ALKALOIDS
As to the nature of the basic chemical
 Are organic nitrogenous compounds processing
 Basic properties (owing to the presence of
amino N)
 Marked physiological activities
 In majority of instances, they are medicinally
important substances of the plants from which
they are derived
 Some are extremely poisonous
 In addition to their basic nitrogen moiety,
alkaloids usually contain one or more chemically
functional groups
Example:
 Cocaine contains two ester functions
 Quinine contains both secondary alcohol
and aromatic methoxy functions
 Ergonovine contains 2 substituted amide
function
 Solanine and tomatine usually occur as
OCCURENCE (LIMITED DISTRIBUTION IN NATURE):
 Plants have been a rich source of alkaloids but
some are found in animals, fungi and bacteria
 Practically all have been synthesized
In plants:
 Few from cryptograms (flowerless plants)
Example: Taxaceae
 Majority from Phanerograms (flowering plants)
most from dicotyledons as Fabaceae,
Papaveraceae, Ranunculaceae, Rubiaceae,
Solanaceae and Berberidaceae are out-standing
alakaloid-yielding plants
 A few in monocotyledons as Amaryllidaceae
and Liliaceae
 Alkaloids occur in various parts of the plants
 Seeds (physostigma, areca)
 Fruits (opium)
 Underground stem (sanguinaria)
 Roots (belladonna)
 Rhizomes and roots ( ipecac and hydrastis)
 Bark ( cinchona)
 Also found in fungi—ERGOT
BASIS OF CLASSIFICATION:
1. As to source
Example: Opium alkaloids, Ergot alkaloids,
Vinca alkaloids, Cinchona alkaloids
2. As to pharmacologic activity
Example: Cardiac alkaloids, Cathartic
alkaloids
3.
structure
Example: Pyridine-piperidine, Tropane,
Quinidine
PROPERTIES:
1. In addition to C and H they all contain N and
generally also O
-the N is contained in whole or in part,
in the heteronucleus, confers the alkali-
property to alkaloids
-the N may exist as:
 Primary amine-RNH2
 Secondary amine- R2NH
 Tertiary amine-R3N
2. Most of the non-volatile alkaloids are solid,
the volatile ones are mainly liquid and these
often contain no oxygen
3. They are mainly crystallisable, through a
few are amorphous. Some such as coniine,
nicotine and sparteine are liquid(the free
alkaloid) under ordinary conditions
4. They are generally white though berberine
is yellow and sanguinarine itself colorless
yields red salts
5. They are ether insoluble/ sparingly soluble
in water (with few exceptions, such as
colchicines) but soluble in alcohol, CHCl3
some in ether and a few in petroleum ether.
Their salts behave conversely in matters of
solubility
6. Most of them are physiologically active,
some being extremely poisonous. In
majority of instances they are medicinally
important substances of the plants from
which they are derived
7. They unite with acids to form substituted
NH +4 salts. The stability of these salts
toward hydrolysis varies with the basic
strength of the alkaloid and the nature of
the acid used. The alkaloids are freed from
their salts by the addition of alkali
8. They are precipitated by one or more of the
following reagents, with some they form
definite chemical compounds which are
used for their identification
CLASSIFICATION (BASED ON THE BASIC CHEMICAL 4. Isoquinoline
STRUCTURE FROM WHICH THEY ARE DERIVED): Example: Hydrastine, Tubocurarine,
1. Pyridine-piperidine Emetine and Opium Alkaloids
Example: Arecoline, Lobeline, Nicotine Drugs:
Drugs:  Ipecac
 Tobacco  Hydrastis/Golden seal
 Areca  Sanguinaria
 Lobelia  Curare/ South American Arrow
Poison
Biosynthesis: Trier proposed that nicotine  Opium/ Gum Opium
was biosynthesized from nicotinic acid and  Morphine
proline  Codeine/Methylmorphine
Tracer studies have shown that HCl
ornithine is incorporated into nicotine by  Heroin/ Diacetylmorphine
tobacco plants  Apomorphine
 Papaverine
2. Tropane  Hydromorphone HCl/
Example: Atropine, Hyoscyamine, Hyoscine Dihydromorphinone HCl
(Scopolamine)  Hydrocodone bitartrate/
Drugs: Dihydrocodeinone
 Belladonna bitartrate
 Hyoscyamus/ Henbane  Noscopine/ Narcotine
 Egyptian Henbane Biosynthesis: These compounds results from the
 Stramonium/Jimson weed/ condensation of a phenylethylamine derivative
Jamestown weed with a phenyl acetaldehyde derivative
 Other solanaceous drugs: Both of these moieties are
 Withania derived from phenylalanine or tyrosine
 Duboisia
 Pituri/ Australian tobacco 5. Indole alkaloids
 Mandragora/ European Example: Ecgonovine, Reserpine,
mandrake Strychnine, Yohimbine
 Coca/ Coca leaves Drugs:
Biosynthesis: Phenylalanine is the precursor  Rauwolfia serpentine
of tropic acid  Catharanthus/ Vinca
Esterification of tropic acid with  Nux Vomica
tropine produces hyoscyamine  Physostigma/ Calabar bean/ Ordeal
bean
3. Quinoline  Ergot/ Rye ergot/ Secale Cornutum
Example: Cinchona Akaloids (quinine, Biosynthesis: Incorporation of a tryptamine
quinidine, cinchonine, cinchonidine) moiety into this type of alkaloid was
Drugs: established at fairly early stage in the study
 Cinchona/ Cinchona Bark/ Peruvian of alkaloid biosynthesis
Bark It is now established that the
Biosynthesis: studies indicate that quinine is nontryptophan portions of the molecules
metabolically derived from monoterpenoid- are derived from monoterpenoid precursors
tryptophan pathway that leads to the
corynanthe-type indole alkaloids
6. Imidazole NAMING OF ALKALOIDS:
Example: Pilocarpine 1. Based on the generic name
Drugs: Example: Atropine, Strychnine,
 Pilocarpus/ Jaborandi Theobromine
Biosynthesis: Formed from histidine or a 2. Based on the species name
metabolic equivalent but experimental Example: Belladonnine and Cocaine
confirmation of such biosynthetic origin is 3. Based on the common name
lacking Example: Mescaline and Colchicine
4. Based on the physiologic activity
7. Steroidal Example: Emetine
Example: Protoveratrine 5. Based on the discoverer
Drugs: Example: Pelletierine
 Veratrum viride/ American/ Green
Hellebore FUNCTIONS OF ALKALOIDS IN PLANTS:
 White Hellebore/ European 1. Poisonous substance protecting the plants
Hellebore from insects and herbivores
Biosynthesis: These are derived 2. End products of the plants detoxification
biosynthetically from six isoprene units and process/ reactions representing metabolic
could be classified as triterpenoids or locking up of compounds otherwise
steroids harmful to the plant
3. Regulatory growth factors
8. Alkaloidal amines 4. Preserve substance capable of supplying N
Example: Ephedrine and other elements necessity to the plant
Drugs: economy
 Ephedra/ Ma Huang
 Colchicum PHARMACOLOGIC ACTION OF ALKALOIDS VARIES
 Khat/ Abyssinian tea WIDELY:
 Peyote/ Mescal Buttons 1. Analgesics and narcotics
Biosynthesis: Are simple derivatives of (morphine, codeine)
phenylethylamine 2. Central stimulants (strychnine, brucine)
3. Mydriatics (atropine)
9. Purine bases 4. Miotics (physostigmine, pilocarpine)
Example: Caffeine, Theophylline, 5. Cause a rise in BP (ephedrine)
Theobromine 6. Decrease BP in hypertension (reserpine)
Drugs: -alkaloids are capable of extensive
 Kola/ Cola/ Kolanuts physiologic activity
 Coffee bean/ Coffee seed
 Guarana
 Mate/ Paraguay tea
 Thea/ Tea
 Theobroma
Biosynthesis: Serine, glycine, formaldehyde
and methanol as well as methionine are
active precursors