1. ALKALOIDS

2. Alkaloid
Alkaloid: Difficult to define No definitive difference between an alkaloid and naturally occurring complex amines.
Alkaloids:
Plant derived, are alkali and contain at least one Nitrogen atom. They also normally have a significant physiological action on humans and animals.
TRUE ALKALOIDS
The basic unit in the biogenesis of the true alkaloids are AMINO ACIDS. The non-nitrogen containing rings or side chains are derived from TERPENE units and / or ACETATE, while METHIONINE is responsible for the addition of methyl groups to nitrogen atoms.
Alkaloids are highly reactive substances with biological activity in low doses.

3. WHAT IS AN ALKALOID ?
Naturally-occurring compounds that contain nitrogen
Many have heterocyclic rings as a part of their structure
They are found mostly in plants
Many are physiologically active (often spectacularly)
Many are used by native peoples for religious or medicinal
purposes.
Many are basic (“alkaline”, due to an unshared pair on N)
Those nitrogen compounds that are found in all organisms
(i.e., amino acids, nucleic acids, etc.) are not considered
alkaloids.
Alkaloids are “secondary metabolites”, they are not
involved in primary metabolism.

4. Alkaloid Description
Contains nitrogen - usually derived from an amino acid.
Bitter tasting, generally white solids (exception - nicotine is a brown liquid).
They give a precipitate with heavy metal iodides. Except Caffeine.
Alkaloids are basic - they form water soluble salts.
In plants, they may exist in the free state, as salts or as N- oxides. Occur in a limited number of plants.

6. Alkaloids - Examples All contain at least one nitrogen atom
Names often end in “ine”, Large complex structures

7. Classification of Alkaloids
Biogenetic.
Based on the biogenetic pathway that form the alkaloids.
Botanical Source.
According to the plant source of alkaloids.
Type of Amines.
Primary, Secondary, Tertiary alkaloids.
Basic Chemical Skeleton

8. Pyridine and piperidine e.g. lobeline, nicotine
Phenylalkylamines:
e.g. Ephedrine
Pyridine and piperidine
e.g. lobeline, nicotine
Tropane
e.g. Atropine.

9. Quinoline
e.g.quinine and quinidine
Isoquinoline
e.g. papaverine
Phenantheren
e.g. Morphine

10. Indole
e.g.ergometrine
Imidazole
e.g. pilocarpine
Purine
e.g. caffeine

11. Steroidal
e.g. Solanum and Veratrum alkaloids
Terpenoid
e.g. Taxol

12. MORPHINE - A TYPICAL ALKALOID
basic due to the
unshared pair
contains nitrogen ..
Plant source.
Most alkaloids
are found in
plants.
heterocyclic ring
This was the first
alkaloid discovered
(1804, Serturner).
Found only in the Opium Poppy - papaver somniferum
….. not ubiquitous.

13. HOW ARE ALKALOIDS CLASSIFIED ?
Common classification schemes use either:
The heterocyclic ring systems found as a
part of the compound’s structure
The plant or plant family where they originate*
* The majority of alkaloids (>90%) are found in plants -
therefore, we will speak mostly about plants and their
biochemistry.

14. HETEROCYCLIC RING SYSTEMS
LEARN THESE RINGS (plus the ones on the next page)
I will add a few more,
but at a later date.
short quiz (1-week) = M, October 8

15. HETEROCYCLIC RING SYSTEMS
(cont)
LEARN THESE ALSO
short quiz (~1-week) = M, October 8

16. Some Examples of Classification
BY RING TYPE

17. Some Examples of Classification
BY PLANT FAMILY :
“Amaryllis” Alkaloids
belladine
lycorine
The other three
are biochemically
derived from
belladine.
galanthamine
tazettine
daffodils
narcissus
lillies
etc
These alkaloids are found in Amaryllidaceae

18. Some Examples of Classification
BY PLANT OF ORIGIN
“Cinchona” Alkaloids
quinine
“Opium” Alkaloids
morphine

19. Common plant-derived drugs
Morphine: isolated from Papaver somniferum
Narcotic Analgesic

20. Common plant-derived drugs
Quinine: isolated from Cinchona officialis. 
Antimalarial

21. Common plant-derived drugs
Vinblastine: isolated from Cantharanthus roseus
Anticancer

22. Common plant-derived drugs
Atropine: isolated from Atropa Belladonna
Anticholenergic agents

23. Common plant-derived drugs
Digitoxin: from Digitalis purpurea (foxglove)
Cardiac glycoside: CHF

24. Common plant-derived drugs
Taxol: isolated from Taxus (Pacific Yew)
Anti-cancer

25. Common plant-derived drugs
Etoposide: isolated from Podophyllum Peltatum
Anti-cancer

26. Common plant-derived drugs
Colchicine: isolated from Colchicum Autamnale
Gout

27. Common plant-derived drugs
Acetyl Salicylic Acid: isolated from Salix Alba
Analgesic

28. Natural Products Chemistry
Primary metabolites 1. Direct function in primary biochemical pathways
 are essential for life (G-3P, R-5P)
Secondary metabolites 1. Synthesized directly from primary metabolites 2. NOT involved in the primary life-sustaining processes
 important in proper biochemistry

29. Secondary Metabolites
Primary classes
Terpenes – Cholesterol synthesis
Phenylpropanoids – Fatty acids
Polyketides – Fatty acids
Steroids – Progesterone, etc.
Glycosides – Protein glycolosys, etc.
Alkaloids – Amine containing moiety

30. Tests for Alkaloids
Most alkaloids are precipitated from neutral or slightly acidic solution by
Mayer's reagent (potassiomercuric iodide solution)  Cream coloured precipitate.
Dragendorff's reagent (solution of potassium bismuth iodide) orange coloured precipitate.
Wagner’s reagent (iodine in potassium iodide)  red-brown precipitate
Hagers reagent (picric acid)  yellow precipitate
Caffeine does precipitate

31. Occurrence Distribution & of Alkaloids
Occur in bacteria and rarely in fungi.
Some alkaloids occur in several genera from different species, but most occur in closely related species.
Some occur in certain families
All alkaloids of one plant will have a common biogenenetic origin.

32. The N2 atom can either be 1º, 2º, 3º or 4º (quaternary).
Chemistry of Alkaloids
The N2 atom can either be 1º, 2º, 3º or 4º (quaternary).
This N2 feature affects the alkaloid derivatives which can be prepared and the isolation procedures

33. Physical & chemical properties
The basicity of alkaloids depends on the availability of the lone pair of e- on the N2 atoms:
Because some alkaloids have a carbonyl group on the amide, they can also be neutral (colchicine & piperine).
Basic characteristic renders complex alkaloids unstable, so that in solution they are sensitive to heat, light & oxygen.
Basic character of alkaloids also allows them to form salts with mineral acids (such as hydrochlorides, nitrates and sulphates) or inorganic acids (tartrates, sulfamates).
Solid salts can be conserved well and are a common commercial form of alkaloids.

34. MW: 100 – 900 , they are whit crystals. In rare cases they are coloured.
Most bases which do not contain O2 are liquid at room temperature
All active except Purins
Soluble in concentrated hydroalcoholic solutions
They give a precipitate with heavy metal iodides. Caffeine, a purine derivative, does not precipitate like most alkaloids.

35. Naming of Alkaloids Numerous methods can be used to name alkaloids
Generic plant name – atropine from Atropa belladonna
Specific name of the plant – cocaine from Erythroxylum coca.
Common name of the herb – ergotamine from ergot (rye)
Physiological action of the plant – emetine producing emesis
Other – e.g. morphine derived from ancient Greek mythology – Morpheus – god of dreams

36. Extraction of Alkaloids
Extraction is based on the basicity of alkaloids ( they normally occur in plants as salts).
Herbs often contain other materials which interfere with extraction by forming emulsions.( waxes, terpenes, pigments and other lipophilic substances) avoided by defatting
Extraction method normally depends on the raw material, the purpose of extraction & the scale on which is to be performed.
For research purposes: chromatography allows for quick and reliable results.
TLC plate