stereochemistry

1. STEREOCHEMISTRY
Presented by
• Tahmina kabir(PHA-17001)
• Arifur Rahman(PHA-17002)
• Noorjahan Hossain(PHA-17003)
• Mustak Ahmed(PHA-17004)
• Md. Yamin Emu(PHA-17006)
Presented to
• Dr. Md. Ashraf Ali ,
Associate professor , Department
of pharmacy , MBSTU.

2. Content
• Definition of Isomerism
• Classification of Isomerism
• Stereoisomerism and Classification
• Conformation analysis
• Conformation of open chain and cyclic compound
• Configuration
• Difference between configuration and conformation
• Chirality of molecules
• Asymmetric synthesis
• Optical resolution
• Stereo selective and stereo specific
• Pharmaceutical importance of stereochemistry

3. Stereochemistry
• Chemistry of space
• Spatial arrangement of atoms and group
Isomer and Isomerism
• The same molecular formula but differ in structural formulas
• This phenomenon is called isomerism

4. Classification of isomerism
Mainly isomerism are two types-
• Structural isomerism
• Stereoisomerism
Structural Isomerism:
• The same molecular formula but different structural formula.
Classification:
It can be classified into following types-
1. a) Chain isomerism: Due to different arrangements of
carbon atoms in a chain

5. b)Ring chain isomerism : Due to different arrangement of carbon chain
present in ring
2)Positional Isomerism: Due to different positions of a substituent or functional
group

6. 3) Functional isomerism: Due to different functional groups.
4)Metamerism : Due to unequal distribution of carbon atoms
on the either side of the functional group.

7. 5)Tautomerism: In which the isomer exist simultaneous in
dynamic equilibrium with each other

8. 2)Stereoisomerism:
• Having the same structural formulas
•But differ only in the spatial arrangement of atoms or groups.
Classification:
a)Geometric isomerism
b)Optical isomerism
Geometric isomerism:
• Posses the same structural formula containing a double bond
• But differ only due to the arrangement of atoms or groups
• It results form a restriction of rotation about double bond or single bond in cyclic compound.

9. Types of geometric isomerism:
• Cis form
• Trans from
Cis form : Two similar groups are on the same side of the
double bond.
Trans form: Two similar groups are on the opposite side of
the double bond.
Cis form
Trans form

10. Geometric isomerism in cyclic compound:
• This geometric isomerism also shown by ring compounds.

11. (E) and (Z) systems:
• if the two groups with the higher priorities are on the
same side of the double bond ,that is described as the
(Z) isomer.
• If the two groups with higher priorities are on the
opposite sides of the double bond then that is called (E)
isomer.

12. Optical isomerism:
Only due to presence of at least one asymmetric carbon atom and the same
compound rotate differently towards plane polarised light.
optical activity – when a substance rotates the plane of plane polarized light.
(1815 by Biot)
plane polarized light – light that has been passed through a nicol prism or
other polarizing medium so that all of the vibrations are in the same plane.
non-polarized polarized

15. Forms of Conformation:
Two forms of conformation:
1) Eclipsed conformation : All hydrogen form atom nearest
to each other.
2)Staggered form : All hydrogen atoms are furthest apart.
They are represented by:
• Sawhorse projection: Visualizes the conformation of a
chemical bond both front and back carbon.
• Newman projection: Visualizes the conformation of a
chemical bond form front to back.

16. Example

17. The Conformational isomers of n- butane
:
s :
Here four conformational isomers are possible:
Two eclipsed conformational isomers
a)Fully eclipsed :less stable
b)Eclipsed :more stable
Two staggered conformational isomer
a)Skew conformational :less stable
b)Trans conformational : more stable

24. CONFIGURATION
Configuration is the relative position of the atoms in a molecule that
can be changed exclusively by cleaving & forming new chemical
bonds.
 Configuration isomers are two types-
Geometric
isomer. Optical isomer.

25. THE INFLUENCE OF CONFIGURATION ON ADME
• ABSORPTION
(-) Norgestrel (+) Norgestrel
Absorption ratetwice
than (+) Norgestrel.
Absorption rate half than
(-) Norgestrel.
Less rapidly absorbed
than L- Dopa
More rapidly absorbed
than D- Dopa

26. DISTRIBUTION
Configurational stereo selectivity appears to have little influence on
the transport of stereo-isomers through the circulatory system.
However, it has been shown that some enantiomers preferentially
bind to a specific plasma protein.
Binds with
alpha- acid
glycoprotein
Binds with
human albumin

27. METABOLISM

28. EXCRETION
• A modest stereo selectivity has been reported in the renal excretion
of a few drugs, such as chloroquine, pindolol & terbutaline.
S – Pindolol: Renal clearance is 1.2
folds greater than R – Pindolol.
R – Pindolol: Renal clearance is 1.2
folds Less than S – Pindolol.

29. Difference between conformation and
configuration
Conformation
• It refers to different arrangements
of atoms in a molecule that can
easily interconvert.
• Interconversion is easy and occurs
in single bond.
• They are very flexible.
• They are inseparable.
• They may be represented by
Fischer formula , Horsesaw
formula , newman formula.
Configuration
• It refers to different arrangements
of atoms in a molecule that can not
easily interconvert.
• Interconversion is difficult and
occurs in covalent bond or making
new chemical bond.
• They are less flexible.
• They are separable.
• They may be represented by R and
S system.

30. Chirality of molecule
• Definition: It is a geometric property of some molecules and ions. A
carbon atom which is bonded to four different groups or atoms is
called chiral carbon . A chiral molecules is non superimposable on its
mirror image .This concept is known as chirality.
• Enantiomer : Each of a pair of molecules that are mirror images of
each other.

31. Cont……..
Diastereomers : Optical isomers that are not mirror image to each other.
 Racemic mixture: It is a mixture of equal amounts enantiomers.

32. Cont…..
• Meso compound: A compound that has more than one asymmetric
carbon which is superimposable in its mirror image .
Meso compound

33. The Sequence rules
Cahn, Ingold, Prelog sequence rules:
sequence rule 1: the atom attached to the chiral center with
the highest atomic number = 1, next = 2, etc.
sequence rule 2: if the four atoms attached to the chiral center
are not all different, the sequence is determined at the first
point of difference.
sequence rule 3: If a chain is connected to the same kind of atom twice or
three times, check to see if the atom it is connected to has a greater atomic
number than any of the atoms that the competing chain is connected to.

34. R/S Systems:
1. Using the Cahn, Ingold, Prelog sequence rules, assign
numbers to each of the four groups attached to the chiral
center.
2. Rotate the number 4 group away from you and observe
the sequence 1  2  3 for the remaining groups.
3. If going from 1  2  3 is clockwise, then the
configuration is R (rectus). If the sequence 1  2  3
is counter-clockwise, then the configuration is S
(sinister).

35. Problems
Are the following R or S ?

36. Solutions
1.S: I > Br > F > H. The lowest priority substituent, H, is already going
towards the back. It turns left going from I to Br to F, so it's a S.
2.R: Br > Cl > CH3 > H. You have to switch the H and Br in order to place the H, the
lowest priority, in the back. Then, going from Br to Cl, CH3 is turning to the right,
giving you a R.
3.Neither R or S: This molecule is achiral. Only chiral molecules can be named R or
S.
4.R: OH > CN > CH2NH2 > H. The H, the lowest priority, has to be switched to the
back. Then, going from OH to CN to CH2NH2, you are turning right, giving you a R.
5.(5) S: −COOH−COOH > −CH2OH−CH2OH > C≡CHC≡CH > HH. Then, going
from −COOH−COOH to −CH2OH−CH2OH to −C≡CH−C≡CH you are turning left,
giving you a S configuration.

37. ASYMMETRIC SYNTHESIS
DEFINATION
Process of producing an optical active compound containing an asymmetric carbon
from a symmetric compound .
Preparation of enantiomer by asymmetric synthesis ( synthesis of lactic acid )
=
=
2[H] Hydrolysis
-
+ C10H19OH
O
CH3 - C - COOH +
Pyruvic acid
C10H19OH
methyl alcohol
O
CH3 – C -COOC10H19
methyl pyruvate
CH3 -CHOH-COOC10H19
methyl lactate
CH3
HO - C - H
COOH
lactic acid methyl alcohol

38. Optical resolution method of racemic mixture
 What is optical resolution method ?
The enantiomer of a racemic mixture is separated by the
following method :
1.Mechanical separation : the separation can be done by “
hand picking” with the help of magnifying lens and forceps .
For example , Sodium ammonium tartarate
LIMITATION :
 Very few enantiomeric substance exist in the form of
mechanically separable crystal
 Time consuming
 Only for solid substances

39. 2.Biochemical separation : this method involves the use of
microorganism for bringing about resolution .
For example ,penicillium glaucum in sodium tartarate
 LIMITATION :
One half of the material is destroying during separation
Process is very slow
Small amount of material can be separated
3.CHEMICAL SEPARATION : Diastereomer can be easily separated
through functional crystallization or distillation .the separated
diastereomer may be converted to optically active compound .
For example ,( +_) lactic acid when treated with L brucine will give
two diasteriomers .

40. Stereo-selective and Stereospecific reaction
Stereo-selective:
A reaction in which a single reactant forms an unequal mixture of
stereoisomers.
Two or more products may be formed.
If products are enantiomers , the reaction is enantioselective.
If they are diastereoisomers , then it is diastereoselective.

41. Stereospecific reaction
A reaction may be stereo specific , if stereo chemically different
materials give stereo chemically different products. For example, the
addition of carbene to cis and trans but-2-ene is a cis addition . Thus
the addition is stereo specific that is, each geometrical isomer forms
one product , cis isomer gives cis-product and trans isomer gives trans
product .
• All stereospecific reactions are necessarily stereoselective ,but all
stereoselective reactions are not stereospecific.

42. Pharmaceutical importance of
stereochemistry
To determining the properties and reactions of organic compound (e.g
spearmint )
Properties of many drugs depends on stereochemistry e.g s-ketamine
(anesthetic )
Todistinguish the enzyme between stereoisomers
The isomers can help in understanding the mechanism behind the adverse
effect and drug action
Toimprove specific action of the drug
Topharmacokinetic and pharmacodynamics properties
Structural element of membrane
Toensure the use of optically pure starting materials (alkaloid, steroids)

43. THANK YOUALL