alkaloidal amines

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.


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.


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


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


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


1

Alkaloidal amines (proto-

alkaloids)

Colchicine Colchicum autumnale Antimitotic, uric acid amines solvent

Ephedrine Ephedra sinica Sympathetic stimulant,bronchodilator

Mescaline Lophophora williamsii Hallucinogenic



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


AMINO-ALKALOIDS

(PROTO-ALKALOIDS)


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.


BIOSYNTHESIS OF AMINO ALKALOIDS

Dehydration

3- dehydroShikimic acid

SHIKIMIC ACID


Shikimicacid

Dehydration

Shikimic acid-3- phosphate

Phosphoenol pyruvic acid

5- enolpyruvyl shikimate-3- phosphate

CHORISMIC ACID

Prephenicacid

Phenyl pyruvic acid

PHENYL ALANINE




Phenyl alanine

Ephedrine (Ephedrine spp.)

Colchicine(Colchicum autumnale)


GENERAL PHARMACOLOGICAL ACTION & USES OF AMINO- ALKALOIDS

• Cause

– Dilation of the bronchi (asthma),

– Increase heart rate and

– Peripheral vasoconstriction


EPHEDRA


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


• 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


Macroscopical characteristics of

Ephedra Stem &

Leaves

EPHEDRA


• 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


• 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


EPHEDRA

Powder characteristics of Ephedra stemTransverse Section of Ephedra Stem


• 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


• 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


COLCHICUM


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.


• 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


• 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


COLCHICUM

Powder characteristics of Colchicum seed powder


COLCHICUM

Colchicine Demecolcine


• 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

alkaloidal amines

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