1
T E R P E N O I D S
COMPOUNDS DERIVED FROM MEVALONIC ACID
• The largest and most variable group of natural compounds
(monoterpenes, sesquiterpenes, diterpenes, sesterpenes, triterpenes,
polyterpenes)
• Relative both in general biosynthetic origin and reciprocal structural
relationship
• Formed by multiples of five carbon unit
• Pyrolysis produces carbohydrate isoprene (2-methylbutadiene) →
isoprenoids. Isoprene is not a natural compound.
TERPENOIDS - OCCURRENCE
• Prevalent majority of terpenoids is found free in plant tissues
(Lamiaceae, Asteraceae, Rosaceae, Rutaceae, Apiaceae….)
• Exceptionally glycosides
• Esters with organic acids
• Combination with proteins
• Lower members of group (C10 and C15 substances) are volatile –
distillation with water steam (hydrodistillation) (essential oils –
olea etherea, Etheroleum menthae)
• Higher members (C20 and more) are not volatile – extraction
with organic solvents
2
ISOPRENE RULE
O
OH
OH
CO2H
OH
isoprene
myrcene geraniol
carvon
camphor
farnesol
guajol
dextropimaric acid
1
2
3
4
5
6
7
8
WAYS OF C5 UNITS CONDENSATION
„HEAD – HEEL“
monoterpenes
sesquiterpenes
diterpenes
3
WAYS OF C5 UNITS CONDENSATION
5
6
7
84
2
1
3
5
6 7
8
4
3 2
1
5
4
3 2
7
6
1
head-heel 2,6-dimethyloctane
type: thujane
camphan
pinane
carane
2,7-dimethyloctane
type of cantharidine
heal-heel
heel-side
type of fenchane
2,3,6-trimethylheptane
p-menthane type
BASIC SUBDIVISION OF NATURAL TERPENOIDS
LABELING NUMBER OF C5 OCCURRENCE
HEMITERPENES 1 constituent of ergot alkaloids; some C5 acids
MONOTERPENES 2 volatile constituents of essential oils (geraniol, menthol, camphor)
SESQUITERPENES 3 constituents of essential oils (farnesol, farnesen); some bitter substances (artabsin)
DITERPENES 4 constituents of essential oils, resins, balsams (for example abietic acid); vitamin A;
gibberellins (phytohormones); constituent part of some alkaloids (Aconitum); phytol
(building block of chlorophylls)
TRITERPENES 6 squalene; pentacyclic triterpenes; steroids; cardioactive glycosides; some bitter
substances
TETRATERPENES 8 carotenoids; xanthofylls; some lipophilic plant pigments
POLYTERPENES n cautchuc (cis)
gutta-percha (trans)
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BIOGENETIC ORIGIN
C
OHCH3
HOOCH2
C CH2CH2OH
(R)-mevalonic acid
BIOGENETIC ORIGIN OF IPP (1)
(takes place in cytoplasma of plant cell)
SCoA CH3
COCH2
CO SCoA CoA SH
C CH2
CO2
HCH3
OH
CH2
CO SCoA
CoA SH
CH3
CO SCoA
C CH2
CO2
HCH3
OH
CH2
CH2
OH
C
OPCH3
CH2
CH2
CH2
OPP
C
OH O
C CH2
CH2
OPP
CH3
CH2
C CHCH2
OPP
CH3
CH3
CH3
CO +
+
NADP+
NADPH
mevalonic acid
ATP
ADP
3
-CO2
- HOP
2
3-methyl-3-butenyldiphosphate
acetylcoenzyme A acetoacetylcoenzym A
-hydroxy--methylglutaryl-CoA
= isopentenyldiphosphate (IPP)
3-methyl-2-butenyldiphosphate
= 3,3-dimethylallyldiphosphate (DAPP)
3
23
4
isomerase
HMG-CoA reduktasa
HMG-CoA synthase
5
BIOGENETIC ORIGIN OF IPP (2)
(takes place in plastides)
CH3
C=O
COO-
C
CHO
CH2
OP
H OH
CH3
C=O
COH H
CH OH
CH2OP
H
OP
O OH
OH
OP
OH OH
OH
OPP
Pyruvic acid
+
GAP
1-deoxy-D-xylulose-5-phosphate
+
1
2
3
41 2
3
4
2-C-methyl-D-erythritol-4-phosphate
IPP
3-methyl-3-butenyl-diphosphate
1
2
3
4
5
1
2
3
4
5
Lange B.M., Croteau R.: Biochem. Biophys. 365 (1), 170-174 (1999)
Isoprenoid biosynthesis via a mevalonate-independent pathway in plants:
Cloning and heterologous expression of 1-deoxy-D-xylulose-5-phosphate
reductoisomerase from peppermint.
POLYMERISATION REACTIONS
CH2
CH
C
CH3 CH3
PPO
C
CH3
CH2 CH2
CH2OPP
HOPP
CH
CH2OPPC
CH2
CH2
CH
C
CH3 CH3
CH3
CH2
OPP
CH2
OPP
CH2PPO
CH2OPP
CH2OPP
CH2
CH2OPP
+
+
geranyldiphosphate
IPP
DMPP
+
=
farnesyl-PP
farnesyl-PP
+
IPP
squalene
geranylgeranyl-PP
geranyldiphosphate
IPP
2x farnesyl-PP
6
FORMATION OF BASIC TERPENOIDS
DAPP + IPP
GERANYL-PP (C10)C10 monoterpenes
IPP
H - P
H - P
FARNESYL-PP (C15)C15 sesquiterpenes
IPP
H - PC30 PP
squalene
C30 triterpenes
C19-21 steroids
GERANYL-GERANYL-PP (C20)
2x P-P
C20 diterpenes
phytol
giberillines
C40 carotenoids
gutta-percha
(trans)
cautchuc
(cis)
H - P
H - P
P-P
2x
P - P : kondenzation " heal - heal "
(IPP)n(IPP)n
H - P : condenzation "head - heel"
HEMITERPENES
CH2OH CH2OH
CH2
O P
O
OH
O P
O
OH
OH CH2
O P
OH
O P
OH
OH
O O
3-methyl-2-buten-1-ol 3-methyl-3-buten-1-ol
3,3-dimethylallyldiphosphate (DAPP) isopentenyldiphosphate (IPP)
1 1
11
2 2
2 2
3
3
3 34 4
4 4
3-methyl-2-butenyldiphosphate 3-methyl-3-butenyldiphosphate
7
MONOTERPENES
OPP
CH2
OH
CH2OH
H
+
OH
geranyl-PP
+ - H2O
linalolocimenecitronelolgeraniol
+
+
+
limonene
3-carene
-pinene
H2O
GERANIOL; NEROL; LINALOL
OH
CH3
H
CH3
OH
H
CH3 OH
CH3
CH2OH
CH3
H
CH3 CH3
CH2
OH
H
Geraniol Nerol Linalol
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
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BICYCLIC MONOTERPENES
linear type
camphane
thujane
carane
pinane fenchane
p-menthane
IRIDOIDS
O
1
3
4
56
7
8 9
10
11
Iridane
Cyclopentanotetrahydropyrane
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IRIDOIDS
H
O
CH
O
CH
O
O
O
Glc
COOCH3
OH
O
O
Glc
OH
HOH2C
O
O
O
O Glc
O
CH2ORO
RO
GERANYL - PP
alkaloids
iridodialcitronellal
loganine
aucubine
gentiopikroside
valepotriates
SESQUITERPENES
• THE MOST WIDESPREAD GROUP OF NATURAL COMPOUNDS
• GENERAL ORIGIN IN ORIGINAL CATIONOID PRECURSORE
• BETWEEN SINLE GROUPS SHARP DISTINCTIONS
• OCCURENCE OF SOME GROUPS CHEMOTAXONOMICALLY LIMITED TO
CERTAIN PLANT SPECIES
• USEABLE FOR CHEMOTAXONOMY
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ACYCLIC SESQUITERPENES
3
2
CH2
OH
CH3
H
3
2
H
CH3
CH2OH
OH
nerolidol
cis-farnesol
trans-farnesol
(geraniol)
(nerol)
(linalol)
SESQUITERPENIC CARBOHYDRATES
CH3
H
CH3
H
-farnesene trans--farnesene cis--farnesene
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CYCLIC SESQUITERPENES
8 7
6
1
2 3
4
5
109
OPP
9
8
2
3 4
5
6
7
1
10
OPP
OPP
OPP
cis, trans - farnesyl-PP
trans, trans - farnesyl-PP
+
bisobolane
( ) cadinane
+
germacrane
( ) eudesmane
guajane
humulane
( ) caryophylane
12
3
4 5
6
7
8
9
10
11
12
13
14
15
carbocation carbocation
-BISABOLENE
O
CH2
OH
x
+
- H+
-bisabolenecarbocationcis-farnesyldiphosphate
-curcumene turmerone lanceol
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SESQUITERPENIC LACTONES
(Asteraceae)
O
CH2
OHCH2OHCOOH
O
COOH
OH
C
O
OH
O
O
O
O
O
OH
O
O
O
H
O
+
- H+
HO+
+
- H+oxidation
cyclization
artabsine artemisine santonine
precursor
ANTIFEEDANTS
Sesquiterpenic dialdehyde
Plants of Polygonaceae,
Canellaceae, Winteraceae
families
Mollusces (class Arthropoda)
Only once the fish try to
eat…
COH
COH
H
Polygodial
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DITERPENES
OPP
CH2
OPP
CH2
OPP
CH2
CH2
OPP
OH
+C5
+C5
geranylgeranyldiphosphate
geranyllinalol
part of jasmine essential oil
DITERPENS
N
N N
N
Mg
CH3
CH2
CH3
CH3
CO
CH2
CH2
HCH3
H
CH3
CHCH2
H
COOCH3
COO
O
CH3
CH3
CH3
OH
CH3
O
O
phytolchlorofyll a
-tocoferol (vitamin E)
vitamin K1
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BASIC TYPES OF CYCLIC DITERPENES
15
14
15
1614
DITERPENES
ACYCLIC MONOCYCLIC BICYCLIC
TRICYCLIC TETRACYCLIC
pimarane type abietane type caurane type
1
23
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
2
6
7
11 14
1
3 4 5
8
9
10
1
3
4
5
8
9
10
13 15
12
13
14
15
16
12
16 17
18
19
20
17
1819
20
2
6
7
11
labdane typeretinol type
MONOCYCLIC DITERPENES
CH2OH
CH2
OH
-caroten
2
vitamin A1 (retinol)
vitamin A2 (3-dehydroretinol)
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BICYKLIC AND POLYCYCLIC DITERPENES
O
OOH
O
O
OH
OH
H
HHO2
C
H
HHO2C
OH
CH
O
OH
H
N H
marubiine picrosalvine
pimaric acid podocarpic acid
atisine
TRITERPENES
OH
OH
OH
OH
OH
O
squalene
squalene-2,3-epoxide
lanosterol
cycloartenol
cholesterol
-sitosterol
-amyrine
lower and higher
photosyntetizing
plants
tetracyclic
intermediate
Animals
Fungi
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FORMATION OF AGLYCONS OF CARDIOACTIVE
GLYCOSIDES
OH OH
OH
C
O
CH3
O
C
OH
CH2
OH
O
H
OH
O
OH
H
OH
O
O
OH
OH
OH
O
OHC
CH3
C
O
SCoA
steroidal
saponins
steroidal
alkaloids
cholesterol 20-hydroxycholesterol
progesterone 5-pregnan-3,14,21-triol-20-on
C3-unit
digitoxigenine hellebrigenine
20
BIOSYNTHESIS OF TETRATERPENS
H
geranylgeranyldiphosphate
geranyllinaloydiphosphate
phytoene (3 conjugated double bonds, 1 x cis )
neurosporine (9 conjugated double bonds, all-trans)
lycopene (11 conjugated doubl bonds, all-trans)
-carotene
-carotene
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TETRATERPENES
O OH
OH
capsanthine
TETRATERPENES
OH
OH
1
3
1'
3'
6'
Luteine
(3R,3'R,6'R)-,-carotene-3,3'-diol
3,3'-dihydroxy--carotene
• Belongs to carotenoids of xanthophyll group
• Contains the same chromophore as α-carotene, it is isomeric with zeaxanthine.
• Yellow pigment, present together with carotene and chlorophyll in all green
plant parts
• Present in many yellow and red flowers and fruits, it was observed also in
animals, for example in feathering, yolk, and in corpus luteum.
• Can be present as free substance or as ester; it possesses no activity of
vitamine A.
• Luteine was firstly obtained in crystalline state 1907 by Willstätter from stinking
nettle, later from chicken yolk. Structure was resolved by P. Karrer in 1951.
• Protectum, Vitalux Plus 6, Ocuvite … macular defects of eye.
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POLYTERPENES
**
CH3
CH3 CH3 CH3
n
H H H H
* *
CH3
CH3
CH3
CH3
n
H H H H
cautchuc (all - cis)
gutta-percha (all - trans)
degree of polymerisation 20.000
degree of polymerisation 2.000