ALKALOIDS INTRODUCTION
The definition of alkaloids is not simple and precise and sometimes it is difficult to distinguish the thin line between alkaloids and other natural nitrogen containing metabolites.
Natural nitrogen containing compound are:
o Amino acids
o Amines
o Alkaloids
o Indole
o Purines, pyrimidines and cytokinins
o Cyanogenetic glycosides
o Chlorophylls
alkaloid is an organic compound of natural origin which contains nitrogen atom.
Pseudo alkaloids most often have all of the characteristics of the true alkaloid but they are not derived from amino acids. Some of the most known examples are Isoprenoid, Aconite, Aconine, Hypoaconitine etc.
Proto alkaloids are simple amines in which the nitrogen atom is not part of heterocyclic ring. They are basic in nature and derived from amino acids. Few examples of these are Colchicine, Ephedrine and Pseudo ephedrine.
Alkaloids occur exceptionally in bacteria (Pseudomonas aeruginosa) and rather rarely in fungi (Psilocin from the hallucinogenic mushroom).
In the plant, alkaloid occurs as soluble salt (citrate, Malate, tartarate, melonates,benzoates, isobutyrates) or in combination with tannins.
They are often localized in peripheral tissue external layer of the bark and root or seed tegument. Alkaloids synthesis takes place at specific sites (growing root, chloroplast, laticiferous cell).
FUNCTIONS OF ALKALOIDS
They are reserve substances which can supply nitrogen.
They might be the defensive mechanism for plant growth in dry region to protect from grazing animals, herbivores and insects.
They may be end product of detoxification mechanism in plant and by this way check formation of substance which may be prove to harmful to the plant.
The possible role as growth regulatory factor in the plant.
They are present normally in conjugation with plant acid like mercuric acid, cinchotannic acid etc. Therefore alkaloids could be acting as carriers within plant for transportation of such acids.
PHYSICOCHEMICAL PROPERTIES
• Alkaloids have molecular weight from 100-900.
• Although most of the bases that do not contain oxygen atom are liquid at ordinary temperature (examples: nicotine, coniine). Those that do contain oxygen atom are
normally crystallisable solids and in rare cases they are coloured compound (example berberine).
• Almost all of the crystallized bases rotate the plane of polarized light and have melting points without decomposition especially below 200⁰C.
• As a general rule alkaloids as bases are not soluble in water. They are soluble in polar or slightly polar organic solvents.
• The basicity of alkaloids varies greatly. Since this property depends entirely on the availability of the lone pair of electron on the nitrogen atom.
• Electron withdrawing group in close proximity to the nitrogen atom decrease the basicity, whereas electron donating group enhances it.
• The basic character allows the formation of salts with mineral acids (i.e. hydrochloride, sulphates, and nitrates) and organic acids (i.e. tartarate, sulfonate).
• Alkaloidal salts are generally soluble in water and in dilute alcohols and they are except in rare cases not soluble in organic solvent.
• Pseudo alkaloids and proto alkaloids show higher solubility in water while free bases of alkaloids are soluble in organic non polar immiscible solvent.
DETECTION
• Mayer reagent (Potassium mercuric iodide solution) gives cream coloured precipitate.
• Dragendorff reagent (Potassium bismuth iodide solution) shows reddish brown precipitate.
• Wagner reagent (Iodine potassium Iodide solution) yields reddish brown precipitate.
• Hagers reagent (saturated Picric acid solution) gives yellow colour precipitate.
CLASSIFICATION OF ALKALOIDS
1. Pharmacological Classification
Depending on the physiological response the alkaloids are classified under various pharmacological categories like CNS stimulants or depressant, sympathomimetics,
analgesics, purgatives etc. Main drawback of this system is that it does not take into consideration about chemical nature of crude drug. Within the same drug the individual
alkaloids may exhibit different action.
Example-
1) Morphine is narcotic and analgesic while codeine is mainly antitussive.
2) Cinchona quinine is antimalarial whereas quinidine is cardiac
depressant.
2.Taxonomic Classification
This method classifies the vast number of alkaloids based on their distribution in various plant families like solanaceous alkaloids in solanaceae family or papillionaceous alkaloids in papillionaceae family. The grouping of alkaloids are done as per the name of genus in which
they occur e.g. Ephedra, cinchona etc. The chemotaxonomic classification has been further
derived from this classification.
3. Biosynthetic Classification
This method gives the significance to the precursor from which the alkaloids are biosynthesized in the plant. Hence the variety of alkaloid with different taxonomic distribution and physiological activities can be brought under some group if they are
derived from same precursor i.e. all indole alkaloid from tryptophan are grouped together.
Alkaloidal drugs are categorised on the fact whether they are derived from amino acids precursor as ornithine, lysine, phenylalanine, tryptophan etc.
4. Chemical Classification
This is the most accepted way of classification of alkaloids which basically depends on ring structure present in the alkaloid. The alkaloidal drugs are broadly categorized into two divisions:
• True alkaloids (subdivided into 12 groups).
• Proto alkaloids or biological amines and pseudo alkaloids.
(a) True alkaloids
1. Pyrrole and pyrrolidine: Hygrine, coca species.
2. Pyridine and piperidine: Arecoline, Anabasine, coniine, trigonelline.
3. Pyrrolizidine: Echimidine, symphitine.
4. Tropane (piperidine/N-methyl pyrrolidine): Atropine, hyoscine.
5. Quinoline: Quinine, Quinidine, Chinchonine.
6. Isoquinoline: Morphine, codeine.
7. Aporphine (reduced isoquinoline - Naphthalene): boldine.
8. Indole (Benzpyrole): Vincristine, Ergometrine, Reserpine.
9. Imidazole: Pilocarpine, Isopilocarpine.
10. Norlupiname: Cytisine, Spartine.
11. Purine (pyrimidine/ imidazole): Caffine/ theofronine, theophylline.
12. Steroidal (cyclo pentano per hydro phenathrene ring): Solanidine, Conessine.
(b) Pseudo alkaloids
Diterpenes- Aconitine, Aconine
(c) Proto alkaloids
Alkylamines (amino alkaloids) – Ephedrine, colchinine