Drugs of Abuse MODULE No.33: Alkaloids SUBJECT FORENSIC SCIENCE

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SUBJECT FORENSIC SCIENCE
Paper No. and Title PAPER No. 9: Drugs of Abuse
Module No. and Title MODULE No. 33: Alkaloids
Module Tag FSC_P9_M33

FORENSIC SCIENCE PAPER No.9: Drugs of Abuse
MODULE No.33: Alkaloids
TABLE OF CONTENTS
1. Learning Outcomes
2. Introduction
3. Forensic Significance
4. Chemical Properties of Alkaloids
5. Classification of Alkaloids
6. Some Notable Alkaloids of Forensic Importance
7. Summary

FORENSIC SCIENCE PAPER No.9: Drugs of Abuse
MODULE No.33: Alkaloids
1. Learning Outcomes
After studying this module, you shall be able to know about-
 The significance of Alkaloids
 Classification of Alkaloids and importance of some notable Alkaloids
 Forensic importance and examination of Alkaloids

2. Introduction
Alkaloids are a group of molecules with a comparatively large occurrence in nature around
the world. They are very diverse chemicals and biomolecules, but they are completely
secondary compounds and they are derivative of amino acids. However, an exact definition
of the word ‘alkaloid’ (alkali-like) is slightly difficult because there is no clear-cut borderline
between alkaloids and naturally occurring complex amines. The term alkaloid was coined in
1819 by the pharmacist W. Meisner and meant simply, alkali like. Typical alkaloids are
derived from plant sources, they are basic, they comprehend one or more nitrogen atoms,
generally existing in a heterocyclic ring, and they habitually have a noticeable physiological
action on human or other animals. The term ‘proto-alkaloid’ or ‘amino-alkaloid’ is
occasionally applied to compounds such as hordenine, ephedrine and colchicine which lack
one or more of the properties of typical alkaloids. Alkaloids are organic bases.
A “True Alkaloid” can be regarded as by:
 The possession of a nitrogen atom as part of a heterocyclic system;
 A multifaceted molecular structure;
 Significant pharmacological properties;
 Its origin from the plant kingdom
The majority of alkaloids fit this four part definition; however, a number of exceptions exist.
The compounds Samandarine, Samandarone, and Cycloneosamandarine, secluded from the
dermal glands of the European Fire Salamander displays the usual properties of an alkaloid
substance, but do not fit the definition of a “true alkaloid” owing to their animal origin. True
alkaloids are of rare occurrence in lower plants. In the fungi the lysergic acid derivatives and
the sulphur-containing alkaloids, e.g. the gliotoxins, are the best known. Many alkaloids are
poisonous, others are addictive (e.g. cocaine), and some are used clinically (e.g. morphine).
More than 10,000 alkaloids are currently known, the first discovered being Narcotine,
isolated from opium.
FORENSIC SCIENCE PAPER No.9: Drugs of Abuse
MODULE No.33: Alkaloids
Alkaloids are constituents very well recognized for their biological action at the
commencement of world evolution. They were used in traditional herbal medication for the
treatment of ailments and in weapons as venoms in the course of tribal wars and during
hunting. After the discovery of the first alkaloid, narcotine, other alkaloids were rapidly
discovered like Morphine form opium, strychnine from Strychnos nux-vomica seeds, emetine
from ipecacuanha root, quinine from Cinchona bark and coniine from hemlock. Alkaloids are
used medicinally in their own right e.g. hyoscyamine and vinblastine and they have often
provided lead compounds for the development of synthetic drugs. For example, cocaine was
the first local anaesthetic, quinine the first antimalarial and tubocurarine the first
neuromuscular blocking agent. Alkaloids frequently have powerful physiological effects.
Most alkaloids are colourless, crystalline compounds: e.g. coniines, but some such as nicotine
and hygrine, are liquids. Usually, many are optically active in nature and the various active
forms are generally found but not in different plants. Alkaloids are produced by secondary
metabolism of primary metabolites, usually amino acids. These pathways are long, intricate,
stereochemically precise and energy consuming, and are assumed to be of evolutionary
benefit.

3. Forensic Significance
The poisonous and therapeutic effects of plants have been known since time immemorial, but
the active constituents have been studied for only about 200 years. In most human history,
alkaloids from plant extracts have been used as ingredients in potions (liquid medicine) and
poisons. Ancient people used plant excerpts containing alkaloids for the treatment of a large
number of diseases such as snakebite, fever and insanity. Habitually the bioactive compounds
in the plants that intrigue the chemist are the nitrogen containing bases called alkaloids.
Alkaloids have complex molecule structure and they have significant pharmacology
activities. Alkaloids are time and again toxic to man and have many intense physiological
actions, hence their wide used in medicine. For examples, cinchona alkaloids which, is
existing in the bark of Cinchona species and Remijia species consisted of quinine as their
main constituents which has been known as anti- malarial agent. Alkaloids have delivered a
means of pharmacologically active compounds. Approximately 25% of the drugs used at
present are of plant origin. These are administered either as pure compounds or as extracts
and have often served as model structures for synthetic drugs.

FORENSIC SCIENCE PAPER No.9: Drugs of Abuse
MODULE No.33: Alkaloids
4. Chemical Properties of Alkaloids
Maximum alkaloids are well-defined crystalline substances which bond with acids to form
salts. In the plant they may exist in the free- state, as salts or as N -oxides. In addition to the
elements carbon, hydrogen and nitrogen, most alkaloids contain oxygen. A small number of
alkaloids, such as coniine from hemlock and nicotine from tobacco, are oxygen-free and are
liquids. Even if coloured alkaloids are comparatively uncommon, they are not unknown;
berberine, for example, is yellow and the salts of sanguinarine are copper-red.

5. Classification of Alkaloids

5.1 CLASSIFICATION BASED UPON THE BIOGENESIS:
Alkaloids show great variety in their botanical and biochemical origin, in chemical structure
and in pharmacological action. Consequently, many different systems of classification are
possible and the classification mentioned hereinafter is not exhaustive. Alkaloids can be
classified by their mutual molecular precursors, founded on the biological pathway used to
build the molecule. From a structural perspective, alkaloids are separated according to their
shapes and origins. There are three main types of alkaloids:
(1) True alkaloids (2) Protoalkaloids (3) Pseudoalkaloids

True alkaloids and Protoalkaloids are derived from amino acids, whereas pseudoalkaloids are
not derived from these compounds.
5.1.1 True alkaloids
True alkaloids are derived from amino acids and they share a heterocyclic ring with nitrogen.
These alkaloids are extremely reactive substances with biological activity even in small
doses. All true alkaloids have a bitter taste and appear as a white solid, with the exception of
nicotine which is a brown liquid. True alkaloids form water-soluble salts. Furthermore, most
of them are crystalline substances which bond with acids to form salts.

FORENSIC SCIENCE PAPER No.9: Drugs of Abuse
MODULE No.33: Alkaloids
True alkaloids may occur in plants in the Free State, as salts and as N-oxides. These alkaloids
befall in a narrow sum of species and families, and are those compounds in which
decarboxylated amino acids are condensed with a non-nitrogenous structural moiety. They
are typically found as salts in plant such as liriodenine and morphine.

5.1.2 Protoalkaloids
Protoalkaloids are compounds, in which the N atom derived from an amino acid is not a
fragment of the heterocyclic ring. Such kinds of alkaloid include compounds derived from l-
tyrosine and l-tryptophan. Protoalkaloids are of a closed ring, being impeccable but
structurally simple alkaloids. They are not restricted to any specific class of alkaloids and are
often classified according to the amino acids from which they are derived. They form a
minority of all alkaloids. Hordenine, mescaline and yohimbine are good examples of these
kinds of alkaloid.

5.1.3 Pseudoalkaloids
Pseudoalkaloids are compounds of elementary carbon skeletons of which are not derived
from amino acids. They can also result from the amination and transamination reactions of
the different pathways coupled with precursors or post-cursors of amino acids. These
alkaloids can also be derived from non-amino acid precursors. The N atom is introduced into
the molecule at a relatively late stage, for example, in the case of steroidal or terpenoid
skeletons. Pseudoalkaloids can be acetate and phenylalanine derived or terpenoid, as well as
steroidal alkaloids. Examples of pseudoalkaloids include such compounds as coniine,
capsaicin, ephedrine, solanidine, caffeine, theobromine and pinidine.

5.2 CLASSIFICATION BASED UPON THE RING SYSTEM
It is perhaps the most extensively established and mutual approach of classification of
alkaloids for which the principal condition is the presence of the basic heterocyclic nucleus.
According to this concept, the alkaloids are classified on the basis of the ring system present
in them.

FORENSIC SCIENCE PAPER No.9: Drugs of Abuse
MODULE No.33: Alkaloids
5.2.1 PYRROLIDINE ALKALOIDS
Pyrrolidine alkaloids have a pyrrolidine (C N skeleton) nucleus. The structural α of these
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alkaloids is l-ornithine (in plants) and l-arginine (in animals). e.g., Hygrine

Pyrrolidine Ring System

5.2.2 PIPERIDINE ALKALOIDS
Piperidine alkaloids contain the piperidine nucleus. True piperidine alkaloids have one-
cycle compounds with the C N nucleus. One of the characteristics of piperidine alkaloids
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is the Odour. Moreover, they are neurotoxins which have acute effects such as chronic
toxicity. e.g., Lobeline

Piperidine Ring System

FORENSIC SCIENCE PAPER No.9: Drugs of Abuse
MODULE No.33: Alkaloids
5.2.3 PYRROLIZIDINE ALKALOIDS
The pyrrolizidine nucleus is characteristic of this group of alkaloids. e.g., Senecionine

Pyrrolizidine Ring System

5.2.4 TROPANE ALKALOIDS
Tropane alkaloids have a tropane (C4N skeleton) nucleus. Structurally, these alkaloids
synthesize as post-cursors of pyrrolines. Characteristic tropane alkaloids (e.g., atropine,
hyoscyamine, cocaine, tropinone, tropine, littorine and cuscohygrine) have a strong
biological activity, especially as neurotransmitters.

Tropane Ring System

5.2.5 QUINOLINE ALKALOIDS
The alkaloids containing principally the ‘quinoline’ nucleus comprise a series of
alkaloids obtained exclusively from the Cinchona bark. These alkaloids possess
the basic skeleton of 9’-rubanol that is derived from the parent compound
known as Ruban. The major members of this particular group are, namely:
quinine, quinidine, cinchonine and cinchonidine.
FORENSIC SCIENCE PAPER No.9: Drugs of Abuse
MODULE No.33: Alkaloids
Quinoline Ring System

5.2.6 ISOQUINOLINE ALKALOIDS
The Isoquinoline alkaloids are a huge class of medicinally active alkaloids whose
properties are variable. Their properties include being anti-spasmodic, anti-microbial,
anti-tumour, antifungal, anti-inflammatory, antiviral, amoebicidal and anti-oxidant and
can also act as enzyme inhibitors. This class notably includes morphine and codeine.
They are derived from the amino acids phenylalanine or tyrosine. They are formed from a
precursor of 3, 4- dihydroxytyramine (dopamine) linked to an aldehyde or ketone.

Isoquinoline Ring System

Examples: Opium alkaloids (Papaverine, Narcotine, Narceine), Pancratistatin,
Sanguinarine, Hydrastine, Berberine, Emetine, Berbamine, Oxyacanthine.

5.2.7 INDOLE ALKALOIDS
This structural group of indole alkaloids contains Indole ring. E.g., tryptamine, serotonin,
Ergometrine, psilocin and psilocybin. Indole alkaloids form a very important group from
the perspective of their application.
FORENSIC SCIENCE PAPER No.9: Drugs of Abuse
MODULE No.33: Alkaloids
Indole Ring System
Examples,
Tryptamines : Serotonin, Bufotenine, Psilocybin
Ergolines : Ergine, Ergotamine, Lysergic Acid
Beta Carbolines : Harmine, Harmaline, Tetra Hydro Harmine
Yohimbans : Reserpine, Yohimbine
Vinca alkaloids : Vinblastine, Vincristine
Kratom alkaloids : Mitragynine, 7- Hydroxy Mitragynine
Tabernanthe iboga : Ibogaine, Voacangine, Coronaridine
Strychnos nux-vomica : Strychnine, Brucine

5.2.8 IMIDAZOLE ALKALOIDS
Imidazole alkaloids contain an imidazole ring structure in them. This group of alkaloids is
an exception in the transformation process of structures, because the imidazole nucleus is
already made at the stage of the precursor. Alkaloids from this group include, for
example, Dolichotheline, Pilocarpine and Pilosine.

Imidazole Ring System

FORENSIC SCIENCE PAPER No.9: Drugs of Abuse
MODULE No.33: Alkaloids