Stereochemistry

1. Stereochemistry
(A physicochemical property
of drugs)

2. “ Chemistry that studies properties of
stereoisomers”
Or
“The way in which drug is oriented in space”
Physiological properties of a drug are governed
to a great extent by it stereochemistry.
Even optical isomers of a drug can have
different physiological effect.

3.  Isomers that have same molecular formula
and connectivity but differ in a way that
atoms are oriented in space – i.e; Difference
between isomers lies only in 3 D
arrangements of atoms .

4. i) Optical isomerism
ii) Geometrical isomerism

6. “Optical isomerism of drugs is very common ,
many drugs molecules only contain one or
two chiral centers”

7.  Chirality is define as
“ When a compound has no
symmetry ab0ut a particular carbon atom ,
the carbon is said to be as chiral carbon “

8.  Chiral center arises when a carbon atom has
four structurally different groups attach to it.
 When a compound contain one or more
chiral center it is able to rotate plane
polarized light to the right (+) or the left (-)
 E.g; Adrenaline can exist as two enantiomers
that are mirror images of each others and
thus known as non-superimposable

10.  Adrenaline enantiomers have identical
,physical and chemical properties , the only
difference in their properties is that the
enantiomers rotate plane polarize light in
opposite direction , both enantiomers have
different biological properties
 The negative enantiomer exert stronger
effect i.e; Heart rate increases

11.  Device which is used to determine the
direction in which a molecule rotate plane
polarize light is polarimeter.
 X-ray crystallography of adrenaline
enantiomers shown that negative form has R
configuration and the positive form has S
configuration

12. “ Isomers that differ in their spatial
arrangements about a double bond “
Relatively uncommon
Zimeldine antidepressant drug is example
of geometrical isomer

13.  The mixture containing equals amount of
dextro and levo enantiomers of any drug
known as racemic mixture , this mixture will
not rotate plain polarize light
 Physical separation of isomers in any mixture
as pure form is technically difficult.
 Therefore , many of these drugs are used in
form of racemates. For instance , Synthetic
drugs where chiral centers are part of their
structure likeThallidomide

14. “Two compounds that are nonsuperimposable
mirror image of each other “
They have chiral carbon atom.
Have same physical properties.
Both can rotate PPL

15.  d / l are used to donate (+) & (-) respectively .
 D /L are used to donate (R) & ( S)
respectively.

16.  Enantiomers are distinguish only when
placed in a chiral enviornment.
 All methods of separation are based in this
principle
 EE ( enantiomers excess)
 EE% = 100% x ( Xa-Xb)
Where Xa & Xb correspond to mole fraction of
enantiomers

17.  Where more than one chiral center is present
in a molecule there is the possibility of
diastereoenantiomers e.g; captoprill ,
labetalol
 The number of diastereoisomers arising from
n chiral centered is 2n-1

18.  Chromatographic methods : Labetalol two peaks
could be seen in chromatographic trace
 The commercial drug is administer as a mixture of
four isomers
 BP monograph for labetalol checks the ratio of two
chromatographic peaks produce by the two
enantiomeric pairs of diastereoisomers , in order to
saperate enantiomeric pair a chiral chromatographic
coloum would be required and separation on a chiral
coloum produces four peaks , an example a pair of
diastereoisomers used separately as drug is
betamethasone and dexamethsones

19.  These terms refer to relative orientation of
two substituents .
 For instance , In betamethasone Hydroxyl
group at 17 and methyl group 18 are trans (at
opposite side of ring )
 In Dexamethasone Hydroxyl group 18 and
methyl group 17 are cis ( on the same side of
ring)

20.  It is describe as quality control check oblige
parameter in the monograph ofTimolol
maleate ,Tobramycin and phenyl ephrine
HCL.

27.  David G –Waston Physiochemical Aspects of
Drugs
 Chemistry of chiral center
 Organic Chemistry – B.S Bahl