Alkaloids
CONTENTS
Introduction
Classification
Isolation
Purification
Biological activity
General methods of structural determination
Synthesis of alkaloids
Coniine, Nicotine, Atropine, Quinine and Morphine
INTRODUCTION
Alkaloids are a group of naturally occurring chemical compounds that
mostly contain basic nitrogen atoms.
The term alkaloid was coined by Meissner, a German pharmacist, in 1819.
Alkaloids are cyclic organic compounds containing nitrogen in a negative
state of oxidation with limited distribution among living organisms.
PROPERTIES
Most alkaloids contain oxygen in their molecular structure; those compounds are
usually colorless crystals at ambient conditions.
Some alkaloids are colored, like berberine (yellow) and sanguinarine (orange).
Most alkaloids are weak bases, but some, such as theobromine and theophylline,
are amphoteric.
Many alkaloids dissolve poorly in water but readily dissolve in organic solvents.
Most alkaloids have a bitter taste or are poisonous when ingested.
CLASSIFICATION
The alkaloids, as an important and enormously large conglomerate of naturally
occurring nitrogen containing plant substances having very specific as well as
most diversified pharmacological properties may be classified in a number of
modes and means.
i. Biosynthetic Classification
ii. Chemical Classification
iii. Pharmacological Classification
iv. Taxonomic Classification
CLASSIFICATION
i. Biosynthetic Classification
In this particular instance the significance solely lies to the precursor from which the
alkaloids in question are produced in the plant biosynthetically.
1) Indole alkaloids derived from tryptophan.
2) Piperidine alkaloids derived from lysine.
3) Pyrrolidine alkaloids derived from ornithine.
4) Phenylethylamine alkaloids derived from tyrosine.
5) Imidazole alkaloids derived from histidine.
CLASSIFICATION
ii. Chemical Classification
Here the alkaloids are classified based on the presence of the basic heterocyclic nucleus (i.e.,
the chemical entity).
1) Pyrrolidine alkaloids e.g., Hygrine
2) Piperidine alkaloids e.g., Lobeline
3) Pyrrolizidine alkaloids e.g., Senecionine
4) Tropane alkaloids e.g., Atropine
5) Quinoline alkaloids e.g., Quinine
6) Isoquinoline alkaloids e.g., Morphine
7) Aporphine alkaloids e.g., Boldine
8) Indole alkaloids e.g., Ergometrine
9) Imidazole alkaloids e.g., Pilocarpine
10) Diazocin alkaloids e.g., Lupanine
11) Purine alkaloids e.g., Caffeine
12) Steroidal alkaloids e.g., Solanidine
13) Amino alkaloids e.g., Ephedrine
14) Diterpene alkaloids e.g., Aconitine
CLASSIFICATION
iii. Pharmacological Classification
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.
1) Morphine as Narcotic analgesic
2) Quinine as Antimalarial
3) Strychnine as Reflex excitability
4) Lobeline as Respiratory stimulant
5) Boldine as Choleretics and laxatives
6) Aconitine as Neuralgia
7) Pilocarpine as Antiglaucoma agent and miotic
8) Ergonovine as Oxytocic
9) Ephedrine as Bronchodilator
10) Narceine as Analgesic (narcotic) and antitussive
CLASSIFICATION
iv. Taxonomic Classification
This particular classification essentially deals with the ‘Taxon’ i.e., the taxonomic
category.
1) Cannabinaceous Alkaloids
Ex: Hemp, Marijuana
2) Rubiaceous Alkaloids
Ex: Quinine, Katum, Kratum, Yohimbe
3) SolanaceousAlkaloids
Ex: Belladona, Sweet Peppers, Corkwood Tree, Loveapple, Tree Tobacco, Ashwagandha.
ISOLATION
a) Soxhlet Extraction Process:
The soxhlet assembly is a continuous extractor which is generally suitable for the
extraction of alkaloids from powdered plant materials with the help of organic solvents.
In this instance, the powdered drug is usually moistened with dilute ammonia solution
and then packed loosely in the thimble of the Soxhlet apparatus; and the organic solvent
affords a deep penetration of the moist drug thereby allowing the greatest possible
extraction of the alkaloids from the exposed surfaces of the cells and tissues of the crude
drug. Once, the extraction is ascertained to have completed, the solvent is filtered and
evaporated in a Rotary Thin-Film Evaporator and the residue is treated further for the
isolation of individual alkaloids.
ISOLATION
b) Stas-Otto Process:
The Stas-Otto process essentially consists of treating the powdered and sieved drug
substance with 90–95% (v/v) ethanol, previously acidified with tartaric acid. The
proportion of crude drug to solvent should be maintained as 1 Kg to 1 L. The alcohol is
distilled off under vacuum and the resulting aqueous residue is treated with petroleum-
ether (60-80°C) to remove the fatty components completely. If any alkaloid is removed
by the petroleum ether, it must be recovered by treating it with dilute mineral acid.
Thus, the resulting aqueous extract is mixed with the main bulk of aqueous extract. The
combined aqueous extract is filtered and evaporated to dryness preferably in
a Rotary Thin-Film Evaporator under vacuum. The residue is extracted with absolute
ethanol thereby dissolving the total alkaloids.
PURIFICATION
1. Direct crystallisation from solvent
2. Repeated acid base treatment
3. Chromatographic techniques
Ex: Partition, ion-exchange and column chromatography
4. Precipitation method
Ex: AuCl3, PtCl4, Mayer’s Reagent,
CHEMICAL TESTS
Dragendorff’s test: To 2–3 mL of the alkaloid solution add few drops of
Dragendorff’s reagent (potassium bismuth iodide solution). An orange
brown precipitate is formed.
Mayer’s test: To 2–3 mL of the alkaloid solution add few drops of Mayer’s
reagent (potassium mercuric iodide solution). White brown precipitate is
formed.
Wagner’s test: To 2–3 mL of the alkaloid solution add few drops of
Wagner’s reagent (iodine-potassium iodide solution). Reddish brown
precipitate is formed.
BIOLOGICAL ACTIVITY
In 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).
Source of nitrogen in case of nitrogen deficiency.
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.
BIOLOGICAL ACTIVITY
In Humans
High biological activity.
Produce vary degrees of physiological and psychological responses – largely by
interfering with neurotransmitter.
In large doses – highly toxic – fatal.
In small doses – many have therapeutic value.
Muscle relaxant, pain killers, tranquilizers, mind altering drugs, chemotherapy.
