Chemistry of Natural Products

Chemistry of
Natural Products
Dr. Mohamed Rabie

Why study natural products
chemistry (Phytochemistry)?
Novel Skeleton and Drug Lead

Availability (Economical Factor)
COOCH3 OCH3
N O OH
O C
Cocaine Guaiacol
(Local anesthetic) (Expectorant)
Green crops anti-feedants
O
Tasmania lanceolata
Humulus lupulus
Structural Characterization of Natural Products
Isolation of Monoterpenoids and Sesquiterpenoids
There are four methods of extraction of the

terpenoids
(i) Chromatography
(ii) Steam distillation
(iii) Extraction by means of volatile solvents
(iv) Adsorption in purified fats
Method (ii) is the one most widely used.
2x400 litre Extraction Plant
How to obtain Molecular formula?
Elemental Analysis: Oxidation (Burning)
High Resolution Mass Spectrum
 Electron Impact (HR-EI-MS)
 Fast Atom Bombardment (HR-FAB-MS)
NMR Spectra for estimating the composition of C and H.
BB Decoupled CMR for all types of carbon signals (1o , 2o , 3o ,
4o )
DEPT-90 for CH (methine);
DEPT-135:
CH/CH3 (methyl) (positive or upward);
CH2 (methylene) (negative or downward)
How to verify Functional Groups?
IR:
carbonyl, amide, ester, substituted phenyl,
hydroxy, amine, alkyl, ether, etc
Optical property
Specific optical rotation: similar skeleton and
conformation
How to identify Chromophores?
Chromophore: UV-VIS spectrum
CH3
Terpenoids H2C C CH=CH2
Terpenoids are
Isoprene
naturally occurring
organic
compounds, mostly
found in plants.
Terpenoids are
structurally related
as they are all
They can be either composed of
hydrocarbons or isoprene units
oxygenated repeated twice or
compounds. more.
Isoprene Rule: All Naturally occurring
terpenoids consist of isoprene units (C5H8)n
connected together in a head-to-tail
arrangement.
CH3
H2C C CH=CH2
Head Tail Head Tail
Isoprene
C C
C C C C C C C C
Isoprene Isoprene
unit unit
Classification of Terpenoids:
Terpenoids are classified according to the
number of isoprene units (C5H8)n into:
1- Monoterpenoids (n=2): C10H16
2- Sesquiterpenoids (n=3): C15H24
3- Diterpenoids (n=4): C20H32
4- Sesterterpenoids (n=5): C25H40
5- Triterpenoids (n=6):
C36H48
6- Tetraterpenoids (n=8):C48H64
(Carotenoids)
7- Polyterpenoids (n is a large number)
(Rubber)
General methods for determining structure
(i) A pure specimen is obtained, and the
molecular formula is determined by means
of mass spectrometry.
(ii) If oxygen is present in the molecule, its
functional nature is determined.
(iii) The presence of olefinic bonds is
determined by means of bromine, and the
number of double bonds is determined by
analysis of the bromide, or by quantitative
hydrogenation.
(iv) Degradative oxidation by ozone, acid,
neutral, or alkaline permanganate and
chromic acid.
(v) Ultraviolet spectroscopy has been used for the
detection of conjugation.
(vi) Infrared Spectroscopy is very valuable for
detecting the presence of a hydroxyl group or
an oxo group
(vii) NMR Spectroscopy has been used to detect
and identify double bonds, to determine the
nature of end groups and also the number of
rings present.
(viii) X-ray analysis is very useful, where
applicable, for elucidating structure and
stereochemistry of terpenoids.
(ix) The final proof of structure depends on
synthesis
Monoterpenoids
Monoterpenoids may be subdivided into three
groups:
Acyclic Monocyclic Bicyclic
Acyclic Monoterpenoids:
These are the monoterpenoids that consist of a
straight chain of carbon atoms with no ring
structures.
Examples: Myrcene, Citral, Ionones and Geraniol
Myrcene
It is obtained from the essential oil from the plants bay,
verbena, myrcia (from which is gets its name) and
others. It can also be synthesized by the pyrolysis of
pinene.
Myrcene is one of the most important chemicals used in
the perfumery industry. Because of its pleasant odor, it
is occasionally used directly. But it is also highly valued
as an intermediate for the preparation of flavor and
fragrance chemicals
α-Myrcene is the name for the structural isomer 2-

methyl-6-methylene-1,7-octadiene which is not found in
nature.
1- Myrcene
1- Molecular formula C10H16
2- Catalytic hydrogenation (platinum) converts myrcene

into a decane C10H22 thus myrcene contains three
double bonds, and is an open-chain compound.
3- Myrcene forms an adduct with maleic anhydride, two

of the double bonds are conjugated (Diels-Alder
reaction).
4-Ozonolysis of myrcene produces acetone,

formaldehyde and a ketodialdehyde, and the latter, on
oxidation with chromic acid, gives succinic acid and
carbon dioxide.
These results can be explained by assigning
structure (I)
CH2
H3C
C=CH-CH2-CH2-C-CH=CH2
H3C 7 6 5 4 3 2 1
8 (I)
IUPAC name: 7-methyl-3-methylene-octa-1,6-diene
It is common to express the structure of myrcene
as:
(II) (III) (IV)

The process of ozonolysis can be represented as
shown:
O
O3 O CO2H
+ CHO CrO3 + CO
2CH2O + 2
CHO CO2H
Ketodialdehyde
This structure for myrcene is supported by the fact

that on hydration (under the influence of sulphuric
acid), myrcene form an alcohol which, on oxidation
gives citral:
H2O (O)
H2SO4 CH2OH CHO
Citral
 Citral, or 3,7-dimethyl-2,6-octadienal or
lemonal, is either of a pair of terpenoids
with the molecular formula C10H16O. The
two compounds are double bond isomers.
The E-isomer is known as geranial or citral
A. The Z-isomer is known as neral or citral
B.
 Citral is therefore an aroma compound

used in perfumery for its citrus effect.
Citral is also used as a flavor and for
fortifying lemon oil. It also has strong anti-
microbial qualities, and pheromonal effects
in insects.
 Citral is present in the oils of several

plants, including lemon myrtle (90-95%),
Litsea cubeba (70-85%), lemongrass (65-
85%), Lemon verbena (30-35%), lemon
balm, lemon and orange.
2- Citral
1- Molecular formula C10H16O.
2- Citral was shown to contain an oxo group, e.g. it
forms an oxime
3- On heating with potassium hydrogen sulphate,
citral forms p-cymene.
C
C
C C KHSO4
C C
C 
C
C C
p-Cymene
4- Citral is reduced by Na/Hg to an alcohol, geraniol,
C10H18O and is oxidized by Ag2O to geranic acid,
C10H16O2, with no loss of carbon. Thus, the oxo
group in citral is an aldehyde group.
5- Oxidation of citral with alkaline KMnO4 followed by
CrO3 gives acetone, oxalic and laevulic acids. Thus,
if citral has structure (I), the formation of this
oxidation products can be represented as follows:
CHO
i) KMnO4 O CO2H
+ + O
ii) CrO3 CO2H
CO2H
(I)
6- aqueous potassium carbonate converted citral into

6-methylhept-5-en-2-one (II) and acetaldehyde.
Furthermore, methylheptenone itself is also oxidized
to acetone and laevulic acid; this in accord with
structure (I).
CHO
O
K2CO3 CHO (O) O O
+ +
H2 O CH3
CO2H
(I) (II)
The structure of citral is finally proved by synthesis:

Br
O i) Na/liq NH3 HO Zn-Cu HO
+ C2H2 PBr3
ii) H2O H 2O
i) NaEAA
ii) HO-
iii) H+
OH OH
H+
H2 i) BrMgC CMgBr O
+
CHO OEt
Pd/BaSO4 OEt ii) H
(II)
Two Geometrical isomers of citral exist:
CHO H
H CHO
trans- (E-) form cis- (Z-) form

citral-a; geranial citral-b; neral

Chemistry of Natural Products

Uploaded by

Copyright:

Available Formats

Chemistry of Natural Products

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Chemistry of Natural Products

Uploaded by

Copyright:

Available Formats

Chemistry of

Dr. Mohamed Rabie

Novel Skeleton and Drug Lead

There are four methods of extraction of the

α-Myrcene is the name for the structural isomer 2-

2- Catalytic hydrogenation (platinum) converts myrcene

3- Myrcene forms an adduct with maleic anhydride, two

4-Ozonolysis of myrcene produces acetone,

(II) (III) (IV)

This structure for myrcene is supported by the fact

 Citral is therefore an aroma compound

 Citral is present in the oils of several

6- aqueous potassium carbonate converted citral into

The structure of citral is finally proved by synthesis:

trans- (E-) form cis- (Z-) form

You might also like