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TITLE
INTRODUCTION OF TERPENOIDS
CLASSIFICATION OF TERPENOIDES
TETRACYCLIC TRITERPENOIDS
PENTACYCLIC TRITERPENOIDS
NEW SKELETON OF TRITERPENOIDS
STRUCTURE OF NEW SKELETON TRITERPENOIDS
REFERENCES
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1. INTRODUCTION
1.1 Definition 1-4
1
1.3 Occurrence 3
The simple mono and sesquiterpenoids are the chief constituents of the essential
oils. The di and triterpenoids which are not steam volatile are obtained from plant, tree,
gums and resin. The tetraterpenoids constitute a group of compounds called
carotenoids. This group includes carotenes, xanthophyllis and carotenoidic acids.
Rubber is the most important polyterpenoids.
1.4 General properties of Terpenoids 2
As far as physical properties of terpenoids are concerned, most of them are
colourless liquids which are lighter than water and boil between 150C and 180C. A few
are solids which are lighter than water, volatile in steam, usually highly refractive and
insoluble in water but soluble in organic solvents. Many of these are optically active.
The various general chemical properties of terpenoids are as follows: 2
They are unsaturated compounds (open chain or cyclic with one or more carbon
atom rings) having on or more double bonds. Consequently, terpenoids undergo
addition reactions with hydrogen, halogens, halogen acids, etc. some of them
form hydrates. They also form characteristic addition products with NO 2, NOCl
and NOBr. These addition products are founds to be useful in the identification of
terpenoids. A number of addition products have antiseptic properties.
As they have olefinic bonds, they are very easily oxidised nearly by all the
oxidising agents.
A number of terpenoids are labile and hence readily isomerised in the presence of
acids into more stable forms.
1.5 Isolation is carried out in two steps follow: 2 Lets discuss it one by one.
I.
Expression method: This method the plant material is cut in to small pieces.
Then these pieces crushed to get the juice which is screened to remove the larger
particles. After screening the juice is centrifuged in a high speed centrifuge
machine when one-half of the oil is extracted oil remains with the residue. From
this residue, inferior quality of the oil is obtained by distillation.
Steam distillation method: This method is the one most widely used method. In
this plant materials are macerated and then steam distilled to get the essential oils
in to the distillate from which these are extracted by using pure organic solvent
like light petroleum and solvent is then removed by distillation under the reduced
pressure .
II.
Separation of terpenoids from essential oils: The essential oils obtained from
step 1 generally contain number of terpenoids and these are separated by various
physical and chemical method.
a. Chemical method:
When essential oils containing alcohols are treated with the phthalic anhydride
to form diesters. The primary alcohol react with pthalic anhydride readily and
tertiary alcohol do not react at all.After extracting with sodium bicarbonate,
diesters are decomposed by alkali to perent triterpenoid alcohol.
Terpenoids alcohol and ketones are separated from essential oils by forming
their adducts with common carbonyl reagent like NaHSO3, 2-4-dinitro phenyl
5
used
as
adsinbents
for
separating
the
terpenoids.
2. CLASSIFICATION OF TERPENOIDS
The terpenoids have a general formula (C 5H8)n and have of n is used as a basis of
classification:3
Table no. 1
Class
1) Hemiterpene
2) Monoterpenes
3) Sesquiterpenes
4) Diterpenes
5) Triterpenes
6) Tetraterpenes
7) Polyterpenes
Classification of tepenoides
Molecular formula
C5 H8
C10 H16
C15 H24
C20 H32
C30 H48
C40 H64
(C 5H8 )n
The sesterterpenoids have been discovered recently. The example of this class
called solanesol, an acyclic unsaturated alcohol was discovered in 1956. In addition to the
hydrocarbons in each class given in Table, oxygenated compounds like alcohols,
aldehydes, ketones are also known which occur in nature.
Each class of terpenoids has been further subdivided into subclasses according to
the number of rings present in the molecule.
(1)
(2)
(3)
(4)
(5)
(6)
pentacyclic triterpenoids.
The steroidal saponins are less widely distributed in nature than the pentacyclic
tritetpenoid type. Phytochemical surveys have shown their presence in many
monocotyledonous families, particularly the Dioscoreaceae (e.g. Dioscorea spp.),
Amaryllidaceae (e.g. Agave spp.) and Liliaceae (e.g. Yucca and Trillium spp.). In the
dicotyledons the occurrence of diosgenin in fenugreek (Leguminosae) and of steroidal
alkaloids in Solanum (Solanaceae) is of potential importance. Some species of
Strophanthus and Digitalis contain both steroidal saponins and cardiac glycosides.
Examples of saponins and their constituent sugars are sarsaponin, digitonin, gitonin,
dioscin.
Steroidal saponins are of at pharmaceutical importance because of their
relationship to compounds such as the sex hormones, cortisone, diuretic steroids, vitamin D
and the cardiac glycosides. Some are used as starting materials for the synthesis of
these compounds. Diosgenin is the principal sapogenin used by industry but most
yams, from which it is isolated, contain a mixture of sapogenins in the glycosidic
form.
As with cardiac glycosides. The stereochemistry of the molecule is of some
importance, although not so much so for cortisone manufacture. Natural sapogenins differ
only in their configuration at carbon atoms 3, 5 and 25, and in the spirostane series the
orientation at C-22 need not be specified (steroidal alkaloids). Mixtures of the C-25
epimers e.g. diosgenin (4 5, 25-spirosten-30-ol) and yamogenin (25-spirosten-30-ol) are
8
of normal occurrence and their ratio, one to the other, is dependent upon factors such as
morphological part and stage of development of the plant. In some instances in the
plant, the side-chain which forms ring F of the sapogenin is kept open by glycoside
formation as in the bisdesmosidic saponin sarsaparilloside of Smilax aristolochiaefolia.
3.1 Biogenesis of steroidal saponins5
Steroidal saponins arise via the mevalonic acid pathway. A scheme for the
R
hecogenin for corticosteroids, to other sources of diosgenin and to the use of the steroidal
alkaloids of Solanum species Total synthesis also became economically feasible and is
now much used. Recently, the economics of steroid production have again changed in that
China is now exporting large quantities of diosgenin; it is of high quality (although the
fact is of no significance commercially, it is free of the 25 isomer yamogenin) and is
reasonably priced. Three of the many Dioscorea spp. found in China and used
commercially are given in Table no.1, the tubers of these yield 2% of diosgenin, with the
average content of diosgenin for the main areas of production being l%.
Hecogenin
Sarsapogenin
Sarmentogenin
Species
Dioscorea sylvatica
D. mexicana, D.composita
D. tokora
D. deltoidea
Agave sisalana
A. rigida
Yucca saponin
Strophanthus saponin
Location
Transvaal and Natal
Mexico and Center America
Japan
India
America and Kenya
Mexico
Center Anerica
africa
3.3 Sisal: Hecogenin is obtained commercially as the acetate in about 0.01% yield from
sisal leaves (Agave sisalana). In East Africa, from leaf 'waste' stripped from the leaves
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during removal of the fibre. A hecogeonin containing 'sisal concentrate' is produced. From
this the 'juice' is separated and allowed to ferment for 7 days. The sludge produced
contains about 80% of the hecogenin originally present in the leaves; steam at 1380 kPa
pressure is employed to complete the hydrolysis of the original glycosides. By filtration
and drying a concentrate containing about l2% hecogenin and varying amounts of other
sapogenins is produced.7-9
3.4 Fenugreek seeds: A spice cultivated in many parts of the world and derived from
Trigonella foenum-graecum (Leguminosae). Different commercial samples vary according
to their geographic origin. The seeds may be irregularly rhomboidal, oblong or square in
outline, and yellow, olive-green or yellow-brown to dark brown in colour. The Indian
and Moroccan varieties are quoted on the London Drug Market. They are of
pharmaceutical interest as they contain a number of steroidal sapogenin, particularly
diosgenin, which is contained in the oily embryo 11. Fazli and Hardman investigated a
number of commercial samples of seed as possible commercial sources of diosgenin
and reported contents of 0.8-2.2% expressed on a moisture-free basis.
3.5 Solanum species: This large genus (over 1000 spp.) is noted for the production of
C27 steroidal alkaloids in many species. Some of these alkaloids are the nitrogen
analogues of the C 27 sapogenins (e.g. solasodine and diosgenin). Another series of C27,
compounds contain a tertiary nitrogen in a condensed ring system (e.g. solanidine). These
compounds can also be employed in the partial synthesis of steroidal drugs, and a
number of companies have devoted considerable attention to commercial production.
Species so exploited are Solanum laciniatum, S. khasianum and S. aviculare; trials on the
production of S. marginatum have been conducted in South America.
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3.6 Soya bean sterols: The soya (soy, soja) plant, Glyrine max (G. soya) (Leguminosae)
is extensively cultivated for its seeds, which are rich in oil and protein. The seeds also
contain appreciable quantities of the phytosterols, stigmasterol and sitosterol. Although
not sapogenins, they are included here because they are now used extensively for
steroid synthesis. They are obtained as by products of soap-making, being components of
the unsaponifiable matter of the fixed oil. Pure stigmasterol, with its unsaturated sidechain is unable to chemical conversion to suitable starting material and can replace
diosgenin, but it was more recently than sitosterol, the saturated side chain of which
could not be removed chemically without fragmentation.
3.7 Sarsaparilla root: Sarsaparilla consist of the dried roots and rhizomes of species of
smilex( Liliaceae and Smilaceae ). Much chemical work
3.8 Ginseng: The roots of the Panax ginseng (Araliaceae) have hold on the place
Chinese medicine. It is produced in a China, Korea, and Siberia, and considerable
quantity, derived from Panax quinquefolium . Panax quinquefolium (American ginseng
root) Ginseng that is produced in the United States and Canada is particularly prized in
Chinese societies and many ginseng packages are prominently colored red, white and
blue12-22.
Wild ginseng
Red ginseng
14
Ginseng alternatives
and
designated
according
to
their Rf values in
a
system.
particular
The
panaxosides are
termed
panaxoside A, B,
C etc.
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16
17
Unlike the steroidal saponins, the pentacyclic triterpenoid saponins are rare in
monocotyledons. They are abundant in many dicotyledonous families, particularly the
Caryophyllaceae, Sapindaceae, PolygaIaceae and Sapotaceae. Among the many other
dicotyledonous families in which they have been found are the Phytolaccaceae,
Chenopodiaceae, Ranunculaeeae, Berberidaceae, Papaveraceae, Linaceae, Rutaceae.
Zygophyllaceae, Mynaceae, Cucurbitaceac, Araliaceac, Umbelliferae. Primulaceae,
Oleaceae, Lobeliaceae, Campanulaceae, Rubiaceae and Compositae.
In these saponins the sapogenin is attached to a chain of sugar or uronic acid
units, or both, often in the 3-position, as in the examples above.
4.1 Biosynthesis: As with the steroids, involves ring-closure of squalene and is
illustrated in Figure.
Triterpenoid saponins may be classified into three groups represented by amyrin, -amyrin and lupeol, The related triterpenoid acids are formed from these by
replacement of a methyl group by a carboxyl group in positions 4, 17 or 20.
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Genin
Aescigenin
Sugar components
2 glucose, 1 glucoronic acid,
Aralin
Calendula-
Aralidin
Oleanolic acid
tiglic acid
hippocastanum
2 arabinose, 1 glucuronic acid Aralia japonica
2 glucose, 1 galactose,
Calendula
Glycyrrhetinic acid
Noroleanolic acid
1 glucoronic acid
2 Glucoronic acid
1 Rhamnose, 1 glucose,
officinals
Glycyrrhiza spp.
Guaiacum spp.
Hederagenin
1 arabinose
1 glucose, 1 arabinose
saponin A
Glycyrrinic acid
Guaianin
Hederacoside A
Occurrence
Aesculus
Symphytoxide
Hedergenin
1 Arabinose, 2 glucose
Araliaceae
Symphytum
Primula saponin
Quillaliac acid
1 rhamnose, 1 glucose,
officinale roots
Primula spp.
Saikosaponin
Saikogenin F
A.
Quillaia Bark: Quillaia bark (Soap Bark, Panama Wood, Quillaia) is the dried
inner bark of Quillalia saponarica and of other species of Quillalia (Rosaceae). 23,
24
19
Liquorice root: Liquorice consists of the dried unpeeled roots and stolen of the
Glycerrhiza glabra (Leguminosae). Liquorice owes most its sweet taste to
glycyrrhizinic, potassium and calcium salt of the glycyrryzinic acid is the
diglucopyranosiduronic acid of glycyrrhizinic acid which have a triterpenoid
structure. Other hydroxyl and deoxy triterpenoids acids related to glycyrrhetic
acid have been isolated; the C-20 epimer of glycyrrhetic acid is named liquiritic
acid. The other constituents of it are liquiritin, isoliquiritin, liquiritigenin,
isoliquiritigenin. Spanish spp. contain 5-10%, Russian spp. contain 10%, Persian
spp. contain 7.5% of glycyrrhizin. 26
20
D.
22
23
triterpenoid retains all of the regio- and stereochemical features necessary for
continued cyclization. The isolation of these bicyclic triterpenoids supports the
postulation of van Tamelen and his co workers that the cyclization of squalene
precedes via a series of discrete conformationally rigid carbocationic intermediates. 4552, 56
monocyclic
and
new
carbocation followed by a 1, 3-hydride shift from C-17 to C-21. A series of 1, 2shifts and elimination of a proton from C-7. 91
12. Pfaffanes: Pfaffic acid, a novel hexacyclic nortriterpene possessing the pfaffane
skeleton was isolated from Pfaffia paniculata and its structure was established by X-ray
crystallographic analysis of its methyl ester. Subsequently, four new pfaffane-type
nortriterpenes were isolated from P. pulrerulenta together with pfaffic acid and its -Dglucuronopyranoside. 92
27
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29
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31
32
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