Alkaloids : General Introduction, Occurrence /Distribution, Classification, Extraction and Chemical Test

 

What are Alkaloids?

·         Alkaloids are usually secondary metabolites.

·         The term alkaloid was coined by Meissner in 1819. Alkaloids are  “alkali like” substances / organic compounds.

·         They are basic nitrogen containing compound obtained from plant, animal and microorganism having marked physiological action.

·         They are basic in nature; they contain one or more nitrogen atom (usually in heterocyclic ring).

·         First synthesized alkaloid was connine.

Define the term Alkaloids.

Alkaloids are complex organic compounds of natural or synthetic origin which are basic in nature and contains one or more nitrogen atom, normally of heterocyclic nature and possess specific pharmacological activity on human or animal body, when used in small quantity.

Discuss the distribution of Alkaloids in the plant kingdom?

·         Rare in lower plants.

·         Dicots are richer in alkaloids than Monocots.

·         Families rich in Alkaloids: Apocynaceae, Rubiaceae, Solanaceae and Papaveraceae.

·         Families free from Alkaloids: Rosaceae, Labiatae.

·         They found in different parts of the plant:

ü  All Parts e.g. Datura

ü  Barks e.g. Cinchona

ü  Seeds e.g. Nux vomica

ü  Roots e.g. Aconite

ü  Fruits e.g. Black pepper

ü  Leaves e.g. Tobacco

ü  Latex e.g. Opium

Name the different forms in which alkaloids found in Plants.

—  In the form of Free bases e.g. Caffeine

—  Salts with Organic acids e.g. Oxalic, Acetic acid.

—  Salts with inorganic acids e.g. HCl, H₂SO₄

—  Salts with special acids: Meconic acid in Opiumin, Quinic acid in Cinchona.

—  Glycosidal form e.g. Solanine in Solanum.

Discuss the role / functions of Alkaloids in Plants.

Alkaloids are doing following functions in the plants:

—  They may act as protective against insects and herbivores due to their bitterness and toxicity.

—  They are, in certain cases, the final products of detoxification (waste products).

—  As a source of nitrogen in case of nitrogen deficiency.

—  As a Carrier: For transportation of different acids.

—  They, sometimes, act as growth regulators in certain metabolic systems.

—  They may be utilized as a source of energy in case of deficiency in carbon dioxide assimilation.

Explain the various physical and chemical properties of the alkaloids.

1.      Physical Properties

A. Condition:

—  Most alkaloids are crystalline solids.

—  Few alkaloids are amorphous solids e.g. emetine.

—  Some are liquids that are either:

ü  Volatile e.g. nicotine and coniine.

ü  Non-volatile e.g. pilocarpine and hyoscine.

B. Colour:

The majority of alkaloids are colorless but some are colored e.g.: Colchicine and berberine are yellow.

Canadine is orange.

C. Solubility:

—  Both alkaloidal bases and their salts are soluble in alcohol.

—  Generally, the bases are soluble in organic solvents and insoluble in water

Exceptions:

ü  Bases soluble in water: caffeine, ephedrine, codeine, colchicine, pilocarpine and quaternary ammonium bases.

ü  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:

ü  Salts insoluble in water: Quinine monosulphate.

ü  Salts soluble in organic solvents: Lobeline and apoatropine hydrochlorides are soluble in chloroform.

 

2.      Chemical Properties

·         Alkaloids are basic in nature (Lone pair of electrons on nitrogen)

·         Basicity increased when adjacent functional group are electron releasing.

Primary amines R-NH2 e.g. Norephedrine

Secondary amines R2-NH e.g. Ephedrine

Tertiary amines R3-N e.g. Atropine

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

·         Basicity order:  R2-NH > R-NH2 > R3-N

·         Saturated hexacyclic amines are more basic than aromatic amines.

·         Bases sensitive to decomposition whereas salts are stable.

Isomerisation:

—  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 antiarrhythmic.

—   The racemic (optically inactive) dl-atropine is physiologically active.

Give the general classification of Alkaloids?

There are three main types of alkaloids: (1) true alkaloids, (2) protoalkaloids, and (3) pseudoalkaloids. True alkaloids and protoalkaloids are derived from amino acids, whereas pseudoalkaloids are not derived from these compounds.

A.   True Alkaloids

 

·         True alkaloids derive from amino acid and they contain 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.

·         Moreover, most of them are well-defined crystalline substances which unite with acids to form salts. True alkaloids may occur in plants (1) in the free state, (2) as salts and (3) as N-oxides.

·         These alkaloids occur in a limited number of species and families, and are those compounds in which decarboxylated amino acids are condensed with a non-nitrogenous structural moiety.

·         The primary precursors of true alkaloids are such amino acids as L-ornithine, L-lysine, L-phenylalanine/L-tyrosine, L-tryptophan and L-histidine.

·         Examples of true alkaloids include such biologically active alkaloids as cocaine, quinine, dopamine and morphine.

 

B.    Proto-alkaloids / Amino Alkaloids

 

·         Proto-alkaloids are compounds, in which the N - atom derived from an amino acid and is not a part of the heterocyclic.

·         They are derived from L-tyrosine and L-tryptophan.

·         Proto-alkaloids are those with a closed ring, being perfect but structurally simple alkaloids.

·         Examples: Ephedra, Colchicum etc.

 

C.   Pseudoalkaloids

 

·         Pseudoalkaloids are compounds, the basic carbon skeletons of which are not derived from amino acids.

·         In reality, pseudoalkaloids are connected with amino acid pathways. They are derived from the precursors or post-cursors (derivatives the in-degradation process) of amino acids.

·         They can also result from the amination and transamination reactions of the different pathways connected with precursors or post-cursors of amino acids.

·         These alkaloids can also be derived from non-amino acid precursors.

·         The N atom is inserted into the molecule at a relatively late stage, for example, in the case of steroidal or terpenoid skeletons.

·         Examples of pseudoalkaloids include such compounds as coniine, capsaicin, ephedrine, solanidine, caffeine and theobromine.

 Give the Chemical classification of Alkaloids?

Alkaloids are mainly divided into two categories on the basis of their chemical structure, that is, heterocyclic rings.

 Atypical alkaloids

 These are also known as nonheterocyclic alkaloids and contain nitrogen in aliphatic chain.

Typical alkaloids

 These are also known as heterocyclic alkaloids and contain nitrogen in heterocyclic ring system.

 

For detailed classification and structure of basic nucleus refer: https://en.wikipedia.org/wiki/Alkaloid

Discuss the classification of Alkaloids based on biosynthetic origin.

Different metabolic pathways are involved in the biosynthesis of alkaloids. It is important to know precursor / starting material from which the alkaloids in question are produced in the plant biosynthetically. It is quite convenient and also logical to group together all alkaloids having been derived from the same precursor but possessing different taxonomic distribution and pharmacological activities.

Examples

(i) Indole alkaloids derived from tryptophan.

(ii) Piperidine alkaloids derived from lysine.

(iii) Pyrrolidine alkaloids derived from ornithine.

(iv) Phenylethylamine alkaloids derived from tyrosine.

(v) Imidazole alkaloids derived from histidine.

It is, however, pertinent to mention at this juncture that the enormous volume of authentic information accumulated so far with regard to the isolation of alkaloids from a variety of plant species and their subsequent characterization by the help of latest analytical techniques they may be classified as follows:

A. Alkaloids derived from Amination Reactions

(i) Acetate-derived Alkaloids

(ii) Phenylalanine-derived Alkaloids

(iii) Terpenoid Alkaloids

(iv) Steroidal Alkaloids

B. Alkaloids derived from Anthranilic Acid

(i) Quinazoline Alkaloids

(ii) Quinoline Alkaloids

(iii) Acridine Alkaloids

C. Alkaloids derived from Histidine

Imidazole Alkaloids

D. Alkaloids derived from Lysine

(i) Piperidine Alkaloids

(ii) Quinolizidine Alkaloids

(iii) Indolizidine Alkaloids

E. Alkaloids derived from Nicotinic Acid

Pyridine Alkaloids

F. Alkaloids derived from Ornithine

(i) Pyrrolidine Alkaloids

(ii) Tropane Alkaloids

(iii) Pyrrolizidine Alkaloids

G. Alkaloids derived from Tyrosine

(i) Phenylethylamine Alkaloids

(ii) Simple Tetrahydro iso-quinoline Alkaloids

(iii) Modified Benzyl Tetrahydro iso-quinoline Alkaloids

H. Alkaloids derived from Tryptophan

(i) Simple Indole Alkaloids

(ii) Simple b-Carboline Alkaloids

(iii) Terpenoid Indole Alkaloids

(iv) Quinoline Alkaloids

(v) Pyrroloindole Alkaloids

(vi) Ergot Alkaloids

 

Discuss the classification of Alkaloids based on their major pharmacological activity.

Interestingly, the alkaloids exhibit a broad range of very specific pharmacological characteristics. Perhaps this might also be used as a strong basis for the general classification of the wide-spectrum of alkaloids derived from the plant kingdom, such as: analgesics, cardio-vascular drugs, CNS-stimulants and depressants, dilation of pupil of eye, mydriatics, anticholinergics, sympathomimetics, antimalarials, purgatives, and the like. However, such a classification is not quite common and broadly known.

Examples

(i) Morphine as Narcotic analgesic;

(ii) Quinine as Antimalarial;

(iii) Strychnine as Reflex excitability;

(iv) Lobeline as Respiratory stimulant;

(v) Boldine as Choleretics and laxatives;

(vi) Aconitine as Neuralgia;

(vii) Pilocarpine as Antiglaucoma agent and miotic;

(viii) Ergonovine as Oxytocic;

(ix) Ephedrine as Bronchodilator;

(x) Narceine as Analgesic (narcotic) and antitussive.

 Explain the methods of extraction of Alkaloids from crude drug material.

The extraction of alkaloids is based on their basic character and solubility profiles. Generally, alkaloids are extracted mainly using two methods.

1.    Stass-Otto Method

• The powdered material that contains alkaloidal salts is moistened with alkaline substances like sodium bicarbon-ate, ammonia, calcium hydroxide, etc., which combines with acids, tannins and other phenolic substances and sets free the alkaloids bases. 
• Extraction is then carried out with organic solvents such as ether or petroleum spirit. 
• The concentrated organic liquid is then shaken with aqueous acid and allowed to separate. 
• Alkaloid salts will be present in aqueous liquid, while many impurities remain behind in the organic liquid.

 

Manskes Method

• The collected powdered material is extracted with water or aqueous alcohol containing dilute acid. 
• Chloroform or other organic solvents are added and shaken to remove the pigments and other unwanted materials. 
• The free alkaloids are then precipitated by the addition of excess alkalis like, sodium bicarbonate or ammonia and separated by filtration or by extraction with organic solvents.

Volatile liquid alkaloids (nicotine and coniine) are isolated by distillation. The powdered material that contains alkaloids is extracted with water and the aqueous extract is made alkaline with sodium carbonate or ammonia and the alkaloid is distilled off in steam. This could be collected and purified.

 Discuss the general chemical tests used for the identification of Alkaloids.

The chemical tests are performed from neutral or slightly acidic solution of drug.

 Dragendorff’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.

 Tannic Acid Test

 Drug solution + few drops of tannic acid solution, formation of buff coloured precipitate.

 Ammonia Reineckate Test

 Drug solution + slightly acidified (HCl) saturated solution of ammonia reineckate, formation of pink flocculent precipitate.