Natural Products

1
Natural Products

• Approximately 25 of Rx drugs are plant natural
  products or are semi-synthetics
• Approximately 15 of all Rx drugs are based on
  compounds initially isolated from plants
• Greater than 50 of the OTC products on the
  marketcontain at least one component of plant
  origin

2
Common plant-derived drugs

• Morphine isolated from Papaver somniferum
• Narcotic Analgesic

3
Common plant-derived drugs

• Quinine isolated from Cinchona officialis. 
• Antimalarial

4
Common plant-derived drugs

• Vinblastine isolated from Cantharanthus roseus
• Anticancer

5
Common plant-derived drugs

• Atropine isolated from Atropa Belladonna
• Anticholenergic agents

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Common plant-derived drugs

• Digitoxin from Digitalis purpurea (foxglove)
• Cardiac glycoside CHF

7
Common plant-derived drugs

• Taxol isolated from Taxus (Pacific Yew)
• Anti-cancer

8
Common plant-derived drugs

• Etoposide isolated from Podophyllum Peltatum
• Anti-cancer

9
Common plant-derived drugs

• Colchicine isolated from Colchicum Autamnale
• Gout

10
Common plant-derived drugs

• Acetyl Salicylic Acid isolated from Salix Alba
• Analgesic

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Natural Products Chemistry

• Primary metabolites1. Direct function in
  primary biochemical pathways
• ? are essential for life (G-3P, R-5P)
• Secondary metabolites1. Synthesized directly
  from primary metabolites2. NOT involved in the
  primary life-sustaining processes
• ? important in proper biochemistry

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Secondary Metabolites

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

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Terpenes

• Common examples and plant parts
• Cinnamon in bark
• Peppermint in hairs on leaves
• Lemon - in the rind
• Rose in the petals
• Ginger in the rhizome

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Terpene Synthesis

• Synthesized by the mevalonic acid pathway

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Terpene Synthesis cont.
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IPP and DMAP Biological Isoprene Building
blocks
C10 Geranyl isoprenoid synthesis
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IPP and GPP Biological Isoprene Building
blocks
C15 Farnesyl isoprenoid synthesis
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FPP Biological Isoprene Building blocks
C30 Squalene synthesis
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Mevalonic Acid Pathway Produces Cholesterol
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Mevalonic Acid Pathway Produces Cholesterol
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Terpene Classes

• C5 Hemiterpenes
• C10 Monoterpenes
• C15 Sesquiterpenes
• C20 Diterpenes
• C25 Sesterterpenes
• C30 Triterpenes
• C40 Carotenoids

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Examples of Terpenes
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Phenylpropanoids

• Occur as mixtures with Terpenes in essential oils
  isolated from plants
• Flavonoids water soluble plant pigments
• Anthocyanidins improve microcirculation
  nightvision
• Coumarins - Anticoagulants
• Lignans Anti-cancer drugs
• Tannins in green tea, red raspberry witch
  hazel
• Interact with Theophylline/Aminophylline
  (bronchodilators)

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Phenylpropanoid synthesis
Shikimic Acid Pathway
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Shikimic Acid Pathway
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Shikimic Acid Pathway
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Shikimic Acid Pathway
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Shikimic Acid Pathway
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Shikimic Acid Natural Products
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Shikimic Acid Flavones
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Shikimic Acid Coumarin Products
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Shikimic Acid Lignins
A synthetic Lignan
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Shikimic Acid Tanins
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Polyketide Biosynthesis
Highly modified via cyclization, reduction and
oxidation
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Glycosides Aglycone plus a Sugar
An Aglycone is the non-sugar compound that
remains after replacement of a glycosyl group in
a glycoside
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Alkaloids

• All contain at least one nitrogen atom
• Names often end in ine, Large complex
  structures

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Alkaloids - Examples

• All contain at least one nitrogen atom
• Names often end in ine, Large complex
  structures

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What should I remember?

• Many drugs are derived from plants
• Primary v. Secondary metabolites
• Key secondary metabolites
• Terpenes
• Phenylpropanoids
• Polyketides
• Steroids
• Glycosides
• Alkaloids
• Reactions that they undergo
• Mevalonic acid pathway
• Shikimic acid pathway
• Products that are formed
• Endogenous (i.e. steroid hormones, etc.)
• Exogenous (drugs)