introduction, general structure elucidation, biological activity.

1. Alkaloids
PRESENTED BY: ROHIT PAL
M PHARMA FIRST YEAR
PHARMACEUTICAL CHEMISTRY

2. Content
• General introduction
• Classification
• Isolation and purification
• Molecular modification
• Biological activity

3. General introduction
• The term “alkaloid” (alkali-like) is defined as
physiologically active basic compounds of plant
origin, in which at least one nitrogen atoms
forms part of a cyclic system.
• The term alkaloid was coined by W. Meissner, a
German Pharmacist in 1819.

5. Classification:
• True (Typical) alkaloids that are derived from amino acids
and have nitrogen in a heterocyclic ring. e.g Atropine
• Protoalkaloids that are derived from amino acids and do
not have nitrogen in a heterocyclic ring. e.g Ephedrine
• Pseudo alkaloids that are not derived from amino acids
but have nitrogen in a heterocyclic ring. e.g Caffeine
• False alkaloids are non alkaloids give false positive
reaction with alkaloidal reagents.

6. Classification of alkaloids
• 1. Chemical classification of alkaloids
• 2. Taxonomical classification of alkaloids
• 3. Pharmacological classification of alkaloids
• 4. Biosynthetic classification of alkaloids

7. Biosynthetic classification of alkaloids
(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.

8. Chemical classification of alkaloids
1) Phenylethylamine : Ephedrine
2) Pyrrolidine: Hygrine,
stachydrine
3) Pyridine or piperidine:
Lobeline, nicotine, piperine,
conine, trigonelline
4) Pyridine-pyrrolidine: Nicotine
5) Tropane: Cocaine, atropine,
hyoschyamine, hyoscine
6) Quinoline: Quinine, quinidine,
cinchonine, cinchonidine

9. 7) Isoquinoline: Morphine,
codeine, papaverine, norcotine,
tubocurarine, emetine
8) Phenanthrene: Morphine,
codeine, thebaine
9) Indole: Reserpine, ergometrine,
strychnine, Yohimbine,
serpentine, physostigmine
10) Tropolone: Colchicine
11) Imidazole: Pilocarpine,
pilosine
12) Steroidal: Conessine,
solanidine
13) Purine: Caffeine, theobromine
14) Terpene: Aconitine

10. Pharmacological classification of
alkaloids
• 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.

11. 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.

12. Taxonomic Classification
• This particular classification essentially deals with
the ‘Taxon’ i.e., the taxonomic category. The
most common taxa are the genus, subgenus,
species, subspecies, and variety. Therefore, the
taxonomic classification encompasses the plethora
of alkaloids exclusively based on their respective
distribution in a variety of Plant
Families, sometimes also referred to
as the ‘Natural order’. A few typical examples of
plant families and the various species
associated with them are stated below, namely:

13. • (i) Cannabinaceous Alkaloids: e.g., Cannabis
sativa Linn., (Hemp, Marijuana).
• (ii) Rubiaceous Alkaloids: e.g., Cinchona
Sp. (Quinine); Mitragyna speciosa Korth (Katum,
Kratum, Kutum); Pausinystalia johimbe (K. Schum)
(Yohimbe).
• (iii) Solanaceous Alkaloids: e.g., Atropa
belladona L., (Deadly Nightshade,
Belladona); Capsicum annuum L., (Sweet Peppers,
Paprika); Datura candida (Pers.) Saff. (Borrachero,
Floripondio) etc.
• Invariably, they are grouped together according to the
name of the genus wherein they belong to, such
as: coca, cinchona, ephedra.

15. Isolation of alkaloids
• The resulting crude alkaloid mixture is separated into individual alkaloids by means of fractional
Crystallization, fractional precipitation, column chromatography, partition chromatography, Gas
chromatography or counter current extraction.

17. Molecular modification
• Molecular modification is chemical alteration of a known and
previously characterized lead compound for the purpose of
enhancing its usefulness as a drug.
• Medicinal chemistry is a chemistry-based discipline, involving
aspects of biological, medical and pharmaceutical sciences.
• It is concerned with the
 invention,
 discovery,
 design,
 identification and
 preparation of biologically active compounds,
 the study of their metabolism,
 the interpretation of their mode of action at the molecular level and
 The construction of structure-activity relationships (SARs).

18. Molecular modification of opioid
alkaloids
• The term opiate refers to compounds structurally
related to products found in opium, a word
derived from opos, the Greek word for “juice,”
natural opiates being derived from the resin of
the opium poppy, Papaver somniferum.
• Opiates include the natural plant alkaloids, such
as morphine, codeine, thebaine, and many
semisynthetic derivatives.

19. Morphine as lead
• Biological activity of opioids
• Depends on

22. SAR - Methyl group on nitrogen
• Nitrogen is essential for binding
• The pure opioid antagonist drugs
naloxone, naltrexone, and nalmefene are
morphine derivatives with bulkier
substituents at the N17 position.
• These agents have a relatively high
affinity for μ-opioid binding
sites. They have lower affinity for the other
receptors but
can also reverse agonists at δ and κ sites.

23. Summary of SAR
• Of course, thousands of compounds related to the morphine structure have
been prepared and many without activity, and no compound has been found to
halt the terrible addictive morphine properties.
• When Used correctly, the morphine family is an important class of analgesics,
and their study represents an important contribution to the understanding of
medicinal activity.

30. 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.

31. 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.