluble in water and partially soluble in organic solvents.
For example, strychnine hydrochloride is much more soluble in water than strychnine as a base.

9. CLASSIFICATION There are three main types of alkaloids:
(1) True alkaloids,
(2) Protoalkaloids
(3) Pseudoalkaloids
1) True Alkaloides
2) Protoalkaloides
3) Pseudoalkaloides

10. True Alkaloids
True alkaloids derive from amino acid and they share a heterocyclic ring with nitrogen. These alkaloids are highly reactive substances with biological activity even in low doses.
All true alkaloids have a bitter taste and appear as a white solid, with the exception of nicotine which has a brown liquid. True alkaloids form water-soluble salts.
True alkaloids may occur in plants;
(1) in the free state, (2) as salts and (3) as N-oxides.

11. Cont.…
The primary precursors of true alkaloids are such amino acids as:
L-ornithine,
L-lysine,
L-phenylalanine/Ltyrosine,
L-tryptophan and L-histidine.
Examples of true alkaloids include such biologically active alkaloids as cocaine, quinine and morphine.

12. Morphine
Atropine

13. Protoalkaloids:
Protoalkaloids are compounds, in which the N atom derived from an amino acid is not a part of the heterocyclic.
Such kinds of alkaloid include compounds derived from L-tyrosine and L-tryptophan.
Protoalkaloids are those with a closed ring, being perfect but structurally simple alkaloids. They form a minority of all alkaloids.
Hordenine, mescaline and yohimbine

14. Mescaline

15. Pseudoalkaloids Not derived from amino acids
They are derived from the precursors or post-cursors of amino acids.
Can also be derived from non aminoacid precursors e.g. steroidal or terpenoid
Coniine, capsaicin, ephedrine, solanidine, caffeine and theobromine

16. Nicotine
caffeine

17. Nomenclature
The name of all alkaloids should end with the suffix ‘-ine’.
The names of the alkaloids are obtained in various ways:
From the generic name of the plant yielding them, e.g. atropine.
From the specific name of the plant yielding them, e.g. cocaine.
From the common name of the drug yielding them, e.g. ergotamine.
From their physiologic activity, e.g. emetine.
From the discoverer, e.g. pelletierine.

18. CHEMICAL TESTS Dragendorff’s Test Mayer’s Test Hager’s Test
Drug solution + Dragendroff ’s reagent (Potassium Bismuth Iodide), formation of Orange red colour.
Mayer’s Test
Drug solution + few drops of Mayer’s reagent (potassium mercuric iodide), formation of creamy-white precipitant.
Hager’s Test
Drug solution + few drops of Hagers reagent (Saturated aq. Solution of Picric acid), formation of crystalline yellow precipitate.
Wagner’s Test
Drug solution + few drops of Wagner’s reagent (dilute Iodine solution), formulation of reddish-brown precipitate.

19. Functions of alkaloids in plants
There are several speculations about the advantages of their presence in plants, including:
Poisonous agents protecting the plant against insects and herbivores “Animals that feed chiefly on plants”.
End products of detoxification reactions.
Regulatory growth factors.
Reserve substances capable of supplying nitrogen or other elements necessary to the plant’s economy.

20. Extraction of alkaloids
Method A and Method B
Extraction of alkaloids
The conventional process involved in the alkaloids separation and isolation may be divided as follows:
Preparation of the sample.
Liberation of the free alkaloidal base, by treating the dried material with suitable alkali.
Extraction of the alkaloidal base with an organic solvent.
Purification of the alkaloidal extract.

22. Classification on the bases of ring structure of chief Alkaloid group
Pyridine-Piperidine
Tropane
Quinoline
Isoquinoline
Indole
Imidazole
Steroid
Alkaloidal amines
Purine

23. 1- Pyridine-Piperidine Alkaloids

24. Pyridine- Piperidine Combined
Also referred to as Pyrrolizidine alkaloids
Upon reduction, the tertiary base, pyridine, is converted into the secondary base, piperidine.

25. Important alkaloidal drugs and alkaloids that are classified in this group are:
Tobacco
Nicotine
Areca
Arecoline
Lobelia
Lobeline

26. TOBACCO Biological Source : Nicotiana tobaccum Family : Solanaceae
History:
Nicotiana – was named after Jean Nicot who introduced tobacco in Europe.
Tabacum – refers to the Indian name for the pipe or tube used in smoking it.

27. Chemical Constituents
The most important constituent is the alkaloids nicotine and nicotinine.
It is colorless to pale yellow, very hygroscopic, oily, volatile liquid with unpleasant, pungent odor and a sharp, burning, persistent taste.

28. After leaves are smoked the nicotine decomposes into
Pyridine,
Furfurol,
Collidine,
Hydrocyanic acid,
Carbon monoxide, etc.
The poisonous effects of Tobacco smoke are due to these substances of decomposed nicotine.

29. USES:
It is bound to an ion exchange resin in a chewing gum base as a temporary aid to the cigarette smoker seeking to give up smoking.
Chronic use of nicotine may result in psychological and physical dependence.

30. Areca Areca nut or Betel Nut A dried, ripe seed of Areca catechu
Family Palmaceae.
Areca- a Spanish and Portuguese term for betel nut

33. Catechu- East Indian name for an astringent extract or juice
Constituents ;
Alkaloids …….. such as;
Arecoline
Arecaine
Guvacine
Arecoline is present in about 0.1–0.5% yield and is medicinally important.
Fat (14%)
Red tannin (15%)

34. Uses: Anthelmintic or vermicide in veterinary practice
Chewing of Areca nut may cause mouth cancer

35. LOBELIA Indian tobacco
Consists of dried leaves and tops of Lobelia inflata Linné (Fam. Lobeliaceae)
Lobelia – named in honour of a Flemish botanist Matthias de L’ Obel

36. Lobeline Constituents volatile oil Resin Lipids gum Lobeline
Inflata – refers to a hollow and distended fruit
Substitute for tobacco
Constituents
Lobeline
volatile oil
Resin
Lipids
gum
Lobeline

37. Uses
Similar but weaker pharmacological effects in nicotine on the peripheral circulation, neuromuscular junctions, and CNS.
Anti-smoking preparations;
Lobeline had placebo effect on decreasing the physical craving for cigarettes
Traditionally used by the Native Americans for asthma and chronic bronchitis

38. Reference book: Pharmacognosy , Verro E. Tyler, (9th edition)
Textbook of Pharmacognosy and Phytochemistry, Biren N. Shah and A.K. Seth, (First Edition 2010).
Pharmacognosy , Verro E. Tyler, (9th edition)

39. Part 4

40. ISOQUINOLINE ALKALOIDS
Isoquinoline is a double carbon ring containing one nitrogen atom.

41. ISOQUINOLINE ALKALOIDS
contain the isoquinoline ring structure
Sources:
Alkaloid(s)
Ipecac
Emetine
Hydrastis
Berberine, Hydrastine
Sanguinaria
Sanguinarine
Curare
Tubocurarine
Opium
Morphine, Codeine, Thebaine

42. IPECAC B.O. Cephaelis ipecacuanha Family: Rubiaceae
Part Used: rhizomes and roots of
Constituents: Ipecac root contains 2–3% of total alkaloids:
1. Emetine
2. Cephaeline
3. Psychotrine

43. Emetine
Cephaeline

44. Chemical Test of Emetine
Powdered drug (0.5 g) is mixed with HCl (20 ml) and water (5 ml), filtered and to the filtrate (2 ml) potassium chloride (0.01) is added. If emetine is present, a yellow colour develops which on standing for 1 hour gradually changes to red.

45. Uses
Ipecac is emetic and used as an expectorant and diaphoretic and in the treatment of amoebic dysentery.
Syrup of ipecac is used to empty the stomach after poisoning or drug overdose.
Emetine has a more expectorant and less emetic action than cephaeline.
Psychotrine and its methyl ether are selective inhibitors of human immunodeficiency virus.

46. HYDRASTIS (Goldenseal)
B.O Hydrastis Canadensis
Family: Ranunculaceae
Part Used: dried rhizome and roots
Constituents: 3 principal alkaloids
1. Hydrastine
2. Berberine (astringent in inflammation
of mucous membranes)
3. Canadine

47. Berberine

48. SANGUINARIA (Bloodroot)
B.O Sanguinaria Canadensis
Part Used: Rhizome of
Family: Papaveraceae

49. Alkaloids (Protopine series):
Sanguinarine
Chelerythrine
Protopine
Allocryptopine
Uses:
Stimulating expectorant
Emetic
Sanguinarine

50. Let’s Draw the Structure

51. bb
Emetine
Cephaeline

52. Berberine

53. Sanguinarine

54. Thanks

55. OPIUM Alkaloids: gum opium
milky exudate (air-dried) obtained by incising the riped capsule of Papaver somniferum
opium poppy – plant source
Alkaloids:
1. morphine – 4-12%
2. codeine – 0.8 – 2.5%
3. noscapine (formerly narcotine) – 4- 8%
4. papaverine – 0.5 – 2.5%
5. thebaine – %
6. meconic acid – 3-5%

56. checks excessive peristalsis miotic
Uses:
Stimulant-depressant (first stimulates and then depresses nerve response)
analgesic
narcotic
checks excessive peristalsis
miotic
Powdered opium
used in making Dover’s powder and camphorated opium tincture
combined with antidiarrheal preparations
Paregoric or camphorated opium tincture
antiperistaltic
Laudanum, opium tincture, deodorized opium tincture
Maw or poppy seed
bluish black or yellowish white
contains no significant quantity of alkaloids

57. Morphine DIDEHYDROXYEPOXY METHYLMORPHINANDIOL
most important of the opium alkaloids
narcotic analgesic
strongly hypnotic and narcotic
induces vomiting, constipation and habit formation
structural features CNS acting analgesic:
quaternary- central carbon atom with no H substitution
a phenyl group or isostere attached to central C atom
tertiary nitrogen atom
2 – carbon bridge separating (3) and (1)

58. Codeine most widely used opium alkaloid
a methylmorphine in which the methyl group replaces the hydrogen of the phenolic hydroxyl group
occurs as fine needles or white crystalline powder
Uses:
Narcotic analgesic
Antitussive
Sedatives in allaying coughs
Less toxic and involves lesser danger of habit formation compared to codeine

59. Diacetylmorphine or heroin
formed by acetylation of morphine
action is similar, yet more pronounced than that of morphine
Apomorphine HCl
morphine treated with HCl
one water molecule is lost
emetic; used subcutaneously in cases of poisoning

60. Paparavine HCl Hydromorphone HCl or dihydroxymorphine HCl
muscle relaxant
antitussive in combination with codeine sulfate
Hydromorphone HCl or dihydroxymorphine HCl
one of the hydroxyl groups of morphine is replaced by a ketone group; adjacent double bond is removed
prepared by reducing morphine in HCl solution with H in the presence of a catalyst
powerful narcotic analgesic
strongly depresses reeperatory mechanism
Hydrocodone bitartrate or dihydrocodeine bitartrate
antitussive

61. Noscapine Opioid synthetic morphinelike compounds nonhabit forming
commonly called narcotine
exists as free base in opium
no narcotic properties (anarcotine)
antitussive
Opioid
synthetic morphinelike compounds
nonhabit forming
others are antitussive

62. Part 5

63. CURARE Alkaloids: Tubocurarine
From bark and stem of Strychnos castelnaei
Belonging to family Loganiaceae
Alkaloids:
Tubocurarine

64. Curare effect
paralyzing effect on voluntary muscle exhibit by the crude extract
Uses:
skeletal muscle relaxant
control convulsions of strychnine poisoning and of tetanus
diagnostic aid in myasthenia gravis

65. INDOLE ALKALOIDS
Indole (1-H-indole) is a benzopyrrole in which the benzene and pyrrole rings are through the 2, 3-positions of the pyrrole.

66. INDOLE ALKALOIDS 4. Physostigma 5. Ergot 1.Rauwolfia 3. Nux vomica
-reserpine
-rescinamine
-deserpidine
2. Catharanthus (vinca)
-vinblastine
-vincristine
3. Nux vomica
-strychnine
-brucine
4. Physostigma
-physostigmine
5. Ergot
-ergotamine
-ergonovine

67. RAUWOLFIA SERPENTINA Chemical Constituents Indian snake root.
belonging to family Apocynaceae.
Dried roots of Rauwolfia serpentina
Chemical Constituents
0.7–2.4% total alkaloidal bases
80 alkaloids have been isolated.
The prominent alkaloids are:
Reserpine,
Rescinnamine,
Rescidine,
Deserpidine
Ajmalinine,
serpentine

69. USES:
Hypotensive
Hypnotic,
Sedative
Ajmaline  Cardiac arrhythmias

70. CATHARANTHUS Vinca and periwinkle
Dried whole plant of catharanthus roseus
Belonging to family Apocynaceae
Have anticancer potential

71. Constituents About 90 alkaloids have been isolated
The important alkaloids are Vinblastine and Vincristine

72. Uses:
Vinblastin is an antitumour alkaloid used in the treatment of Hodgkin’s disease.
Vincristine is used to treat leukaemia in children.
In cases of scurvy, sore throat and inflamed tonsils, it may also be used as a gargle.
It is also used in the treatment of diabetes.
The flowers are gently purgative, but lose their effect on drying. If gathered in the spring and made into a syrup, then, it could be used as gentle laxative for children and also for overcoming chronic constipation in grown persons

73. NUX VOMICA ALKALOIDS; Brucine Dried ripe seed of Strychnos nux vomica
Family Loganiaceae
ALKALOIDS;
Strychnine
Brucine

76. Uses:
Digestive problems such as constipation, bloating, heartburn, and nausea
Often combined with cascara and other laxatives with good effects
Male infertility and impotence

77. ERGOT Ergot is the dried sclerotium of a fungus, Claviceps purpurea
Belonging to family Clavicipitaceae
Developing in the ovary of rye plant, Secale cereale (Family Poaceae).

78. Cultivation and Collection
The life cycle of the fungus, Claviceps purpurea, which is a parasite, passes through the following characteristic stages:
1. Sphacelia or honeydew or asexual stage
2. Sclerotium or ascigerous or sexual stage
3. Ascospore stag.

81. Uses
Ergot is oxytocic, vasoconstrictor and abortifacient and used to assist delivery and to reduce post-partum haemorrhage.
Lysergic acid diethylamide (LSD-25), obtained by partial synthesis from lysergic acid, is a potent specific psychotomimetic.

82. Reference book: Pharmacognosy , Verro E. Tyler, (9th edition)
Textbook of Pharmacognosy and Phytochemistry, Biren N. Shah and A.K. Seth, (First Edition 2010).
Pharmacognosy , Verro E. Tyler, (9th edition)

83. Thanks