Mr. A.R.

Surana
Assistant professor S.M.B.T. College of Pharmacy, Nashik-422403
8/23/2013

Alkaloids
Definition:
the term alkaloid (alkali-like) is commonly used to designate basic heterocyclic nitrogenous compounds of plant origin that are physiologically active. Derived from amino acids.

DEVIATION FROM DEFINITION:

Basicity: Some alkaloids are not basic e.g. Colchicine, Piperine, Quaternary alkaloids. Nitrogen: The nitrogen in some alkaloids is not in a heterocyclic ring e.g.

Ephedrine, Colchicine, Mescaline.

Plant Origin: Some alkaloids are derived from Bacteria, Fungi, Insects, Frogs, Animals. Biosynthesis: Some alkaloids are not derived from amino acids e.g purine, steroidal alkaloid .

QUALITATIVE CHEMICAL TESTS FOR ALKALOIDS

General tests answered by all alkaloids are as follows:

1. Dragendorffs test: To 23 mL of the alkaloid solution add few drops of

Dragendorffs reagent (potassium bismuth iodide solution). An orange brown precipitate is formed. 2. Mayers test: To 23 mL of the alkaloid solution add few drops of Mayers reagent (potassium mercuric iodide solution). White brown precipitate is formed. 3. Hagers test: To 23 mL of the alkaloid solution add few drops of Hagers reagent (saturated solution of picric acid). Yellow precipitate is formed.

4. Wagners test: To 23 mL of the alkaloid solution add few drops of Wagners

reagent (iodine potassium iodide solution). Reddish brown precipitate is formed.

Physical Properties:
I- State:
Most alkaloids are crystalline solids. Few alkaloids are amorphous solids e.g. emetine. Some are liquids that are either: Volatile e.g. nicotine and coniine, or Non-volatile e.g. pilocarpine and hyoscine. II- Color:

The majority of alkaloids are colorless but some are colored e.g.:
Colchicine and berberine are yellow. betanidine is orange. The salts of sanguinarine are copper-red.

III- Solubility: Both alkaloidal bases and their salts are soluble in alcohol. Generally, the bases are soluble in organic solvents and insoluble in water Exceptions: Bases soluble in water: caffeine, ephedrine, codeine, colchicine, pilocarpine and quaternary ammonium bases. Bases insoluble or sparingly soluble in certain organic solvents: morphine in

ether, theobromine and theophylline in benzene.

Salts are usually soluble in water and, insoluble or sparingly soluble in organic solvents. Exceptions: Salts insoluble in water: quinine monosulphate. Salts soluble in organic solvents: lobeline and apoatropine hydrochlorides are soluble in chloroform

IV- Isomerization:
Optically active isomers may show different physiological activities. l-ephedrine is 3.5 times more active than d-ephedrine. l-ergotamine is 3-4 times more active than d-ergotamine. d- Tubocurarine is more active than the corresponding l- form. Quinine (l-form) is antimalarial and its d- isomer quinidine is antiarrythmic. The racemic (optically inactive) dl-atropine is physiologically active.

Chemical Properties
Most of the alkaloids are basic in nature, due to the availability of lone pair of electrons on
nitrogen. The basic character of the alkaloid compound is enhanced if the adjacent functional groups are electron releasing. The alkaloid turns to be neutral or acidic when the adjacent functional groups are electron withdrawing like amide group which reduces the availability of the lone pair of electron. Their salt formation with an inorganic acid prevents many a time their decomposition.

In the natural form, the alkaloids exist either in Free State, as amine or as salt with acid or
alkaloid N-oxides. The alkaloid may contain one or more nitrogen and exist in the form of Primary amines R-NH2 e.g. Norephedrine e.g. Ephedrine e.g. Atropine

Secondary amines R2-NH Tertiary amines R3-N

Quaternary ammonium salts R4-N e.g d-Tubocurarine

Distribution in Plant
All Parts e.g. Datura.

Barks e.g. Cinchona

Seeds e.g. Nux vomica Roots e.g. Aconite Fruits e.g. Black pepper Leaves e.g. Tobacco Latex e.g. Opium

Extraction of alkaloids 1. Stass otto method

Powdered plant material Defatted with non-polar solvent Defatted plant material

Moist with water and treated with NH3, Dil. Lime solution (Free Alkaloid) Extracted with organic solvent like chloroform, ether Extract, Concentrate it

Dissolved in Dil. Acid (Alkaloidal salt)

Aqueous phase

Organic phase impurities

Basified with ammonia or sodium Bi-carbonate or Dil. KOH

Aqueous phase

Organic phase(Free Alkaloid)

Evaporate to dryness

Crude Alkaloids

Extraction of alkaloids 2. Manskes method

Powdered Crude material Defatted with non-polar solvent Defatted Crude material Extract with methanol Methanol Extract Concentrate Dissolve in water and Acidified it upto pH 2 (Alkaloidal salt)

Steam Distillation to remove traces of methanol

Stand for several days in refrigerator OR boiled with paraffin Filter Filtrate Shake with organic solvent like chloroform or ether

Aqueous phase (Alkaloidal salt)

Organic phase

Basified with ammonia or sodium Bi-carbonate or Dil. KOH

Aqueous phase

Organic phase

Evaporate to dryness

Crude Alkaloids

Purification of Alkaloids
1. Direct crystallization from solvent 2. Repeated acid base treatment 3. Fractional crystallization
Ephedrine & Pseudoephedrine Oxalates
Crystallization from water

Atropine & Hyoscyamineine Oxalates

Crystallization from Acetone/Ether

Ephedrine Oxalate Crystals

Pseudoephedrine Oxalate Solution

Atropine Oxalate Crystals

Hyoscyamine Oxalate Solution

4. Chromatographic techniques 5. Gradient pH technique

Classification of alkaloids

Chemical classification
A) True alkaloids
Sr. no. 1. Type Pyrrole and pyrrolidine Pyiridine and piperidine
N N H

Structure
N H N H

Examples e.g. Hygrine, coca species

2.

e.g. Arecoline, anabasine, lobeline, conine, trigonelline e.g. Echimidine, senecionine, seneciphylline e.g. Atropine, hyoscine, hyoscyamine, cocaine, pseudopelletirine e.g. Quinine, quinidine, cinchonine, cupreine, camptothecine

3. 4. 5.

Pyrrolizdine
N

Tropane Quinoline

N
6. Isoquinoline
N

e.g.Morphine, codeine, emetine, cephaline, narcotine, narceine, dtubocurarine

Indole
N H
N H

e.g. Erotamine, ergotametriene, reserpine, vincristine, vinblastine, strychnine, brucine e.g. Pilocrpine, isopilocarpine, pilosine

Imidazole

Norlupinane

e.g. Cystisine, laburinine

N
10 Piporphine (reduced isoquinoline napthalene)
N

e.g. Boldine

1.

Alkyalamine

B) PROTOALKALOID Ephedrine, Pseudoephedrine

HO NH

C) Pseudoalkaloid
1. Purine

N HN

N N

e.g. Caffeine, thophylline, theobromine

2.

Steroidal

e.g. Solanidine, conessine, protoveratrine

3.

Diterpene

C20H32

e.g. Aconitine, aconine, hypoaconine

Biosynthetic classification
1. Ornithine derived alkaloids
e.g. Pyrrolidine alkaloid-nicotine Tropane alkaloid Atropine, hyosyamine, coacaine 2. Lysine derived alkaloids

e.g. Piperidine and pyridine alkaloid conine, lobaline, arecoline

Quinazolidine alkaloid- lupinine 3. Tyrosine derived alkaloids e.g. Isoquinoline alkaloid morphine, codeine, emetine, cephaline, berberine, d- tubocurine

Amino alkaloid- colchicine

4. Tryptophan derived alkaloids e.g. Indole alkaloid- ergot alkaloid, vincristine, vinblastine, reserpine, strychnine, physostigmine, strychinine, brucine

Quinoline alkaloid cinchonine, quinine, quinidine, camptothecin

5. Histidine derived alkaloids e.g. Imidazole alkaloid Pilocrpine 6. Phenylalanine derived alkaloids

e.g. Amino alkaloid- Ephedrine

Pharmacological classification
1.
2. 3. 4. 5. 6. 7.

Narcotic analgesic e.g.Morphine

Antimalerial e.g. Quinine Reflux excitability e.g.Strychnine Respiratory stimulant e.g.Lobeline Neuralgia e.g. Aconitine Oxytocic e.g. Erogotometrine Bronchodilator e.g. Ephedrine, vasicine

8.
9.

Anticholinergic e.g. Atropine

CNS stimulant e.g. Caffeine

10. Antitussive e.g. Codeine 11. Antiarrythmic e.g.Quinidine 12. Antihypertensive e.g. Reserpine 13. Anticancer e.g. Vincristine 14. Antiglucoma e.g. Pilocarpine

Biosynthesis of indole alkaloids

Biosynthesis of Isoquinoline alkaloids

Biosynthesis of Tropane alkaloids

Biosynthesis of Quinoline alkaloids