- Alkaloids are nitrogen-containing compounds found in about 20% of vascular plants that are usually basic. There are over 40,000 alkaloid compounds described. - Many alkaloids have biological activity and pharmacological properties. Examples include morphine, vincristine, cocaine, nicotine, and caffeine. - Alkaloids are classified into three main types: proper/true alkaloids derived from amino acids, proto-alkaloids with nitrogen outside the ring system, and pseudoalkaloids not derived from amino acids.

1. Alkaloids
Found in ~20% of vascular plants.
Compounds usually basic (alkaline).
~40,000 compounds currently described.
Structurally the most diverse class of secondary metabolites.
N
H
H
(+)-coniine
(Conium maculatum)
poison hemlock
HO
H
HO
O
H
O
O
NH
N
batrachotoxin
(Phyllobates aurotaenia)
Columbian arrow frog
LD50 (mice) = 2mcg/kg sc

2. Many natural product alkaloids are of biological interest
• Morphine (painkiller)
• Vincristine (anticancer agent)
• Cocaine (anaesthetic, drug of abuse)
• Nicotine (tobacco, poison)
• Caffeine (stimulant)
Relatively straightforward to isolate.
Of intense interest to organic chemists for the challenge of
structural elucidation and total synthesis.
• Devise new synthetic methodologies
Alkaloids - Definitions
First definition (1817)
• Basic compounds
• Contain N (nitrogen) in molecule
• Can form salts with acids
• Occur in plants
• Pharmacologically active
1963 – Definition based on chemotaxonomy. Alkaloids should be
divided into 3 subgroups
• Proper alkaloids
• Proto alkaloids
• Pseudo alkaloids

3. Proper Alkaloids
Also known as true alkaloids.
Basic.
Nitrogen part of a heterocyclic ring system.
Chemically complex.
Derived biosynthetically from amino acids, especially the cyclic
amino acids:
• Phe, Tyr, Try, His
Many physiologically active.
Have limited distributions in the plant kingdom.
N
N
O
O
H H
H
H
H
N
H
COOH
NH2
L-tryptophan
(−)-strychnine
(Strychnos nux vomica)
(–)-strychnine – from the dried seeds of Strychnos vux vomica.
Small tree found from India to Northern Australia. Fruit is a large
berry with a hard coat and pulpy interior containing 3-5 fleshy grey
seeds – contain ~1.2% strychnine. 60mg can kill an adult.

4. Proto Alkaloids
Physiologically active.
Nitrogen atom is outside the ring system.
COOH
NH2
L-Phenylalanine
OH
NHCH3
(−)-ephedrine
sympathomimetic amine
(Ephedra sp.)
O
OMe
H
NH
O
colchicine
(Colchicum autumnale)
used in the tx of gout
cycloheptatrienone
ring

5. Pseudoalkaloids
Nitrogen containing (physiologically active) compounds not derived
from amino acids.
The purine ring is gradually elaborated by piecing together small
components from primary metabolism.
HN
N N
N
O
O
OH
HO
PO
inosine monophosphate
(IMP)
N
N N
H
N
O
O
theophylline
HN
N N
N
O
O
theobromine
N
N N
N
O
O
caffeine
N
N N
H
N
formate
formate
L-Gln
L-Gln
L-asp
CO2
Gly
purine alkaloids from Coffea species
(C. arabica, C. canephora, C. liberica, etc)

6. Alkaloid Nomenclature
N
O
(−)-hygrine
(Erythroxylum coca)
PYRROLIDINE
N
O
O
OH
( )-hyoscyamine (atropine)
(Atropa belladonna)
Deadly nightshade
TROPANE
NORTROPANE
HN
epibatidine
(Epipedobates tricolor)
Ecuadorian poison frog
200-500x potent then morphine
N
Cl
N
O
PIPERIDINE
N-methylpelletierine
N
O
pseudopelletierine
(Punica granatum)
pomegranate bark
possesses activity against intestinal tapeworms

7. N
OH
O
lobeline
(Lobelia inflata)
antiasthmatic
PIPERIDINE
PYRROLIZIDINE
N
pyrrolizidine
N
H
HO OH
retronecine
N
O
O
O
HO OH
O H
riddelliine
retronecine
riddellic acid
Senecio sp
(S. vulgaris) groundsel
(S. jacobaea) ragwort
PYRROLIZIDINE

8. (−)-lupinine
(Lupinus luteus)
yellow lupin
QUINOLIZIDINE
N
quinolizidine
N
H
OH
N
N
H
H
(−)-sparteine
(Cytisus scoparius)
Scotch broom
PYRIDINE
nicotine
(Nicotiana tabacum)
tobacco
N
N
H
anabasine
N
H
N
H
INDOLIZIDINE
indolizidine
castanospermine
(Castanospermum australe)
Moreton Bay chestnut
N
N
OH
H
OH
HO
HO

9. PYRROLOINDOLE
physostigmine
(Physostigma venenosum)
Calabar beans (Nigeria)
Cholinesterase inhibitor
N
H
NH
pyrroloindole
N
N
O
O
MeHN
H
PHENETHYLAMINE
O
NH2
(−)-cathinone
(Catha edulis)
khat
CNS stimulant
QUINOLINE PURINE
purine
quinoline
N
N
MeO
N
H
H
H
OH
(−)-quinine
(Cinchona sp)
antimalarial
N
N N
H
N
caffeine
N
N N
N
O
O

10. IMIDAZOLE
N
N O
O
pilocarpine
(Pilocarpus jaborandi)
cholinergic for glaucoma
β-CARBOLINE
N
H
N
β-carboline
N
H
N
harmine
(Peganum harmala)
Syrian rue
MeO
SIMPLE INDOLE
N
H
NMe2
OP
psilocybin
(Psilocybe mexicana)
magic mushrooms
ACRIDINE
rutacridone
(Ruta graveolens)
Garden rue
N
acridine
N O
O OH

11. QUINAZOLINE
quinazoline
N
N
peganine
(Peganum harmala)
Syrian rue
N
N
OH
PYRROLOQUINOLINE
pyrroloquinoline camptothecin
(Camptotheca acuminata)
Chinese tree
topoisomerase I inhibitor
N
N
N
N
O
O
O
OH
STEROIDAL ALKALOIDS
HO
H
H
H
cholestrol
O
H
N
H
H
H
H
H
H
HO
tomatidine
(Lycopersicon esculente)
tomato
squalamine
(Squalus acanthias)
dogfish shark
antimicrobial
H
N
H H
OH
H H
OSO3H
N
H
H2N

12. BENZYLTETRAHYDROISOQUINOLINE
benzyltetrahydroisoquinoline (R)-reticuline
NH N
MeO
HO
HO
MeO
H
TETRAHYDROISOQUINOLINE
tetrahydroisoquinoline
anhalamine
(Lophophora williamsii)
Peyote
NH NH
OH
MeO
MeO
O
MeO
MeO
H
N
thebaine
O
RO
HO
H
N
R = H morphine
R = Me codeine
H
(Papaver somniferum)
Opium poppy
analgesic, antitussive
MODIFIED BENZYLTETRAHYDROISOQUINOLINE
NH
morphinan

13. BISBENZYLTETRAHYDROISOQUINOLINE
N
O
N
O
OH
OMe
OH
MeO
H
H
(+)-tubocurarine
(Chondrodendron tomentosum)
arrow poison curare