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7/23/2019 Natural Product Chemistry (Chm3202)Revised (1) (2)
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NATURAL
PRODUCTCHEMISTRY
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Examples of important
drugs obtained from plants
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Is the study of natural extracts which are
obtained from natural resources.
Natural product chemists extract, purify,and finally analyse compounds which are
obtained from living cells.
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Techniques used are:
1. Column chromatography, CC2. Gas chromatography, GC
3. Thin layer chromatography, TLC
4. High pressure liquid chromatography,
HPLC
5. Paper chromatography
6. Electrophoresis
7. Ion exchange chromatography
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These techniques allow for the separation
and purification of compounds which are
present in very small quantities. Structural elucidation of the unknown
compounds are usually carried out using
spectroscopic techniques such as:
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Ultraviolet spectroscopy (UV)
Infra red spectroscopy (IR)
Nuclear magnetic resonance spectroscopy
(NMR) and
Mass spectroscopy (MS)
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Primary and Secondary
Metabolism Primary metabolites are carboxylic acids
of the Krebs cycle, a-amino acids,
carbohydrates, fats and proteins. Hence, primary metabolism refers to the
photosynthesis process producing these
low molecular weight compounds. These are the starting materials – the
precursors – of the secondary metabolites.
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Principal Pathways
The main streams of secondary
metabolism is outlined in the chart.
Most metabolites originate from a verylimited number of precursors.
They are linked to primary metabolism.
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Acetic acid has a central position in the form of
its thioester acetyl, CoA.
It is produced in the cell, from pyruvic acid orfatty acids,or it may be directly formed from
acetate and coenzyme A with ATP.
C6H12O6 CH3CCOOH
O
CH3CHCO2H
OH
C6H12O6 + 6O2 6CO2 + H2O + energy
Glucose
Glucose Pyruvic acid Lactic acid
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From acetic acid, mevalonic acid is
derived, from which via 3,3-dimethylallyl
pyrophosphate and the isomeric
isopentenyl pyrophosphate – the isoprene
unit – the terpenoids are formed.
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From carbohydrates, shikimic acid is
derived which is the key to a wealth of
aromatics.
It is also important to note that amino acid
is the important precursor to a great
variety of nitrogen containing compounds.
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Major Pathways:
• Shikimic acid – aromatic acids
• Acetate / polyketide –fats, oils,
aromatic and poly aromatic compounds• Mevalonic acid – Terpenoid: mono-,
sequi-, di-, triterpenoids.
• Mixed pathway
• Alkaloid
• Miscellaneous
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Several groups of metabolites have mixedbiogenesis; i.e. an intermediate or
metabolite from one principal pathway acts
as a substrate for another metabolite from
a different pathway.
Thus, flavonoids are derived from a
polyketide (three acetate units) and a
cinnamic acid (shikimic acid)
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The indole alkaloid comes from shikimateand a monoterpene (loganin)
In the past natural products were classified
according to structure or biological origin.
The biosynthetic scheme groups the
compounds according to the synthetic
route employed by the cell. There is
overlap.
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There are 3 principal pathways: shikimic,
polyketide, and mevalonic pathways.
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The Shikimic Acid Pathway
A very large number of compounds exhibit
a characteristic C6-aromatic-C3-side chain
structure. E.g. aromatic amino acids,
cinnamic acids, coumarins, flavonoids,lignin constituents, etc.
These come from a common origin.
It was found that erythrose-4-phosphate
starts the biosynthetic pathway leading to
shikimic acid.
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The biosynthesis of these compounds was
elucidated by mutant studies of E.coli by
Davis and Sprinson.
Shikimic acid was isolated as early as1885 by Eykman from the Japanese plant,
Illicium anisatum long before we were
aware of its biosynthetic significance.
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The biosynthesis pathway begins with
D-erythrosephosphate and
phosphoenolpyruvate (PEP) combining via
an aldol condensation.
Both these compounds were initially
derived from D-glucose.
The aldol condensation is aided by an
enzyme which adds on to the
phosphoenolpyruvate molecule to form 3-deoxy-D-arabinoheptulosonate-7-
phosphate (DAHP)
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Ring closure of the heptulose derivative
(3,7-dideoxy-D-arabino-2,6-diulosonicacid) gives 3-dehydroquinic acid.
Removal of 1 H2O molecule from
3-dehydroquinic acid yields 3-dehydroshikimic acid; this acid is reduced
to shikimic acid.
At the pH of living organism, this acidexists in its anionic form, the shikimate ion.
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OH
OH
HO
HO O
Shikimic acid
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Phosphorylation of the shikimate anion
with adenosine triphosphate gives
shikimate-3-phosphate which then reactswith another molecule of
phosphoenolpyruvate (PEP) to yield
5-enolpyruvylshikimate-3-phosphate
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OH
OH
O
O O-
P
shikimate-3-phosphate
-H+
enzyme
surface O-
OH
O
O O-
P
O
CH2
O-
O
P
H
+
PEP
O-
OO
HH
H
O
P
EnzOH
O
O O-
P
O-
O
O
OH
O
O O-
P CH2
enzyme
5-enolpyruvylshikimate-3-phosphate
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5-enolpyruvylshikimate-3-phosphate
converts to chorismate by elimination (1,4
with respect to Hydrogen and Phosphate) Enzyme assistance is once more involved
in this conversion.
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We now have the starting material for the biosynthesis ofnatural aromatic compounds.
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Shikimic Acid
The structure of shikimic acid wasdetermined chemically through the
following methods:
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The acid was optically active and formed
the triacetate when reacted with acetic
anhydride.
This reaction indicated the presence ofthree hydroxyl groups in the molecule.
It reacted with Br 2 (1 mole) and also with
H2 to form dehydroshikimic acid (A).
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HO O
OH
OH
HO
1
2
3
45
6 H2 / Pt
HO O
OH
OH
HO
Shikimic acid 1,2-dehydroshikimic acid
(A)
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HO O
OH
OH
HO
1
2
3
45
6
HO O
OH
OH
HO
Shikimic acid 1,2-dibromoshikimic acid
Br2
Br
Br
HO O
OH
OH
HO
1
2
3
45
6
HO O
OAc
OAc
AcO
Shikimic acid Triacetate shikimic acid
Ac2O
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All the 3 hydroxy groups were shown to be
next to each other by oxidising the methyl
ester of the trihydroxy dehydroshikimicacid with 2 moles of periodic acid to give
the dialdehyde (B).
HO O OH C O
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HO O
OH
OH
HO
OH3C O
OH
OH
HO
CH3OH
H
+
OH3C O
OO
HIO4
dialdehyde
(B)
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The dialdehyde reacts with Bromine water to
give the diacid (C).
OH3C O
OO
OH3C
OO OH
Br2 water
OH
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The diacid is hydrolysed by alkali to give the
triacid (D), tricarbalic (tricarboxylic acid)
OH3C
OO OH
OH
HO O
OO OHHO
Tricarbalic acid(D)
OH
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Methylshikimate reacts with periodic acidunder carefully controlled conditions to
form the dialdehyde (E), which in turn is
oxidised to the unsaturated tri-acid (F),transaconitic acid by oxidation with
peroxypropionic acid and followed by
hydrolysis with base.
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OH3C O
OH
OH
HO
OH3C O
OO
HO O
OO OH
HIO4
C2H5C
OOH
O
2 mol then OH-
MethylshikimateDialdehyde
(E)
Trans-aconitic
acid
(F)
OH
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The C7 skeleton of shikimic acid is the
precursor in the biosynthesis of various
natural products. This include importantamino acids such as p-aminobenzoic acid,
heterocyclic amino acids such as
tryptophan and galotanin and depsideswhich involve galic acid.
COOH
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OH
OH
HO
COOH
NH2
p-aminobenzoicacid
Folic acid
COOH
NH2
anthranilate(B)
N
COOH
NH2
H
Indole
C2N
Tryptophan
(A)
COOH
OH
OH
HO
Galic acid
Galotanin
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The amino acid tryptophan (A) isnecessary for the metabolism processes in
mammals.
In plants tryptophan is formedbiosynthetically from anthranilate (B) by
the addition of a 5C chain.
Tryptophan is an indole derivative.
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Melanin is a dark pigment present in
plants and animals.
This pigment is responsible for the colourof the hair and the skin colour of human
beings.
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Another class of dark coloured pigment in
plants is catechol which is derived from
the oxidation of phenol. This pigment is referred to as catechol
melanin and is responsible for the brown
colour of cut apples and pears.
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Indoliacetic acid (heteroauxin) is a plant
growth regulator.
This compound controls the formation ofthe new cells in plants and at the growing
tips.
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The Acetate Pathway
C6H12O6 CH3CCOH + CH3CHCOHOO OH
O
glucose pyruvic acid lactic acid
In biochemical situations, the pH of the
media is ~7; hence, the carboxylic acidexists in its conjugate base form.
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Therefore,Pyruvic acid pyruvate and
Lactic acid lactate
Pyruvate then acetate
Acetate is the starting material for the
biosynthesis of complex compounds.
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Acetyl coenzyme A, CH3COSCoA
Plays an important role in many metabolicprocesses.
OO
O
CH3CCOH + CoASH + NAD+
pyruvicacid
coenzymeA
nicotinamideadenine dinucleotide
CH3CSCoA + NADH + CO2 + H+
acetyl coenzyme
A
reduced form
of NAD
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Acetyl coenzyme A is the basic unit for thesynthesis of complex natural products.
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Fatty acid
Fats was one of the first natural products
to be studied by chemists.
Fats are glycerol esters. A big part of the natural fatty acid are
straight chain alkanoic acids with an even
number of C atoms.
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They also have double or triple bonds,
hydroxy groups or epoxy or carboxylic acidgroups.
Common fatty acids in living tissues are
stearic acid, oleic acid,palmitic acid andlinoleic acid.
Alternate arrangements (ie at 1, 4, 7) of
the cis-double bonds on these acids areespecially for most of the unsaturated fatty
acids.
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COOH
Palmitic acid (C16)
COOH
Stearic acid (C18)
COOH
Oleic acid (C18)
cis-octadec-9-enoic acid
COOH
Linoleic acidcis,cis-octadec-9,12-dienoic acid
COOH
Arachidonic acid (C20)
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Fatty acids usually exist as glycerol esters
(triglyceride and lecitin) or cholesterol
esters or wax esters. All these compounds are derived from
long chain fatty acids and are known as
lipids.
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Lipid chemists have a special way todenote these fatty acids:
Palmitic acid = 16:0
Stearic acid = 18:0Oleic acid = 18:1 (9C)
Linoleic acid = 18:2 (9C, 12C)
Arachidonic acid = 20:4 (5C, 8C, 11C, 4C)
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CH2 O
CH
CO(CH2)14CH3
O CO(CH2)12CH3
CH2 O CO(CH2)16CH3
A triglyceride
Natural fats are mixtures of triglycerides
like the one shown above and maybe with
di- and mono-glyceride.
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Biosynthesis of Fatty Acids
Acetic acid is the precursor for the synthesis offatty acids.
Acetic acid is first converted to a more reactive
form, the acetylcoenzyme A.
CH3CSCoA + HS-ACP
O
CH3CSACP
O
Acetyl coenzymeA
Acyl
carrierprotein
s-acetyl acylcarrier protein
+ HSCoA
coenzyme A
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A second molecule of acetylcoenzyme A reacts
with HCO3-
(bicarbonate) to yield malonylcoenzyme A.
CH3CSCoA + HCO3-
O
Acetyl coenzyme
A
-OCCH2CSCoA
O O
+ H2OX
Malonylcoenzyme A
X
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The formation of malonyl coenzyme A is
followed by an acyl transfer reaction whichbonds the malonyl group to an acyl carrier
protein.
-OCCH2CSCoA
O O
Malonylcoenzyme A
+ HS-ACP
Acylcarrierprotein
-OCCH2CS-ACP
O O
s-malonyl acylcarrier protein
+ HSCoA
coenzyme A
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A C-C bond is formed between the a-carbon in
the malonyl group and the carbonyl carbon ofthe acetyl group.
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Reduction of the C=O group of the acetoacetyl
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Dehydration of the b-hydroxy group of the acyl
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Thus, the biosynthesis of hexadecanoic acid
(palmitic) can be represented by the followingequation:
Details are:
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Details are:
CH3CSACP + COOHCH2CSACP
O O
CH3CCH2CSACP
O O
+ CO2 + -SACP
CH3CH2CH2CSACP
COOHCH2CSACP
CH3CH2CH2CCH2CSACP + CO2 + -SACP
O
O
OO
CH CH CH CH CH CSACP
O
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CH3CH2CH2CH2CH2CSACP
COOHCH2CSACP
CH3(CH2)4CCH2CSACP + CO2 + -SACP
CH3(CH2)4CH2CH2CSACP
COOHCH2CSACP
CH3(CH2)6CCH2CSACP + CO2 + -SACP
O
OO
O
O
OO
O
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COOHCH2CSACP
CH3(CH2)6CH2CH2CSACP
CH3(CH2)8CCH2CSACP + CO2 + -SACP
CH3(CH2)8CH2CH2CSACP
COOHCH2CSACP
O
OO
O
O
CH (CH ) CCH CSACP + CO + -SACP
OO
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CH3(CH2)10CCH2CSACP + CO2 + SACP
CH3(CH2)10CH2CH2CSACP
COOHCH2CSACP
CH3(CH2)12CCH2CSACP + CO2 + -SACP
CH3(CH2)12CH2CH2CSACP CH3(CH2)14CSACP
S-Hexadecanoyl acyl
carrier protein
O
O
OO
O O
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Flavonoid
The name flavon is given to compounds whichcontain the phenylbenzopyrone skeleton as
shown below:
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Hence, flavons are heterocyclic compunds
of oxygen.
They are an important group of
compounds in the natural yellow pigment.
Flavonols (3-hydroxyflavon) and flavanons
(2,3-dihydroxyflavon) as well as
anthocyanin (flavilium salt) usually exist
together with flavon in the same plant.
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This group of compounds is calledflavonoid.
Flavonoids are present in the ferns as well
as in higher plants.
It usually has hydroxyl groups at 3,5,7,3’
and 4’ as in quercetin and also usually
exists as glycosides like
Kaempherol-7-rhamnoside.
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Flavonoids contribute to the beauty and
splendour of flowers and fruits in nature.
The flavones give yellow or orangecolours, the athocyanins red, violet, or
blue colours i.e. all the colours of the
rainbow but green.
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The flavonoids play a major role in relation
to insects pollinating or feeding on plants
but some flavonoids have a bitter taste,repelling certain caterpillars from feeding
on leaves.
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The flavonoids are structurally
characterized by having two hydroxylated
aromatic rings A and B joined by a 3C
fragment.
One OH group is often linked to a sugar.
Several substructures can be
distinguished: chalcones, flavones,
isoflavones, aurones, and anthocyanidins.
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Structures of Flavonoid Compounds
HO OH
O
OH
OH
B
A
Butein (a chalcone)
2'
3'
4'
5'
6'
1
2
3
4
5
6
HO O
O
OH
OH1'
6'
5'
4'
3'
2'
OH
8
7
6
5 4
3
2
1
Luteolin (a flavone)
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HO O
O
OH
Daidzein (Isoflavone)
HOO
CH
OH
OH
O
Sulphuretin (Aureone)
HO O
OH
OH
OH
OH
Cyanidin (Anthocyanidin)
2’-Hydroxy-substituted chalcones cyclize easily
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2 Hydroxy substituted chalcones cyclize easily
to flavones, the structure of which is stabilized
by hydrogen bonding at C-4O and C-5O.
HO OH
O
OH
a chalcone
2'
OH
HO O
O
OH
O5 4
H
Naringenin (a flavanone)
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The structural determination of Chalcone
was accomplished by alkaline degradation
which gave acetophlorophenone, p-hydroxybenzaldehyde, phloroglucinol, and
acetic acid.
OH
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HO OH
O
a chalcone
2'
OH
HO OH
C
OH
CH3
O
acetophlorophenone
+
OH
OHC
p-hydroxybenzaldehyde
OH
-
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HO OH
C
OH
CH3
O
OH-
OHHO
OH
+ CH3COOH
Phloroglucinol
acetic acid
Acetophlorophenone
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Anthocyanidins were related to 3-
hydroxyflavones by reduction of the
carbonyl group followed by treatment withacid.
OH OH
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HO O
O
OH
OH
OH
LiAlH4
HO O
OH
OH
OH
3
OH
HO O
OH
OH
OH
H+
cyanidin (an anthocyanidin)
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The structure of flavone was initially
determined using alkaline hydrolysis
(Kostanecki, 1893). Chrisin (C) C15H10O4 when heated with
KOH gave phloroglucinol, acetic acid,
benzoic acid and benzophenone.
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HO O
OOH
OH-
Chrisin (C)(a flavone)
OHHO
OH
Phloroglucinol
+ CH3COOH
acetic acid
+COOH
benzoic acid
+
C
O
benzophenone
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For polyhydroxyflavones, methylation ofthe hydroxyl groups before hydrolysis is
important because phenol is easily
oxidised in alkaline medium.
New flavones are usually identified by
comparing their spectra with spectra of
known flavones or by comparison of the
colours with that of known flavones.
Synthesis of flavones & flavanone
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Synthesis of flavones & flavanone
OHHO
OH
Phloroglucinol
+
C
CH2
Ar
C OEt
O
O
A keto ester
vacuum
C
HO Ar
OH O
OH O
HO
OH
O Ar
O
a flavone
Rearrangement (intramolecular) within molecule
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Rearrangement (intramolecular) within molecule
of o-benzoyloxyacetophenone
O
C
C
O
Ar
CH2
H
O
OH
C
C
H
H
Ar O
O
O Ar
H
O
A Flavone
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2’-hydroxy-substituted chalcones cyclize easily
to flavanones.
OH
OOH
H
OH
HO2'
Isomerase
O
OO
H
OH
HO
H
H
Naringenin(a flavanone)
4
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Anthocyanin
Red colour, purple and blue colours of
flowers, berries, and leaves during autumn
are all due to the anthocyanin such ascyanin.
Anthocyanin are glycosides of flavilium
salts.
OH
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O
Oglucose
Oglucose
HO
OH
Cyanin (an anthocyanin)
Contains the basic skeleton of flavone and was
formed by the reduction of quercetin to cyanidin.
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O
O
OH
OH
OH
OH
HO
O
OH
OH
OH
OH
HO
Quercetin
Cyanidin(an anthocyanin)
Anthocyanin is biosynthesized from a flavanonethrough dihydroflavanol
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through dihydroflavanol.
O
OH
O
OH
OH
OH
HO
O
OH
OH
OH
OH
HO
H
H+
OH
H+
O
OH
OH
OH
OH
HO
Cyanidin
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TERPENES
We have already looked at how some
secondary metabolites were
biosynthesized from acetate through thecondensation of linear C2 units.
We shall now look at how the acetate units
are combined in a different form to yieldmevalonic acid which is then converted to
different products such as terpenes.
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These compounds are found naturally in
living organisms.
They were first isolated from plants and
flowers which possess a fragrant smell.
These have long been of interest in the
olden days.
Since the 19th century, the structures of
some components of the essential oils
isolated from plants have been
discovered.
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Most of these components were
unsaturated C10H16 hydrocarbons.
These compounds were named terpenes.
Apart from hydrocarbons, there were also
alcohols and ketones with similar
skeletons.
All these compounds are called
terpenoids.
These compounds have a carbon skeleton
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These compounds have a carbon skeleton
which can be split into two C5 units.
These C5 units are called isopentene units orisoprene units.
Two isopreneunits
Limonene
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C10 compunds are known as
monoterpenes. C15 compounds are called sesquiterpenes,
C20 as diterpenes, C30 as triterpenes, and
C40 as tetraterpenes. These compounds are classified under
terpenes (or terpenoid or isoprenoids) if
their structures can be divided into
isoprene units.
CH
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C CH
CH3
CH2H2C
Isoprene(2-methyl-1,3-butadiene)
tail
head
Two isoprene units joined head to tail.
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Isoprene units in farnesol
OH
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Most terpenes contain one or more rings.
For e.g. a-selinene has 3 isoprene units.
CH3
CH2CH2
H3C
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12
13
tail
head
Isoprene units in squalene (C30-triterpene)
Other examples of terpenes are as follows:
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-phellandrene
(monoterpene)
OH
Methol (peppermint)(monoterpene)
C H
O
Citral (lemon grass)
(monoterpene)
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Sesquiterpenes (C15)
HCH2CH2
OH
-selinene
(celery)
Farnesol
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Diterpene (C20)
OH
Vitamin A
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Triterpene (C30)
Squalene(shark liver oil)
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Tetraterpene
-carotene
(
-carotene Vitamin A)
C40 2 x C20
The Biosynthesis of Terpenes
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The Biosynthesis of Terpenes All terpenes and steroids have the same
biosynthetic sources.
Terpenes can be said to be biosynthesized from
mevalonate (mevalonic acid) via isopentenyl
pyrophosphate.
1. 3 CH3COH
oseveral
steps HOCCH2CCH2CH2OH
O CH3
OH
acetic acid mevalonic acid
In the 2nd step, mevalonic acid is converted to 3-
th l 3 b t l h h t (i t l
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methyl-3-butenylpyrophosphate (isopentenyl
pyrophosphate)
HOCCH2CCH2CH2OH
O CH3
OH
Mevalonic acid
several
stepsCCH2CH2OPOPOH
CH3
H2C
O O
OHOH
OPP
Isopentenyl pyrophosphate(a biological isoprene unit)
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Isopentenyl pyrophosphate undergoes an
enzyme catalyzed reaction and getsconverted to dimethylpyrophosphate.
OPP
H+
-H+OPP
H H
H+
-H+
OPP
Dimethylpyrophosphate
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Dimethylpyrophosphate is more reactive
than isopentenylpyrophosphate tonuclephilic reagents.
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Formation of C-C bond in terpenebiosynthesis.
OPP
OPP
x
-(OPP-)
OPPx
10-C CarbocationDimethylpyrophosphate
Isopentenylpyrophosphate
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Loss of a proton from the carbocation to
give an alkene.
OPP
H H
OPP
Geranylpyrophosphate
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Hydrolysis of the ester group yields
geraniol, a monoterpene which exists inthe rose essential oil.
OPP
Geranylpyrophosphate
H2O
OH
Geraniol
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Geranylpyrophosphate is an allylicpyrophosphate and likedimethylallylpyrophosphate can react as
an alkylation reagent to isopentenylpyrophosphate.
OPP
+
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Geranylpyrophosphate
xOPP
+
Isopentenylpyrophosphate
OPP
x
H H
-H+
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OPP
Farnesyl pyrophosphate
H2O
OH
Farnesol
Questions:
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Questions:
Write the steps for the biosynthesis of
geranylgeraniol from farnesyl
pyrophosphate
OPP
Farnesyl pyrophosphate
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Higher terpenes are not formed by the
continuous addition of C5 units but bycoupling of simple terpenes.
Therefore, triterpenes are formed by the
coupling of two farnesyl pyrophosphatewhile tetraterpenes (C40) from two
molecules of
geranylgeranilpyrophosphate.
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The formation of the C-C bond is a
complex process and involves the joining
of tail to tail.
The formation of geraniol and farnesol can
be said to be a dimerization of alkenes.
We now look at the formation of a cyclic
monoterpene.
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OPP
OPP
+ OPP-
Geranylpyrophosphate Nerylpyrophosphate
a tertiarycarbocation
-H+
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H2O HO
Limonene
-terpineol
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Loss of a H+ gives Limonene a natural
product present in citrus.
Addition of H2O to the carbocation gives a-terpineol a natural product also.
The same carbocation can also give
bicyclic monoterpenes.
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x x x
xxx
x
y
y
y
yy
y y
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H3C
xH
H
-H+
x
H
x
+
-Pinene -Pinene
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O
HH
O
HH
OH
Borneol
Formation of isopentenyl
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p y
pyrophosphate
CH3CSCoA + -OOCCH2CSCoA
O O
CH3CCH2CSCoA + CO2
O O
AcetylCoenzyme A
MalonylCoenzyme A
AcetoacetylCoenzyme A
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We have seen how mevalonic acid is
formed from 3 molecules of acetic acid. From mevalonic acid isopentenyl
pyrophosphate is formed.
Isopentenyl pyrophosphate is used in thebiosynthesis of terpenes.
We now look at how mevalonic acid is
formed from acetate.
CH3CSCoA
O
CH3CCH2CSCoA
O O
+
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CH3CSCoACH3CCH2CSCoA
Acetyl
Coenzyme A
Acetoacetyl
Coenzyme A
+
CH3C CH2CSCoA
OH
CH2COH
O
O
-hydroxy- -methylglutaryl
coenzyme A (HMG CoA)
CoASH +
coenzyme A
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CH3C CH2CSCoA
OH
CH2COH
O
O
-hydroxy- -methylglutaryl
coenzyme A (HMG CoA)
CH3C CH2CH2OH
OH
CH2COH
O
O
Mevalonic acid
Mevalonic acid has 6C.
Loss of a C atom changes it to isopentenyl
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Loss of a C atom changes it to isopentenyl
pyrophosphate
C CH2
COHH3C
CH2CH2OH
-O
O
Mevalonate
C CH2
COPO3
2-H3C
CH2CH2OPP
-O
O
-PO43-
-CO2
CCH2CH2OPP
H3C
H2C