NATURAL PRODUCTS

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NATURAL PRODUCTS
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Professor Donald Pavia
MWF 1200 noon Chemistry Building (CB 485)
TEXTS

• Manfred Hesse, Alkaloids - Natures Curse or
  Blessing?,
• Wiley-VCH (2002). (on reserve)

• R.E. Schultes, A. Hofmann and C. Ratsch,
• Plants of the Gods, 2nd ed., Healing Arts Press
  (2001).
• (bookstore)

• D. Pavia, Chemistry of Natural Products - Notes,
  
• WWU Chemistry Department (online)

See web site for reserve book list
GRADING
Two Hour Exams, occasional quizzes, Problem
sets, Poster Presentation
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NATURAL PRODUCTS

• Compounds that occur naturally in plants and
  animals

• Ubiquitous compounds are usually not classified
  as
• natural products.

Ubiquitous occurs everywhere in nature,
universal
excludes amino acids, nucleic acids, all
compounds found in major metabolic pathways.

• Natural products are unique to only one species
  or family
• of organisms.

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SOME CLASSES OF NATURAL PRODUCTS

• Acetogenins
• Terpenes
• Steroids
• ALKALOIDS
• Pigments
• Carbohydrates
• Fats and Lipids

This quarter we will focus our attention on
alkaloids, although some attention will be paid
to the other classes as well, especially
acetogenins, terpenes and steroids.
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ALKALOIDS
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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.

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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.
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CLASSIFICATION SCHEMES FOR ALKALOIDS
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HOW ARE ALKALOIDS CLASSIFIED ?
Common classification schemes use either

• The heterocyclic ring systems found as a
• part of the compounds structure

• The plant or plant family where they originate

The majority of alkaloids (gt90) are found in
plants - therefore, we will speak mostly
about plants and their biochemistry.
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HETEROCYCLIC RING SYSTEMS
LEARN THESE RINGS (plus the ones on the next
page)
short quiz (1-week) M, October 8
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HETEROCYCLIC RING SYSTEMS
(cont)
LEARN THESE ALSO
short quiz (1-week) M, October 8
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Some Examples of Classification
BY RING TYPE
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Some Examples of Classification
BY PLANT FAMILY
Amaryllis Alkaloids
belladine
lycorine
The other three are biochemically derived
from belladine.
galanthamine
tazettine
These alkaloids are found in Amaryllidaceae
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Some Examples of Classification
BY PLANT OF ORIGIN
Cinchona Alkaloids
quinine
Opium Alkaloids
morphine
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ASSIGNMENTS
FAMILIARIZE YOURSELF WITH THE BROAD SCOPE AND
CLASSIFICATION OF ALKALOIDS
READ
Manfred Hesse, Alkaloids -Natures Curse or
Blessing, Wiley-VCH, Weinheim, De (2002).
Chapter 1, Introduction, pages 1-8 Chapter
2, Classification of Alkaloids, pages
11-92. Chapter 9, Biological Significance of
Alkaoids, pages 283-310
This is obviously too much material to memorize
at this time. Read to get an idea of the scope
and classification patterns of the alkaloids, not
to memorize structures.
DUE Friday, October 5
The Buff Problem
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LONG TERM ASSIGNMENT
Become proficient with these computer programs
ChemDraw or Isis Draw
ChemDraw is the standard for chemists and is used
to submit publication material to journals. It is
available in the chemistry computer
classroom. WWU has a site license. Students who
have a WWU email address may download a copy free
from scistore.cambridgesoft.com/sitelicense_galle
ry.cfm Select WWU from the list and follow
directions.
Isis Draw is also available as freeware
(www.mdli.com). It is not as powerful as
ChemDraw but is free and you can download it and
use it at home. (smaller program)
Microsoft Powerpoint
Powerpoint is also available in the chemistry
computer classroom. You will need it at the end
of the quarter to prepare your project poster.
There is no freeware alternative.
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PURPOSE OR FUNCTION OF ALKALOIDS
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THE PURPOSE OF ALKALOIDS IN PLANTS (?)
The spectacular pharmacological properties of
many of the alkaloids keeps asking about their
purpose in plants.
Many ideas have been advanced
Defense Mechanisms Insect Repellants
Herbivore Attractants
Nitrogen Storage
Growth Regulation
Insect Attractants
Vestiges of Old Metabolic Experiments
Anti-fungals
Metal ion transport (chelates)
Competitive Herbicides
What seems most likely is that there are many
reasons why plants elaborate alkaloids, and in
many cases the purpose of the alkaloid may be
unique to a given plant.
Read this (already assigned) to find out more
Read Manfred Hesse, Alkaloids -Natures Curse or
Blessing, Wiley-VCH, Weinheim, De
(2002), Chapter 9, Biological
Significance of Alkaloids, pages 283-310.
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PRIMARY AND SECONDARY METABOLISM
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A TYPICAL PLANT
hn
Glycolysis
ENERGY
Photosynthesis
(daytime)
CO2
Respiration
H2O
(nighttime)
O2
N2
bacteria
N
TRACE METALS
NO2-/NO3-/NH4
Na, Ca, K, Mg Fe, Cu, Co, Mo
H2O
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PRIMARY METABOLISM
Primary metabolism comprises the chemical
processes that every plant must carry out every
day in order to survive and reproduce its line.
Photosynthesis Glycolysis Citric Acid
Cycle Synthesis of amino acids Transamination Synt
hesis of proteins and enzymes Synthesis of
coenzymes Synthesis of structural
materials Duplication of genetic
material Reproduction of cells (growth) Absorption
of nutrients
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SECONDARY METABOLISM
Secondary metabolism comprises the chemical
processes that are unique to a given plant, and
are not universal.
Secondary metabolism is the chemistry that leads
to the formation of a natural product.
Sometimes portions of this chemistry are common
to a number of different plants or plant
families, but the actual chemical produced
(natural product) is usually different in one
plant than in another.
Common chemical precursors can lead to different
results.
Secondary metabolites (in most cases) do not
appear to be necessary to the survival of the
plant, but they may give it a competitive
advantage.
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CO2 H2O
PRIMARY METABOLISM
hn
Photosynthesis
Glucose
Carbohydrates
SECONDARY METABOLISM
SECONDARY METABOLISM
GLYCOLYS IS
Building Blocks
Phenyl- propanoids
Fatty Acids Lipids
Amno Acids
Flavonoids
Proteins
synthesis
Alkaloids
Acetyl CoA
enzymes
Acetogenins Terpenes Steroids
regulation
Nucleic Acids
Citric Acid Cycle
reproduction
RNA DNA
CO2 H2O ATP
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Glucose (6 carbons)
photosynthesis
starch
n
glycolysis
erythrose- 4-phosphate
phosphoenol pyruvate (PEP) (3 carbons)
shikimic acid
anthanilic acid
acetyl- coenzymeA (2 carbons)
mevalonic acid
oxalo- acetate
lysine ornithine
phenylalanine tyrosine
energy (ATP) CO2 H2O
tryptophan
terpenes steroids carotenoids
NH3
nicotinic acid
aspartic acid
glutamic acid
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ASSIGNMENTS (repeat)
FAMILIARIZE YOURSELF WITH THE BROAD SCOPE AND
CLASSIFICATION OF ALKALOIDS
READ
Manfred Hesse, Alkaloids -Natures Curse or
Blessing, Wiley-VCH, Weinheim, De (2002).
Chapter 1, Introduction, pages 1-8 Chapter
2, Classification of Alkaloids, pages
11-92. Chapter 9, Biological Significance of
Alkaoids, pages 283-310
This is obviously too much material to memorize
at this time. Read to get an idea of the scope
and classification patterns of the alkaloids, not
to memorize structures.
DUE Friday, October 5
The Buff Problem