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Mevalonic Acid Pathway
• Many constituents are unsaturated hydrocarbons
• Ketons, alcohols, simple hydrocarbons are
formed
• Through acetate-mevalonate pathway synthesis
• Acyclic, monocyclic, bicyclic,…..
• Occur in a free form, as glycosides, esters of org.
acids and with proteins
• Meroterpenoids (=mixed terpenoids)
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Terpenes/Terpenoids
• Large structurally diverse family of natural products
>35,000
• Formed from C5 Isoprene units joined together
The fundamental building block for terpenes
• Joining of C5 units through Head to tail or Tail to tail
fashion
• Classification is based on the number of isoprene
units forming the carbon skeletons
• Stereoisomers, optical isomers
• Each member of a terpenoid subgroup is derived
from a single parent compound(i.e. Monoterpenes
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from geranyl-PP )
Mevalonic Acid and Methylerythritol
Phosphate Pathways
• Mevalonic acid (MVA) is an
intermediate for isoprene
units
• MVA is a product of acetate
metabolism (all living tissues
cytosol [cytoplasmic matrix])
• Methylerythritol phosphate
(MEP) is another
intermediate for isoprene
units (plants chloroplasts)
• MEP arises from
glyceraldehyde-3-phosphate
and pyruvic acid (Lacked in
animals and fungi)
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HO2C
6
2
OH
3
4
5
OH
Mevalonic acid (MVA)
OH
HO
1
2
3
4
OP
OH
2-Methyl-D-erythritol 4-phosphate
(MEP)
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Classification of Terpenes
•
Based on the number of Isoprene units in the compound Carbon
skeletons represented by (C5)n n=number of isoprene units
Classes of Terpenes:
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1) Hemiterpenes C5*
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2) Monoterpenes C10**
2
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3) Sesquiterpenes C15**
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C5 isoprene Unit Isoprene
4) Diterpenes C20
5) Sesterpenes C25
6) Triterpenes C30
7) Teteraterpenes C40
8) Polyterpenes >C40
*found together with mixed terpenoid substances; alkylating agents
**mainly volatile substances
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Synthesis of active isoprene units
through MVA
O
3
SCoA
acetyl-CoA
Claisen
Reaction
E
Aldol
Condensation
HO2C
O
OH
SCoA
3-hydroxy-3-methylglutaryl-CoA
(HMG-CoA)
E = HMG-CoA Synthase
IPP = Isopentyl Pyrophosphate
DMAPP= Dimethylallyl Pyrophosphate
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1
HO2C
OH
5
OH
3
2
4
Mevalonic acid
(MVA)
Phosphorylation
Decarboxylation
5
1
2
3
4
DMAPP
OPP
Steriospecific allylic
isomerization
1
2
3
IPP
4
OPP
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Terpenes Classes Corresponding to Parent Molecules/ Polymerization
Mevalonic acid
Methylerythritol phosphate
OPP
DMAPP
IPP
OPP
Hemiterpenes (C5)
Geraniol
Geranyl diphosphate
IPP
Monoterpenes (C10)
C10
OH
Farnesol
Farnesyl diphosphate
Sesquiterpenes (C15)
C15
IPP
OH
Geranylgeraniol
C20
Geranylgeranyl
diphosphate
Diterpenes (C20)
OH
IPP
Sesterpenes (C25)
C25
Squalene
C30
Triterpenes (C30)
Steroids (C18-C30)
Phytoene
C40
Tetraterpenes (C40)
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Volatile Oils
Large group of natural products of a
complex mixture of aromatic-smelling
volatile components containing either
phenylpropanes (shikimic acid-derived) or
terpenes (acetate-derived)
Can be classified according to the
biogenetic origin or based on the
functional groups: hydrocarbon v.o.,
alcohol v.o., aldehyde v.o., keton v.o.,….
Common properties of volatile oils
1.
2.
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Liquids at room temperature (exemptions!)
Colourless or slightly yellowish
Low solubility in H2O
Soluble in organic solvents
Optically active
High refractive index
Mostly lighter than H2O EXCEPT clove, cinnamon & sassafras
oils
8. Oxidized by O2 from air (resinification)
9. Light exposure oxidation (small, amber glass containers)
10. Do not stain filter paper (fixed oils do)
11. Evaporate at room temp.
12. Obtained by steam distillation (pharmaceutical use), water
distillation, expression (citrus oils), organic solv. extraction 8
Further properties of volatile oils
• Very complex, aromatic-smelling mixture of compounds
(phenylpropenes/ terpenoids) evaporating when exposed to air
at room temperature
• Synthesized in plants in specific organs (glandular hairs,
secretory ducts, oil cells)
• 30% plant families are rich in VO
• Apiaceae, Lamiaceae, Lauraceae, Myrtaceae & Rutaceae are
richest V.O. families
• Steam distillation is official method for V.O.-pharmaceutical
grade
• Economically valuable in pharmaceutical, food, cosmetic, paint
and textile industries
• GC-MS is the most suitable method for the identification of v.o.
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Uses of Volatile Oils
Insecticides
Industry
Cosmetic & Toiletries
Dental Preparations
Paint Industry
Volatile Oils
Textile Industry
Adhesives
(Glues & tapes)
Pharmaceutical
Industry
Tobacco Industry
Paper & Printing Industry
Food & Hygiene
Industry
Pharmaceutical uses of the volatile oils
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Carminative
Antiseptic
Diuretic
Expectorant
Sedative
Antiphlogistic
Stomachic
Anthelmintic
Volatile oils
• Monoterpene-rich
volatile oils
Some examples:
• Peppermint oil
• Lavender oil
• Lemon oil
• Camphor
• Thyme oil
• Turpentine oil
• Phenylpropane-rich
Volatile Oils
Some examples:
• Cinnamon oil
• Anise oil
• Fennel oil
• Clove oil
• Nutmeg oil
• Peru balsam
• Tolu balsam