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ALKALOIDAL AMINES
DR. HARISHKUMAR N. KAKRANI,PRICIPAL,
C. V. M INSTITUTE OF DEGREE COURSE IN PHARMACY (institute code: 272), VALLABH VIDYANAGAR 388 121
Subject name: PHARMACOGNOSY-4Subject code: 250006
2
ALKALOIDS
• Alkaloids are a group of naturally occurring organic substances, having nitrogen in their heterocyclic ring.
o Except few i.e. proto- and pseudo-alkaloids that do not have nitrogen in their structural rings.
• Most alkaloids contain oxygen; those compounds are usually colorless crystals at ambient conditions.
o Oxygen-free alkaloids, such as nicotine or coniine are typically volatile, colorless, oily liquids.
o Some alkaloids are colored, like berberine (yellow) and sanguinarine (orange).
• Most alkaloid are weak bases, but some are amphoteric, for example theobromine and theophylline.
• Most alkaloids are poorly soluble in water but readily dissolve in organic solvents, such as diethyl
ether, chloroform and 1,2-dichloroethane.
o However, caffiene dissolves well in boiling water.
• With acids, alkaloids form salts of various strengths.
o Those salts are usually soluble in water and alcohol and poorly soluble in most organic solvents.
o Exceptions include scopolamine hydrobromide which is soluble in organic solvents and water-
soluble quinine sulfate.
• Alkaloids occur as free bases, salts or N-oxides (N→O). When the salt of an alkaloid is treated with
hydroxyl ion, nitrogen gives up a hydrogen ion and the free amine is liberated.
Alkaloidal amines, Dr. Harish Kakrani, CDCP
3
• May be of plant or animal origin
• Nitrogen of alkaloids: The Nitrogen atom can either be 1˚, 2˚, 3˚ or 4˚ (quaternary).
• Alkaloids are usually bitter in taste.
• They are optically active.
o Generally the levo rotatory isomer l (-) is pharmacologically more active than the dextro rotatory
isomer d (+) of the same alkaloid.
o Exception: d(+) pilocarpine, d(+) tubocurarine and d(+) quinidine are medically used.
• Alkaloids are pharmacologically active even in microgram quantities.
– Plant alkaloids usually have profound physiological actions in humans even in microgramme
quantity with nervous system effects being the most prominent.
– Examples of some of the more dramatic actions of alkaloids are:
Analgesics/ narcotics—morphine Mydriatics—atropine Miotics—pilocarpine
Hypertensives—ephedrine Hypotensives—reserpine Bronchodilator—lobeline
Stimulants—strychnine Antimicrobials—berberine Antileukemic—vinblastine
• BIOGENESIS OF ALKALOIDS:
o Alkaloids are produced in plants by basic substances and reactions well-known in organic
chemistry.Alkaloidal amines, Dr. Harish Kakrani, CDCP
ALKALOIDS
Alkaloidal amines, Dr. Harish Kakrani, CDCP 4
BIOGENESIS OFALKALOIDS
• True alkaloids are based on an amino acid (pre-cursor). Only a few amino acids form the pre-
cursors for all alkaloids: ornithine, lysine, phylalanine, tyrosine, tryptophan, histidine and
anthranilic acid.
Alkaloidal amines, Dr. Harish Kakrani, CDCP 5
OCCURRENCE & DISTRIBUTION OF ALKALOIDS
• Occur in bacteria (Pseudomonas aeruginosa) and rarely in fungi (pscilocin from hallucinogenic
mushrooms).
• Some alkaloids occur in several genera from different species (caffeine), but most occur in
closely related species.
• Some occur in certain families (hyoscyamine), while others occur only in a specific species
(morphine).
• Rarely do plants contain more than 1 type of alkaloid.
• All alkaloids of one plant will have a common biogenetic origin
• Alkaloids occur in all plant parts, but are usually localized in one organ (e.g. the bark or seeds).
• Within the plant, alkaloid can vary widely from part to part – some parts may contain no alkaloids.
• Occasionally, different alkaloids also form in different parts of the plant.
Alkaloidal amines, Dr. Harish Kakrani, CDCP 6
ALKALOIDS
True Alkaloids
Nitrogen in its heterocyclic ring system
Derived from amino acids
Proto-alkaloids (AMINO- ALKALOIDS)
Have no nitrogen as a part of their heterocyclic
ring
Derived from amino acids
Pseudo-alkaloids
These alkaloids have heterocyclic ring with
nitrogen in it
But these are not derived from amino
acids
CLASSIFICATION OF ALKALOIDS
Alkaloidal amines, Dr. Harish Kakrani, CDCP 7
CLASSIFICATION OF TRUE ALKALOIDS
Sr. No. Class Examples Species Pharmacological actions
1Pyridine/piperidine
Nicotine Nicotiana tabacum Adrenergic, CNS stimulant
Lobeline Lobelia inflata Expectorant, bronchodilator
Piperine •Piper nigrum•P. longum
•Stimulant•hepatoprotective
Arecoline Areca catechu Vermicide, taenifuge
2 Tropane
Hyoscyamine Atropa belladonna Anticholinergic, Antisialagogue
Cocaine Erythroxylon coca CNS stimulant, anaesthetic, narcotic
Scopalamine Datura metel Anticholinergic, CNS depressant
3 Quinoline Quinine Cinchona spp. Antimalarial, Antiarrhythmia
Quinidine - Cardioactive
4 Isoqinoline
Berberine Berberis spp. Antimicrobial, antiprotozoal,cholagogue
Morphine Papaver somniferum Sedative, analgesic, Narcotic
Chelidonine Chelidonium majus Spasmolytic, cholagogue
Boldine Pneumus boldo Spasmolytic, choleretic
Emetine Cephaelis Ipecacuanha Emetic
Alkaloidal amines, Dr. Harish Kakrani, CDCP 8
Sr. No.
Class Examples Species Pharmacological actions
5 Quinolizidine Sparteine Sarothamnus
scopariusOxytocic, cardiotonic, diuretic
6 Pyrrolizidine •Sececionine•Symphytine
•Senecio jacobeae •Symphytum spp.
Hepatotoxin
7 Indole
Reserpine Rauwolfia serpentina Sedative, Antihypertensive
Ergotamine Claviceps purpurea Vasoconstrictor, hypertensive
Strychnine Strychnos nuxvomica CNS stimulant, deadly toxin
Yohimbine Aspidosperma quebracho Aphrodisiac, stimulant
8 Imidazole Pilocarpine Pilocarpus jaborandi Miotic, cholinergic
CLASSIFICATION OF TRUE ALKALOIDS
CLASSIFICATION OF PROTOALKALOIDS
Sr. No. Class Examples Species Pharmacological actions
1
Alkaloidal amines (proto-
alkaloids)
Colchicine Colchicum autumnale Antimitotic, uric acid amines solvent
Ephedrine Ephedra sinica Sympathetic stimulant,bronchodilator
Mescaline Lophophora williamsii Hallucinogenic
Alkaloidal amines, Dr. Harish Kakrani, CDCP 9
Sr. No. Class Examples Species Pharmacological actions
1Purine
alkaloids
Caffeine Coffea arabica CNS and sympathetic stimulant
Theophylline Thea sinensis Bronchodilator, diuretic
Guaranine Paullinia cupana CNS and sympathetic stimulant
2Steroidal alkaloids
Solanine Solanum spp. Steroid precursors, anti-inflammatory
Veratrine Veratrum album Cardiac depressants,antihypertensives
3Terpenoidal alakaloids
Aconitine Aconitum spp. Antipyretic, analgesic, neurotoxin
CLASSIFICATION OF PSEUDO-ALKALOIDS
Alkaloidal amines, Dr. Harish Kakrani, CDCP 10
AMINO-ALKALOIDS
(PROTO-ALKALOIDS)
Alkaloidal amines, Dr. Harish Kakrani, CDCP 11
AMINO ALKALOIDS
GENERAL CHARACTERISTIC FEATURES:
• Protoalkaloids
• Have no nitrogen as the part of the heterocyclic ring.
• Derived from amino acid like l- phenyl alanine.
• Physiologically active compounds
• Example: Ephedrine (Ephedra species) and Colchicine (Colchicum autmnale)
BIOSYNTHESIS OF AMINO ALKALOIDS:
• Amino alkaloids are derived from amino acid l- phenyl alanine through shikkimic acid pathway.
• The pathway finds its route from carbohydrates for the biosynthesis of C6- C3 units (i.e. phenyl
propane derivatives) like phenyl alanine and tyrosine
• An important branching point arises at chorismic acid, which acts as a precursor for different amino
acids.
Alkaloidal amines, Dr. Harish Kakrani, CDCP 12
BIOSYNTHESIS OF AMINO ALKALOIDS
Dehydration
3- dehydroShikimic acid
SHIKIMIC ACID
Alkaloidal amines, Dr. Harish Kakrani, CDCP 13
Shikimicacid
Dehydration
Shikimic acid-3- phosphate
Phosphoenol pyruvic acid
5- enolpyruvyl shikimate-3- phosphate
CHORISMIC ACID
Prephenicacid
Phenyl pyruvic acid
PHENYL ALANINE
BIOSYNTHESIS OF AMINO ALKALOIDS
Alkaloidal amines, Dr. Harish Kakrani, CDCP 14
BIOSYNTHESIS OF AMINO ALKALOIDS
Phenyl alanine
Ephedrine (Ephedrine spp.)
Colchicine(Colchicum autumnale)
Alkaloidal amines, Dr. Harish Kakrani, CDCP 15
GENERAL PHARMACOLOGICAL ACTION & USES OF AMINO- ALKALOIDS
• Cause
– Dilation of the bronchi (asthma),
– Increase heart rate and
– Peripheral vasoconstriction
Alkaloidal amines, Dr. Harish Kakrani, CDCP 16
EPHEDRA
Alkaloidal amines, Dr. Harish Kakrani, CDCP 17
EPHEDRA
• Synonym: Ma-Huang.
• Biological source: It consists of dried young stems of Ephedra gerardiana (wall.) Stapf, and E. nebrodensis
(Tineo) Stapf.
o Family: Gnetaceae (Ephedraceae).
o Ephedra should contain not less than 1% of total alkaloids, calculated as ephedrine.
• Geographical source: China, Pakistan, North-west parts of India, Australia, Kenya, Spain & Yugoslavia.
• Cultivation, Collection & preparation:
o Cultivated at an altitude of 2500- 3000 m.
o Annual rainfall should not exceed 50cm.
o Propagated by seeds or by layers or divisions of root stock.
o Seeds sown early in spring at a distance of 5cm, keeping distance of 1 mt between 2 rows
o Collected after attaining the age of 4 yrs for extraction of alkaloid
o Alkaloid content varies from season to season.
It is maximum in autumn
o Twigs dried in sun or even by artificial ways.
o Stored in dry & well closed containers
Alkaloidal amines, Dr. Harish Kakrani, CDCP 18
• Macroscopic Characters:
o General appearance: Thin cylindrical or ellipsoidal cylinder,
o Size: 1–2 mm in diameter; 3.5–5.5cm in length of internode;
o Color: Light green to yellow-green;
o Surface: numerous parallel vertical furrows on the surface; scaly leaves at the node
portion;
o Leaves: 2–4 mm in length, light brown to brown in colour, usually opposite at every
node, adhering at the base to form a tubular sheath around the stem.
o Transverse section of the stem: appears as circle and ellipse, the outer portion
greyish green to yellow-green in colour, and the centre filled with a red-purple
substance or hollow.
o Fracture at an internode: the outer part is fibrous and easily split vertically
o Odour: slight;
o Taste: slightly bitter and astringent, giving a slight sensation of numbness on the
tongue .
EPHEDRA
Alkaloidal amines, Dr. Harish Kakrani, CDCP 19
Macroscopical characteristics of
Ephedra Stem &
Leaves
EPHEDRA
Alkaloidal amines, Dr. Harish Kakrani, CDCP 20
• Microscopic characteristics:
1. STEM:
• The epidermal cells of the stem covered with a moderately thick granular cuticle; the cells are
polygonal or subrectangular, axially elongated, having straight anticlinal walls.
• The stomata are few and are of the ranunculaceous type with lignified appendages.
• Cortical parenchyma and pith cells contain an amorphous reddish brown substance.
• Non-lignified or lignified hypodermal and pericyclic fibres, which have thick walls, bear slit-like pits
and blunt, slightly tapering, occasionally forked ends.
• The vessels of the secondary xylem of the stem are lignified with bordered pits, having rounded or
oval apertures.
• Few, small, rounded, simple and compound starch granules with indistinct hilum are present in
cortical parenchyma, pith, and medullary ray cells.
• Few, small prisms of calcium oxalate are present in the cortical parenchyma.
2. LEAF:
• The epidermis of the scaly leaf is covered with smooth (upper) or warty (lower) cuticle and consists
of subrectangular to polygonal cells, having straight or sometimes slightly beaded anticlinal walls;
few stomata are present resembling those of stem.
EPHEDRA
Alkaloidal amines, Dr. Harish Kakrani, CDCP 21
• The epidermis of the apical and marginal regions of the scaly leaf shows short papillae-like
outgrowths.
• Chlorenchymatous palisade-like cells form the outer zone of the cortex; rounded ordinary
parenchymatous cells form the inner zone of the cortex.
• The fibres of the scaly leaf are lignified.
• Powder characteristics:
o Powdered herb is greyish green.
o The characteristics observed are as follows:
• Thick fragments of cutinized outer walls of epidermis
• Sclerenchyma fibres with extremely thickened, non-lignified to lignified walls, narrow, frequently
indistinct lamina and sharp pointed ends.
• Fragments of vascular tissue showing spiral and pitted tracheae.
• Fragments of epidermis with sunken elliptical stomata
EPHEDRA
Alkaloidal amines, Dr. Harish Kakrani, CDCP 22
EPHEDRA
Powder characteristics of Ephedra stemTransverse Section of Ephedra Stem
Alkaloidal amines, Dr. Harish Kakrani, CDCP 23
• Chemical constituents:
o Amino alkaloids: Ephedrine, nor-ephedrine, n-methyl ephedrine, pseudo-ephedrine.
o Chemically, ephedrine is 1-phenyl-1- hydroxy-2- methylaminopropane
• Soluble in water, alcohol, organic solvents and oil
• Odourless & colourless
• Deliquescent
• Decomposes when exposed to air.
o Other constitutents:
• Macrocyclic alkaloids- ephedradines present in roots.
• Oxazolidone.
EPHEDRA
Ephedrine Nor-ephedrine
N-methyl ephedrine
Alkaloidal amines, Dr. Harish Kakrani, CDCP 24
• Chemical Tests:
o Ephedrine dissolved in water & dil. HCl treat individually with Copper sulfate & NaOH
Violet colored solution if shaken with solvent ether, organic layer shows purple color & aqueous layer
shows blue color.
• Uses:
o Sypathomimetic effects
• Bronchodilator in asthma
• In treatment of allergic conditions like hay fever
• As compared to adrenaline onset of action for ephedrine is slow, but effect is much prolonged, as it is not
quickly hydrolysed by mono amine oxidase in the body.
o Causes peripheral contraction of arterioles, therefore used to correct the low blood pressure conditions.
• Allied drugs:
o Genus Ephedra has about 45 species
o About 25 species contain ephedrine.
o Prominent species containing ephedrine are E. equisetina & E. sinica
o E. intermedia, E. major, E. helryetica & E. alata: Contain from 35- 87% of ephedrine in total alkaloids.
o The other plants containing ephedrine are Aconitum napelles (Ranunculaceae); Sida cordifolia; and S. rhombifolia
(Malvaceae); Roemeria refracta (Papaveraceae) and Taxus baccata (Taxaceae).
EPHEDRA
Alkaloidal amines, Dr. Harish Kakrani, CDCP 25
COLCHICUM
Alkaloidal amines, Dr. Harish Kakrani, CDCP 26
COLCHICUM
• Synonyms: Meadow saffron seeds, autumn crocus
• Botanical source : It consists of dried ripe seeds and fresh or dried sliced corms of Colchicum autumnale
o Family: Liliaceae.
• Geographical sources:
o Indigenous to Britain
o Grows in Central and Southern Europe
• Cultivation & Collection:
o Colchicum propagates by repeating the life cycle with the corm, which is present as a swollen
underground stem with sheathing leaves.
o Towards the end of summer, the fully grown corm develops daughter corms in the axil of scaly leaf near
the base.
o These daughter corms develop parasitically on parent corm & subsequently parent corm withers away.
o The daughter corms develop into new corms.
o May also be propagated by seeds, sown 1/8 inch deep in a bed of fine soil outdoors in August or
September; transplanting seedlings 3 inches apart when two years old; or by division of bulbs in
August. Seedling bulbs do not flower till four or five years old.
Alkaloidal amines, Dr. Harish Kakrani, CDCP 27
• Macroscopic characteristics:
1. Colchicum seeds:
o Very hard in nature
o Have a projection at hilum & from there
o develops strophiole, which is an outgrowth of testa.
o Size: 2-3mm in diameter
o Taste: bitter & acrid
o Odour: Odourless
2. Colchicum corm:
o Size: 2-3cm in diameter, 2-5mm thickness
o Fracture: Short
o Shape: sub-reniform or ovate in outline
o Color: yellowish brown
o Taste: bitter
o Odour: Odourless
COLCHICUM
Alkaloidal amines, Dr. Harish Kakrani, CDCP 28
• Microscopic characters:
1. T.S of Seed:
o Shows parenchyma & endosperm
o Parenchymatous cells are reddish brown with thick walls
o Endospermic cells show pitted walls & contain aleurone grains and fixed oils
o Strophiole portion of the seeds contain starch
2. T.S of corm:
o Corm has epidermis, parenchyma & vascular tissue
o Parenchymatous cells have abundant starch grains
o Epidermis has circular stomata
o In vascular part, the xylem vessels are spiral or annular.
• Chemical Constituents:
o SEED: 0.2-1% amino alkaloid , of which Colchicine is 0.8%
o CORMS: 0.6% Colchicine. Also contains demecolcine
o Both the alkaloids contain tropolone or cycloheptatrien-ol-one ring structure.
o Colchicine is a toxic, yellowish-white amorphour or crystalline substance that darkens on exposure
to light. It is soluble in alcohol & chloroform, sparingly soluble in water.
COLCHICUM
Alkaloidal amines, Dr. Harish Kakrani, CDCP 29
COLCHICUM
Powder characteristics of Colchicum seed powder
Alkaloidal amines, Dr. Harish Kakrani, CDCP 30
COLCHICUM
Colchicine Demecolcine
Alkaloidal amines, Dr. Harish Kakrani, CDCP 31
• Chemical tests:
o Colchicine + 60 - 70% sulphuric acid or conc. HCl yellow colour is produced.
o Alcoholic solution of colchicine + ferric chloride red color
• Uses:
o Gout & rheumatism
o Also possesses anti-tumor activity
o Used in horticulture as a chemical agent for bringing polyploidy
• Allied drugs:
o Plants bearing chemical contents similar to colchicine type of alkaloids belong to different
genera such as, Dipidax, Gloriosa, Androcybium, Camptorrhiza, etc.
o Other genera of same family liliaceae which contain colchicine- Androcybium, Bulbocodium,
Dipidax, Littonia, Fritillaria, Ornithoglossum, etc.
COLCHICUM