terpenoids · finally, the structure of retene is confirmed by its synthesis (haworth et. al.,...
TRANSCRIPT
Terpenoids
Dr. Vandna Thakur
Assistant Professor
Deptt of Chemistry
HRMMV
Abeitic Acid Tricyclic diterpenoid
Chief constituent of rosin or colophony (steam distillation of
resin of Pine trees gives volatile essential oil (Terpentine oil
(source of alpha-pinene) and non-volarile substance, rosin)
Isolation: Rosin is first boiled in alcoholic soln containing HCl
and AA is obtained as Diamylamine salt.
Molecular formula: C20H30O2
Constiution:
On hydrogenation, AA gives tetrahydro abietic acid which
ensures the p/o 2 double bonds
Gives effervescences with NaHCO3 showing p/o carboxylic acid
group which does esterify easily confirming it to be 3o
carboxylic group.
➢ Herein parent HC is C19H34 (CnH2n-4) which corresponds to tricyclic
Compound
➢ AA dehydrogenates in p/o S/Se/Pd-charcoal by oxidative degradation
To give aromatic HC, retene (1-methyl-7-isopropylphenanthrene)
Degradation of Retene
(All the reaction can only be
explained by considering (I)
as the structure of retene)
To establish the position of isopropyl group:
➢ Fusing (III) with KOH followed by oxidation to give biphenyl
4-carboxylic acid (indicationg isopropyl group in retene is at position 7)
Finally, the structure of retene is confirmed by its synthesis (Haworth et. Al., (1932)
Formation of retene from AA suggests that it has retene carbon skeleton
The position of18 C has been established by retene formation, but for the exact
Structure, we must know:
➢ Position of 3o carboxylic group
➢ Position of angular methyl group
➢ Position of two double bonds
➢ Position of 3o carboxylic group:
➢ Ruzika et. al. ascertained the position of Carboxylic group by following
reactions:
The structure of Homoretene was confirmed by the chemical synthesis
(Haworth, 1932)
Homoretene on oxidation with Alkaline potassium ferricyanide gives
phenanthrene 1,7-dicarboxylic acid
Whereas, oxidation of retene also gives the same product.
Homoretene is 1-ethyl-7-iso propyl phenanthrene.
The position of ethyl group suggests that methyl and carboxyl groups are
Present on Same C (C1) in AA.
Position of angular methyl group:
Confirmed by oxidation and dehydrogenation reactions of AA.
The following reaction establish the structure of reduced AA.
Both, m-xylene and Hemimellitene have a m-methyl group, hence the angular
Methyl group must be in m-position to C1 methyl group.
Position of the double bonds:
❖ Ruzika et. al. showed that AA forms an adduct with maleic anhydride
At above 100 oC indicating the two bonds are in conjugation.
❖ Also AA shows a maximum at 238 nm in the UV region which indicates
Heteroannular conjugation i.e. the bonds are in different rings.
❖ Ring A does not contain a double bond as confirmed by oxidative study on
AA. (Slide no. 7) by Ruzika et al because p/o double bond would have
led to Rupturing of ring A. double bonds are present in ring B and C
❖ The oxidation of AA with acidic KMnO4 gives isobutyric acid which indicates
that Double bonds are present b/w C7-C8 and C13-C14.
On the basis of all the points dicussed, AA is assigned the structure
(Stereochemistry is also studied having following absolute
configuration)
On heating in p/o Pd-Charcoal (250-275 oC), AA gives Dehydroabeitic Acid
which was synthesized by Stork and Schulenberg (1956).
Reactions of Abeitic Acid: mainly Isomerization and
disproportionation occurs.
Isomerization
Disproportionation
Santonin
➢ A sesquiterpenoid lactone
➢ Found in Artemesia species
➢ Medicinal use as anthelmintic (to expel intestinal worms)
Structure:❑ Molecular formula: C15H18O3
❑ Santonin (I) dissolves in alkali to form Santoninic acid (II): this ascertain that
It is a lactone (IR studies support it to be a γ-lactone)
❑ Catalytic hydrogenation Shows the p/o two double bonds
❑ UV absorption shows it to be a a,b-unsaturated ketone (Lambda= 236 nm)
❑ Its reaction with Zn dust gives 1,4-dimethylnaphthalene, propene and
small amount of 1,4-dimethyl-2-naphthol (which suggests the p/o
Naphthalene skeleton.
❑ Reduction of santonin oxime gives santon-amine (III) which on reaction
With HNO2 gives hyposantonin (IV).
All the above reaction can be explained if we accept the structure of
santonin as (I)
Structure elucidation of Hyposantonin (IV):
❑ Hyposantonoin on oxidation with KMnO4 gives 3,6-dimethyl phthalic
Acid (V).
❑ On heating with ethanolic hydrochloride, mixture of two isometic acids
(dihydrosantinic acid (VI). Which on further heating with Ba(OH)2 gives
Product (VII).
❑ (I) and (VI) on oxidation with I2/AcOH gives Santinic Acid (vIII) which also
gives (VII) on heating with Ba(OH)2.
Other reactions of Santonin
Natural α and β-santonin has been synthesized as following
(Abe et al, 1956)
Michael addition is stereospecific, malonic ester group in XVIII takes
More stable equatorial position, following decarboxylation gives XX
( two racemic acids, alpha and Beta). After separating the two acids,
Alpha acids give alpha (+/-) santonin after oxidation and lactonization
Stereochemistry of Santonin:
α-Santonin has the following absolute configuration
β-santonin (Which also occur naturally) is the C11 epimer
Biological role (volatile and non volatile):
- Flavour, fragrance, scent
- Antibiotics
- Hormones
- Membrane lipids
- Insect attractants
- Insect antifeedants
- Mediate the electron transport processes
(in respiration and photosynthesis)
Terpenoids Biological role
Chemical and physical properties
Volatile liquids with no color
keep in amber bottles with minimum air
Odor
Asymmetric centers, isomers with optical activity
only one isomer occurs naturally
Refractive index normally high
is a means to characterize the oil
Miscible in water and soluble in organic solvents
more soluble if contains –OH fatty acids
Reasonably heat stable
can be steam distilled
Tend to be used as solvents for resins
Basic unit
•Thermal decomposition of terpenoids give isoprene as one of the
product.
•Otto Wallach pointed that terpenoids can be built up of isoprene
unit.
•Isoprene rule states that terpenoids are constructed from two or
more isoprene unit.
•Ingold suggested that isoprene units are joined in the terpenoid
via ‘head to tail’ fashion.
•Special isoprene rule states that the terpenoids are constructed of
two or more isoprene units joined in a ‘head to tail’ fashion.
But this rule can only be used as guiding principle and not as a fixed rule.
For example carotenoids are joined tail to tail at their central and there are also some
terpenoids whose carbon content is not a multiple of five.
Isoprene rule
Isoprene is the common name for 2-methylbuta-1,3-diene
CH2CHC
CH3
H2C1 2 3 4
head tail
IsopreneIsoprene unit C5
HeadTail
HeadTail
Isoprene units can be linked:
➢ Usually, head to tail to
form linear terpenes
➢ Head to head
➢ Tail to tail
➢ Cyclic terpenes also
contain links which are
called crosslinks
Head to Head
Isoprene rule linkage
Head to Tail Tail to Tail
β-Carotene
RetinolLimoneneMyrcene
In most naturally occurring terpenes, there are no head to head or tail to tail links eg.
Does not obey the isoprene rule is called an irregular terpene eg.
Cyclic terpenes also contain links that are neither of three, which are called crosslinks
Classification of TerpenoidsGeneral formula : (C5H8)n.
Classified on the basis of value of number of carbon atoms (n) present in the structure.
S.No. No. of carbons Value of n Class
1 10 2 Monoterpenoids (C10H16)
2 15 3 Sesquiterpenoids (C15H24)
3 20 4 Diterpenoids (C20H32)
4 25 5 Sesterpenoids (C25H40)
5 30 6 Triterpenoids (C30H48)
6 40 8 Tetraterpenoids (C40H64)
7 >40 >8 Polyterpenoids (C5H8)n
Biosynthesis
Formation of a chemical compound by a living
organism. It describes the experimental studies carried
out in vivo for the mode of formation of natural
products.
Biogenesis: It describes the various hypothetical
schemes proposed for the formation of natural
products.
Biogenetic Isoprene rule: The mode of arrangement of
C5 units in terpenoids differ to large extent. It has been
shown that each group of terpenoids has its own
isoprene rule, instead of Isoprene units, they are
derived from its simple hypothetical precursors such as
geraniol, farnesol, geranylgeraniol, squalene etc.
Biosynthesis of terpenoids
As discussed earlier, isoprene is precursor of all the terpenoids, but it
Was never found to be present in natural sources. Hence, the hypothesis
is not valid.
It is divided into three parts:
1). Biosynthesis of C5 units
2). Arrangement of these units to form acyclic terpenoids
3). Cyclization of Acyclic terpenoids to cyclic terpenoids
Biosynthesis of C5 units:
1) Synthesis of Mevalonic Acid:
Acetate (C2) molecule is basic precursor of terpenoids. The acetate
Is converted by CoA to active acetate or acetyl-CoA which is then
converted to mevalonic Acid (MVA) (Merck et al, 1956).
Mevalonic acid pathway
❑Formation of (S)-3-hydroxyl-3-methylglutaryl co-enzyme A (HMG-Co A)
by the condensation of acetyl co-enzyme A with acetoacetyl co-enzyme CoA.
❑Enzymatic reduction of (S)-3-hydroxyl-3-methylglutaryl co-enzyme A
(HMG-Co A) with hydrogen from nicotinamide adenine dinucleotide
phosphate (2 × NADPH) to give (R)-mevalonic acid.
Mevalonic acid pathway❑Mevalonic acid undergoes two successive phosphorylation by
adenosine triphosphate (2 × ATP) to give the 5-pyrophosphate.
❑This undergoes a trans-elimination of the tertiary hydroxyl group and
the carboxyl group to form 3-methylbut-3-enyl pyrophosphate
(isopentenyl pyrophosphate, IPP). This is in equilibrium with
dimethylallyl pyrophosphate (DMAPP).
The biosynthesis of MVA from Leucine (M. J. Moon (1946):
To support MVA as an intermediate in Terpenoid biosynthesis:
CoA Dehydrogenation
Supporting Facts for MVA pathway:
❖ MVA has been isolated from natural resources (Wolf, 1957)
❖ Introduction of 14C –labelled MVA in plants; 14C labelled Alpha-pinene
and rubber have been isolated.
❖ Use of 14C labelled acetate gave labelled Citronellal according to Acetate-MVA
Pathway.
GPP (through NPP) serves as the precursor for acyclic terpenoids
GPP serves as the precursor for monocyclic terpenoids via its Cis isomer
(*Mechanism of ring closure are not certain)
Thank you