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
1 ISOPRENE RULE
6 8 5 7 OH 4 3
2 OH isoprene 1 myrcene geraniol farnesol
O
camphor CO H OH 2 carvon guajol dextropimaric acid
WAYS OF C5 UNITS CONDENSATION „HEAD – HEEL“
monoterpenes sesquiterpenes diterpenes
2 WAYS OF C5 UNITS CONDENSATION
6 5 7
4 8 p-menthane type 3
2 1 type: thujane camphan head-heel 2,6-dimethyloctane pinane carane
8 6 7 5 type of cantharidine 4 3 2 1
heal-heel 2,7-dimethyloctane
6 5 7 type of fenchane 4 3 2 1
heel-side 2,3,6-trimethylheptane
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)
3 BIOGENETIC ORIGIN
H C OH 3 C HOOCH2C CH2CH2OH
(R)-mevalonic acid
BIOGENETIC ORIGIN OF IPP (1) (takes place in cytoplasma of plant cell)
CH COCH CO SCoA CoA SH 2 CH3CO SCoA 3 2 + acetylcoenzyme A acetoacetylcoenzym A
CH3CO SCoA NADP+ HMG-CoA synthase OH NADPH OH CH C CH CO H CoA SH 3 2 2 CH3 C CH2CO2H + CH CH OH HMG-CoA reduktasa 2 2 CH2CO SCoA mevalonic acid -hydroxy--methylglutaryl-CoA 3 H C ATP 3 3 4 C CH2CH2OPP H C ADP 2 3-methyl-3-butenyldiphosphate = isopentenyldiphosphate (IPP) H3C OP -CO C 2 - HOP isomerase H2C CH2CH2OPP H C 3 C 3 2 HO O C CHCH2OPP
H3C 3-methyl-2-butenyldiphosphate = 3,3-dimethylallyldiphosphate (DAPP)
4 BIOGENETIC ORIGIN OF IPP (2) (takes place in plastides)
1 CH3 2 C=O - 1 CH COO 3 2 C=O + Pyruvic acid H + H O C H 3 3 CHO H C OH 4 H 4 C OH 5 CH2OP CH OP 5 2 1-deoxy-D-xylulose-5-phosphate GAP
HO HO 2 4 2 4 1 OP 1 3 3 OP OPP O OH OH OH IPP 2-C-methyl-D-erythritol-4-phosphate 3-methyl-3-butenyl-diphosphate
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
CH CH3 3 C CH OPP C CH OPP PPO CH H C CH 2 CH CH 2 2 + 2 2 2 H2C CH IPP + HOPP CH C H C CH C 3 3 H C CH DMPP 3 3 geranyldiphosphate
PPO CH OPP 2 CH2 CH2 = + CH OPP + 2 CH OPP 2 CH OPP IPP 2 farnesyl-PP IPP geranyldiphosphate farnesyl-PP 2x farnesyl-PP
CH2OPP
squalene geranylgeranyl-PP
5 FORMATION OF BASIC TERPENOIDS
DAPP + IPP
H - P
C10 monoterpenes GERANYL-PP (C10) H - P IPP
C15 sesquiterpenes FARNESYL-PP (C15) H - P : condenzation "head - heel" 2x P-P P - P : kondenzation " heal - heal "
C30 PP H - P squalene
IPP
C30 triterpenes
GERANYL-GERANYL-PP (C20) C19-21 steroids (IPP) (IPP)n n H - P H - P P-P C diterpenes 20 2x gutta-percha cautchuc phytol (trans) (cis) giberillines C40 carotenoids
HEMITERPENES
2 2 1 4 3 1 4 3 CH2OH CH2OH
3-methyl-2-buten-1-ol 3-methyl-3-buten-1-ol
2 O O 2 O O 3 1 4 3 1 4 CH O P O P OH CH2 O P O P OH 2 OH OH OH OH
3-methyl-2-butenyldiphosphate 3-methyl-3-butenyldiphosphate 3,3-dimethylallyldiphosphate (DAPP) isopentenyldiphosphate (IPP)
6 MONOTERPENES
CH OH OH OPP 2 + H O + H - H2O 2 CH2OH geranyl-PP geraniol citronelol ocimene linalol
+ limonene
+ -pinene +
3-carene
GERANIOL; NEROL; LINALOL
CH CH3 3 H3C OH H 6 8 5 7 OH 4 3 H OH 2 1
Geraniol Nerol Linalol
CH CH CH CH 3 3 3 3 1 H CH OH 7 5 3 7 5 3 2 8 6 4 2 8 6 4 2 CH OH H 1 2
7 BICYCLIC MONOTERPENES
camphane linear type p-menthane
pinane fenchane carane thujane
IRIDOIDS
11 4 6 5 3 7 O 8 9 1 10 Iridane Cyclopentanotetrahydropyrane
8 IRIDOIDS
CH GERANYL - PP H O CH O O citronellal iridodial
COOCH3
HO alkaloids O
O Glc loganine
HO O O RO
O O CH2OR HOH C 2 O Glc O O aucubine O Glc valepotriates gentiopikroside
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
9 ACYCLIC SESQUITERPENES
H
2 3 CH2OH
CH3 trans-farnesol (geraniol) CH2OH
2 3 H
CH3 cis-farnesol (nerol) OH
nerolidol (linalol)
SESQUITERPENIC CARBOHYDRATES
H H
H3C CH3
-farnesene trans--farnesene cis--farnesene
10 CYCLIC SESQUITERPENES
5 8 6 8 7 4 9 5 6 7 1 2 9 2 10 4 10 3 1 3 OPP OPP trans, trans - farnesyl-PP cis, trans - farnesyl-PP
+
OPP + carbocation carbocation OPP
14
2 1 9 10 3 8 4 5 7 6 13 bisobolane humulane 15 11 germacrane guajane ( ) cadinane ( ) caryophylane 12 ( ) eudesmane
-BISABOLENE
+ - H+
x cis-farnesyldiphosphate carbocation -bisabolene
O
CH2OH -curcumene turmerone lanceol
11 SESQUITERPENIC LACTONES (Asteraceae)
- H+ HO+ O + precursor
O
oxidation - H+
+ COOH CH2OH CH2OH
OH cyclization O C COOH O
OH
HO H O O O O O O artemisine santonine artabsine O O
ANTIFEEDANTS
Sesquiterpenic dialdehyde COH Plants of Polygonaceae, COH Canellaceae, Winteraceae families
H Mollusces (class Arthropoda) Polygodial Only once the fish try to eat…
12 DITERPENES
+C +C CH 5 5 CH2 2 CH2 OPP OPP OPP
CH2OPP
geranylgeranyldiphosphate
OH
geranyllinalol part of jasmine essential oil
DITERPENS
H3C CH2CH3
CH N CH3 H2C N Mg N
CO H3C N H H3C H COOCH3 H
CH2CH2 COO
chlorofyll a phytol
CH3
H3C O
HO -tocoferol (vitamin E) CH3
O
CH3
O
vitamin K1
13 BASIC TYPES OF CYCLIC DITERPENES
DITERPENES
ACYCLIC MONOCYCLIC BICYCLIC
20 20 20 13 15 12 12 11 14 11 14 12 14 16 15 19 19 13 19 18 13 15 5 11 1 18 18 4 6 9 1 9 10 2 10 8 2 10 8 7 3 5 7 3 5 7 3 2 9 4 4 6
17 8 6 1 16 17 retinol type 16 17 labdane type
TRICYCLIC TETRACYCLIC
15 15 14 14 16
pimarane type abietane type caurane type
MONOCYCLIC DITERPENES
-caroten
CH2OH 2
vitamin A1 (retinol)
CH2OH
vitamin A2 (3-dehydroretinol)
14 BICYKLIC AND POLYCYCLIC DITERPENES
OH OH O HO O
O O O H CH marubiine picrosalvine OH N H OH H atisine
H
HO2C H HO2C H pimaric acid podocarpic acid
TRITERPENES
squalene
squalene-2,3-epoxide O
tetracyclic HO intermediate lanosterol HO cycloartenol
Animals lower and higher Fungi photosyntetizing plants
HO
cholesterol HO -sitosterol HO -amyrine
15 FORMATION OF AGLYCONS OF CARDIOACTIVE GLYCOSIDES
steroidal steroidal saponins alkaloids OH
20
HO HO cholesterol 20-hydroxycholesterol
CH2OH CH3 C O C O
OH HO O H progesterone 5-pregnan-3,14,21-triol-20-on O CH C 3 SCoA C3-unit
O O O O
OHC
OH OH HO HO OH H digitoxigenine hellebrigenine
BIOSYNTHESIS OF TETRATERPENS
geranylgeranyldiphosphate geranyllinaloydiphosphate
phytoene (3 conjugated double bonds, 1 x cis )
H
neurosporine (9 conjugated double bonds, all-trans)
lycopene (11 conjugated doubl bonds, all-trans)
-carotene
-carotene
16 TETRATERPENES
O OH
HO capsanthine
TETRATERPENES
OH 3' 6' 1' 1
3 HO 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.
17 POLYTERPENES
H H C H H H3C 3 H3C H3C H
* n * cautchuc (all - cis) degree of polymerisation 20.000
CH3 CH3 CH3 CH3 * * n H H H H gutta-percha (all - trans) degree of polymerisation 2.000
18