Pharmaceutical Sciences

PHARMACEUTICAL SCIENCES

Subject : Pharmaceutical Sciences

(For Under Graduate Students)

Paper No. : B. Pharm VIIIst Sem

Paper – 38
Herbal Drug Technology

Topic No. & Title : 447:

Chemical and Spectral Approaches to
simple Molecules of Natural Origin,
Concepts of Stereoisomerism taking
examples of Natural Products

Academic Script

ISOMERISM: STRUCTURAL AND STEREOISOMERISM

Isomerism is the phenomenon whereby certain compounds, with the same molecular
formula, exist in different forms owing to their different organizations of atoms. The
concept of isomerism illustrates the fundamental importance of molecular structure
and shape in chemistry. Compounds which showed isomerism are called as “Isomers”.
They are either Structural isomers or Sterioisomer.

No. of isomers of any compound depends upon the number of asymmetric carbon
atom present (Carbon molecule is bonded to four different atoms, Chiral carbon),
which is given by formula (2)n, where n is the no. of asymmetric carbon atom.
Example: If Molecule has 1 chiral carbon= total no. of isomers will be (2)1 =2
If Molecule has 2 chiral carbon= total no. of isomers will be (2)2= 4
If Molecule has 2 chiral carbon= total no. of isomers will be (2)3= 8

Isomerism is of two types: Structural Isomerism and Stereoisomerism

01. Structural Isomerism: Structural Isomers have different structural formula because
their atoms are linked together in different ways. It is arises owing due to
a) Arrangement of Carbon skeleton: showed difference in the arrangement of
atoms.
Example: The formula C4H10 represents two possible structural formulae, butane
and methylpropane.
1
Pharmaceutical Sciences

b) Position of Functional group: have same functional group at different position

Example: Propan-1-ol and propan-2-ol

c) Different Functional groups: have same molecular formula but different

functional groups.
Example: The molecular formula C2H6O represents both ethanol and
methoxymethane.

02. Stereoisomerism
Stereoisomers are isomeric molecules that have the same molecular formula and
sequence of covalently bonded atoms (constitution), but they differ in the three-
dimensional orientations of their atoms in space. They have different spatial
arrangements and their molecules are not superimposable.
There are two types:

2
Pharmaceutical Sciences

a) Geometrical Isomerism
i. Geometric isomerism is also known as cis-trans isomerism or E-Z isomerism or
configurational isomerism. These isomers occur where you have restricted
rotation somewhere in a molecule. They are not superimposable.
ii. Geometrical Isomers involved a double bond, usually C=C, that does not allow free
rotation about the double bond (unlike a C-C single bond).
iii. If priority group attached with different carbon atoms are on the same side of the
molecule, are designates as Cis isomers or Z isomers, while if priority group exist
on opposite sides are called Trans isomers or E isomers.
iv. Stereoisomers may possess quite different physical properties, such as melting
point, density and solubility in water. Ring structures and other steric factors also
result in geometric isomerism
Example: Cis-but-2-ene and Trans-but-2-ene

b) Optical Isomerism
i. Optical isomers are referred to as enantiomers. They involve an atom, usually
carbon, bonded to four different atoms or groups of atoms. They exist in pairs, in
which one isomer is the mirror image of the other.
ii. The central carbon atom to which four different atoms or groups are attached, is
called an asymmetrical carbon atom.
iii. Enantiomers have identical physical constants, such as melting points and boiling
points, but are said to be optically active since they can be distinguished from
each other by their ability to rotate the plane of polarised light in opposite
directions. A mixture of enantiomers in equal proportions is optically inactive, and
is called a racemic mixture.
iv. In nature, most biological compounds, such as amino acids, occur as single
enantiomers. As a result, different enantiomers of a compound may have
substantially different biological effects.
v. When a molecule has more than one source of asymmetry, two optical isomers
may be neither perfect reflection of each other nor superimposeable: some but
not all stereocenters are inverted. These molecules are diastereomers, not
enantiomers. Diastereomers seldom have the same physical properties.

3
Pharmaceutical Sciences

TYPES OF STEREOISOMERS
Dear students, you have completely understood the phenomena of isomerism. Now we
will study about different types of Stereoisomers.
01. Conformational Isomers: They are also called as conformers or rotamers and
produced by rotation of carbon-carbon sigma bonds. They are rapidly
interconvertible into each other at room temperature, therefore cannot isolate.
Example, Staggered and eclipsed form of ethane which arises due to C2-C3 sigma
bond rotation.

02. Configurational Isomers

Cannot arise due to rotation of carbon- carbon sigma bond, therefore can be isolated
easily. They can be classified again in two types.
a. Enantiomers: also known as optical isomers. An enantiomers is one of are two
stereoisomers that are mirror images of each other and are non-
superimposable.
i. Two compounds that are enantiomers of each other have the same
physical properties, except for the direction in which they rotate
polarized light.
ii. Term R and S- refers to the configuration of chirality center while (+) and
(−) sign refers to the direction of plant of polarized light rotates. If they
rotate the plan polarized light towards left side, levoroatory (l) or (-)
sign is used while if they rotate the plan polarized light towards right
side, dextroroatory (d) or (+) sign is used.
Example: Alanine

4
Pharmaceutical Sciences

iii) In nature, only one enantiomer of most chiral biological compounds, such as
amino acids (except glycine, which is achiral), is present.
03. Diastereomers: They are not mirror images of each other.
a) These include meso compounds, cis–trans (E-Z) isomers, and non-
enantiomericoptical isomers.

b) Diastereomers seldom have the same physical properties.

Example: The meso form of tartaric acid forms a diastereomeric pair with both
levo and dextro tartaric acids, which form an enantiomeric pair.

5
Pharmaceutical Sciences

Difference between Diastereomers and Enantiomers:

6
Pharmaceutical Sciences

NATURAL PRODUCTS HAVE STEREOISOMERISM

A wide variety of natural molecule, showed steroisomerism.
1. Menthol: Menthol is a monocyclic monterpenoid alcohol. It has three chiral carbon
centers. So it produces four racemic modification and eight optically active isomers,
those are
 (+), (-)- Menthol
 (+), (-)- Isomenthol
 (+), (-)- Neomenthol
 (+), (-)- Neoisomenthol
(+) – Menthol has a little cooling effect with sweet minty, while (-)- Menthol is very
cooling, fresh sweet minty . It has a taste threshold of 400ppb and a cooling
threshold of 800ppb.

2. Quinine and Quinidine

Both are the quinoline type of alkaloids, obtained from dried bark of Cinchona
officinalis, belonging to the family Rubiaceae. They contain one asymmetric carbon
atom so exsist in two optically active forms.
(-) Quinine: It is levorotatory in nature and produces antimalerial effects, while
(+) Quinidine: It is dextrororatory in nature and produces antiarrthymic effects.

7
Pharmaceutical Sciences

3. Citral: is a mixture of terpenoids with the molecular formula C10H16O. The two
compounds are double bond isomers, due to arrangement of aldehyde group. The
Trans or E-isomer is known as geranial or citral A while Cis or Z-isomer is known as
Neral or Citral B. They are differ from each other in boiling points, Citral A (geraniol)
has a boiling point of 118-1190C while Citral B (Neral) has a boiling point of 117-
1180C.

4. Ephedrine:
It is an alkaloid with a phenethylamine skeleton found in various plants in the genus
Ephedra (family Ephedraceae). Ephedrine exhibits optical isomerism and has two
chiral centers, giving rise to four stereoisomers. The pair of enantiomers with the
stereochemistry (1R, 2S) and (1S, 2R) is designated ephedrine, while the pair of
enantiomers with the stereochemistry (1R,2R) and (1S,2S) is called pseudoephedrine.

8
Pharmaceutical Sciences

Relative pressure activity of D (–)-ephedrine is found to be 36 with regard to its D(+)-

ephedrine isomer at 11 i.e., the former is almost 3½ times more active than the
latter.

5. Limonene:
Limonene is a colorless liquid hydrocarbon classified as a cyclic terpene present in
orange fruits.
It has one chiral carbon, so exist in two enantiomers form i.e. (+) and (-) Limonene.
(+) Limonene: It has fresh citrus orange like odor and a odor threshold is found to be
200ppb.,
while (-) Limonene: has turpentine or lemon like odor threshold is found to be
200ppb., while

9
Pharmaceutical Sciences

6. Carvone:
Carvone is a member of mon-terpenoids, found naturally in many essential oils, but is
most abundant in the oils from seeds of caraway (Carum carvi) and spearmint
(Mentha spicata). It has one asymmetric carbon atom so exist in two optically active
form i.e. S(+)-Carvone and R-(-)-Carvone.
 S-(+)-Carvone is also used to prevent premature sprouting of potatoes during
storage, being marketed in the Netherlands for this purpose.
 (R)-(–)-Carvone has been proposed for use as a mosquito repellent.

7. Tartaric Acid: Tartaric acid is a white crystalline organic acid that occurs naturally in
many plants, most notably in grapes. It has 2 asymmetric carbon atoms and exist in
three forms
D (+)- Tarteric acid and L (-)- Tarteric acid both has melting point at 174 C while, Meso
Tartaric acid has melting point at 148 C.

10
Pharmaceutical Sciences

Some other naturally occurring compounds those who are showed stereoisomer’s
are Citronellol, Pinene, Campor and Piperine, Ergotamine etc.

CONCLUSION
Dear students, you have studied in detail about common phenomena of isomerim
occurs in different molecules along with that you have students in detail about
Stereoisomer’s including enantiomers and Diasteromers. From different examples of
naturally occurring herbal drug molecule, you have clearly understand that even isomers
have same molecular or structural formula, but differ in the arrangement of atoms in
space leads to variation in their pharmacological activities like quinine and Quinidine.
Knowledge about steriochemisty also helps in drug designing. Now a day by synthetic
modification, steroselective drug molecules are prepared.
With all these information here we come to end of today's lecture. Do keep in mind
what we discussed today. Time for you to self-study.

11