Classification of Alkaloids: Alkaloids are a large and complex group of highly diverse natural products. In the early days, plant-derived alkaloids are used as ingredients in poison. The name “alkaloids” (Derived from Alkali) was introduced in 1819 by the German chemist Carl Friedrich Meissner. They are cyclic compounds group of compounds contain one or more basic nitrogen atoms in a heterocyclic ring. They have low molecular weight. About 25% higher plants produce alkaloids and they are procured from various parts of the plants such as all parts (E.g. Datura), Bark (E.g. Cinchona), Seeds (E.g. Nux vomica), Roots (E.g. Aconite), Leaves (E.g. Tobacco), Fruits (E.g. Black pepper), Latex (E.g. Opium), etc. Apart from this alkaloids are also obtained from animal sources like Muscopyridine from a musk of a deer, Castoramine from North America Rodent, Canadian beaver (Castor canadensis), and from bacteria sources like Pyocyanine from Pseudomonas aeruginosa. As per Ladenburg in late 1880, Alkaloid is defined as plant-derived compounds having a nitrogen-based heterocyclic ring within their molecules with basic nature. They are highly poisonous but in low doses give therapeutic activities.
- Alkaloids are crystalline but few are amorphous solids (Example: Emetine). Solid nature due to the presence of O-atom in the ring structure.
- Alkaloids are insoluble in water but soluble in most organic solvents. Caffeine, cocaine, codeine, nicotine are slightly soluble in water, Morphine, yohimbine is very slightly water-soluble.
- Alkaloids are optically active. Most of the alkaloids are laevorotatory but few are dextro-rotatory (e.g. Coniine) and few are even optically inactive, viz. papaverine.
- Alkaloids are bitter and have pronounced physiological activity.
- They have a molecular weight of between 100-900.
- They are sometimes non-volatile liquids (Examples: Hyoscine, Pilocarpine), sometimes volatile liquids (Examples: Nicotine, Coniine).
- They are generally colourless (Few are coloured such as Colchicine and Berberine are yellow, Betanidine is orange, Salt of Sanguinarine is cupper red).
- Alkaloids are naturally occurring organic compounds.
- They mostly contain basic lone pair electrons on nitrogen, hence they are basic (Some compounds like theobromine, theophylline are amphoteric).
- Alkaloids react with acids to form salts. These salts are usually freely soluble in water (Example: Quinine sulfate is water-soluble but Quinine mono-sulphate is insoluble in water) and alcohol but poorly soluble in most organic solvents (Exceptional: Scopolamine hydrobromide is soluble in organic solvents). Strong bases form a salt with weak acid and vice versa. Very weak bases form unstable salts like Caffeine, nicotine, etc.
- They form a precipitate with heavy metal iodides.
- Naturally, alkaloids exist either in a free state (as amine) or as salt with acid or alkaloid N-oxides.
- They contain one or more nitrogen in their structure and form primary amines (R-NH2; Example: Norephedrine), Secondary amines (R2-NH; Example: Ephedrine), Tertiary amines (R3-N; Example: Atropine), and Quaternary ammonium salt (R4-N; Example: d-Tubocurarine).
- They decomposed by heat but some are undergoing sublimation (E.g. Caffeine, Strychnine).
- They decomposed at a temperature above 70°C for a long time.
Classification of Alkaloids:
Broadly Alkaloids are classified in mainly four types (Fig.1)
(A) Based on Chemical Nature and Structure:
They are further classified into several types (Fig.2).
Monocyclic alkaloids: They contain a single, unfused ring. Example: Nicotine.
Bicyclic alkaloids: They consist of molecules with a 1,4 nitrogen bridged cycloheptane structure. Examples: Atropine, Cocaine.
Polycyclic alkaloids: They are having more than two rings. Examples: Strychnine, Cannabinol, Morphine, Codeine, etc.
Types of alkaloids, structures, examples, biological sources, family, and uses of some heterocyclic alkaloids are shown in Table.1.
Types of alkaloids, structure, example, biological sources, family, and uses of non-heterocyclic alkaloids are as shown in Table.2.
Based on Nature/Basicity: They are classified as:
- Primary amines (R-NH2; Example: Norephedrine),
- Secondary amines (R2-NH; Example: Ephedrine),
- Tertiary amines (R3-N; Example: Atropine)
- Quaternary ammonium salt (R4-N; Example: d-Tubocurarine).
The basicity of alkaloids is as follows: R2-NH > R-NH2 > R3-N. The basicity of alkaloids is due to the presence of lone pair of electrons on nitrogen. The basicity increases if the adjacent group is electron releasing like alkali whereas the basicity decreases if the adjacent group is electron-withdrawing like carbonyl and amide group. Hence as per basicity, alkaloids are classified as Weak bases (Example: Caffeine), Strong bases (Example: Atropine), Amphoteric (Examples: Morphine, Narceine), and Neutral alkaloid (Example: Colchicine).
Based on Hegnauer’s Classification:
- True Alkaloids: They are alkaloids that are derived directly from amino acids. They contain nitrogen in their heterocyclic ring. They are basic due to the presence of lone pair of electrons on the nitrogen atom and are strong toxic. They are also very effective. They give a positive test for common tests for alkaloids. They occur in plants either in the free state, as salts form, and as N-oxides. The primary precursors are viz. amino acids as l-ornithine, l-lysine, l-phenylalanine/l-tyrosine, l-tryptophan, and l-histidine. Examples: Quinine, Morphine, Atropine, etc.
- Proto alkaloids: They do not have nitrogen in their heterocyclic ring. They are derived from L-Tryptophan, Phenylalanine, and Tyrosine. They give a positive test for common tests for alkaloids. Examples: Ephedrine, Hordenine, Mescaline.
- Pseudo alkaloids: They are not derived from amino acids but derived from the precursors of an amino acid (Non-amino acid precursor). They have nitrogen in a heterocyclic ring (acquire nitrogen through the transamination process). The nitrogen atom is inserted into the molecule at a late stage. They do not give a positive test for common tests for alkaloids. Examples: Caffeine, Coniine, Capsaicin.
(B) Based on Pharmacological action:
Based on pharmacological activity, alkaloids are classified into various groups (Table.3).
(C) Based on Biosynthesis pathway:
They are classified as follows (Table.4):
(D) Based on Taxonomical Origin:
Alkaloids are classified based on biological sources. Examples: Quinine from the bark of Cinchona calisaya, Rauwolfia from roots of Rauwolfia serpentina, Morphine from dried latex of Papaver somniferum, etc.
- They are end products of the metabolism of waste products.
- They are storage reservoirs of nitrogen for protein synthesis.
- They act as a protective agent for the plants against attack by predators (parasites or herbivores).
- They act as plants stimulants and regulators in activities such as growth, metabolism, and reproduction.
- They act as a detoxification agent, which renders harmless certain substances, accumulation of which might cause damage to the plant.
(A) Precipitation reactions:
- Alkaloid sample reacts with Dragendorff’s reagent (Potassium-bismuth-iodide solution) which gives reddish-brown precipitate.
Reagent Composition: Bismuth nitrate: 8.00 g, Nitric acid: 21.5 g, Potassium iodide: 27.2 g, and water to make 100 ml.
- Alkaloid sample reacts with Mayer reagent (Potassium-mercuric-iodide solution) which gives cream colour precipitate.
Reagent Composition: Mercuric chloride: 1.3 g, Potassium iodide: 5.00 g, and water to make 100 ml.
- Alkaloid sample reacts with Wagner reagent (Iodine-potassium-iodide solution) which gives Brown colour precipitate.
Reagent Composition: Iodine: 1.3 g, Potassium iodide: 2.0 g, and water to make 100 ml.
- Alkaloid sample reacts with Hager reagent (Saturated solution of picric acid) which gives yellow color precipitate.
Reagent Composition: Picric acid: 1.0 g, water to make 100 ml.
- Alkaloids react with Valser’s test (Mercuric iodide) which gives a white color precipitate.
- Alkaloid sample reacts with acids and gives buff color precipitate.
- Alkaloids react with picolinic acid and give a yellow color precipitate.
(B) Important Colour reactions:
- Vitali Morin Test: This test is positive for Solanaceae family drugs such as Belladonna, Datura, Henbane, Mandrake, Tobacco, etc.
Test: Sample alkaloid mixed with fuming nitric acid, evaporated to dryness. Dissolved residue in acetone and added a methanolic solution of KOH. It produced a violet color. It indicates the presence of the tropane group.
- Van Urk’s Test: This test is positive for Ergot alkaloid.
Test: Sample reacts with para-dimethyl amino benzaldehyde and dilutes sulphuric acid and gives blue color. It indicates the presence of the indole group especially the clavinet group of alkaloids.
- Friend’s Test: This test is positive for opioid alkaloids. Sample reacts with Froehd’s reagent (sodium molybdate in concentrated sulphuric acid) and forms brownish-black color due to the presence of the Isoquinoline group.
- Thalloquin Test: This test is positive for Quinine alkaloid. Cinchona powder reacts with bromine water in presence of strong ammonia and gives an emerald green color due to the presence of the quinoline group.
- Rosequin Test: This test is also known as the Erythroquinine test. This test is positive for Quinine.
Test: Sample solution added with dilute acetic acid and a few drops of bromine water. Then added a drop of a solution of potassium ferrocyanide and added a drop of strong ammonia solution. The solution turns to red color. In this solution, a few ml of chloroform is added then the chloroform layer became red.
- Murexide Test: This test is positive for purine derivative alkaloids, mainly Caffeine.
Test: Caffeine sample is taken in China dish and added potassium chlorate and dilute HCl. Evaporated to dryness. It produces a red color. Further, exposing the China dish to strong ammonia vapor. The red color is converted into purple or violet color. When caffeine reacts with HCl it forms tetramethylalloxanthine which further in presence of ammonia forms ammonium salt of tetramethylpurpuric acid (Murexide).
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