5. STEREOISOMERISM. (approx. lecture time: 5 hr)
Topics covered: 5.1-5.16.
Left and Right hands are not
the same (not superimposable)
There are also “Left” and “Right”
handed molecules and they are also
not the same (not superimposable)
The study of “handedness” of organic molecules (configurational
stereoisomerism) is essential for understanding their structure and
function in biology
ISOMERISM
(isomers have the same molecular
formula but differ in structure)
STEREOISOMERISM
(stereoisomers have the same
connectivity but differ only in
the arrangement of atoms in
space)
CONSTITUTIONAL
(STRUCTURAL) ISOMERISM
(these isomers have different
connectivity of bonds)
CIS-TRANS
STEREOISOMERISM (for alkenes
CONFORMATIONAL
STEREOISOMERISM
(these are stereoisomers
obtained by rotation about
sigma bonds; in principle
readily interconvertible)
and cyclic compounds: stereoisomers
that differ in location of atoms on
different sides or faces)
CONFIGURATIONAL STEREOISOMERISM
(stereoisomers obtained by different relative arrangement of 4
bonds on an sp3 hybridized carbon; not interconvertible;
maximum number = 2n ; n = number of chirality centers)
Configurational Stereoisomerism
chirality centre
(if W,X,Y,Z are
not the same)
not superimposable
not superimposable
(chirality centre = stereogenic centre = chiral centre = chiral carbon)
Recognizing Chirality Centers
Competing Drugs in the Market
VIOXX (Merck)
(now withdrawn)
VIAGRA (Pfizer)
CELEBREX (Pfizer)
CIALIS (Eli Lilly)
CONFIGURATION STEREOISOMERISM
is “independent” of
CONFORMATIONAL STEREOISOMERISM
Conformational stereoisomers are rapidly interconverting.
Configurational stereoisomers DO NOT readily interconvert.
(When studying configurational stereoisomerism, we choose a
particular “representative” conformational structure, but
realizing that many others also exist)
Notes on Configurational Stereoisomerism
A chiral molecule is one that is not superimposable onto its mirror image structure. The
pair of structures are called enantiomers (“left” and “right” hand molecules).
Enantiomers have identical physical properties except for the rotation of plane polarized
light.
Maximum number of configuration stereoisomers possible = 2n (where n is the number of
chirality centers in the molecule). There may be less due to the existence of meso
compounds.
A meso compound is an achiral compound that has 2 or more chirality centers. It is
achiral because these compounds have a plane (or center) of symmetry.
Diastereomers are stereoisomers that are not enantiomers. This is a widely used term
that is not restricted to configurational stereoisomerism. Diastereomers have different
chemical and physical properties!
A racemic mixture is a 1:1 ratio of the (two) enantiomers. Racemization (to racemize)
is the process of converting a solution of one pure enantiomer towards a racemic
mixture.
Configurational enantiomers and diastereomers are not readily interconvertible.
Optical Activity
Specific Rotations [a]D
(+) rotation “dextrorotatory (d )
(-) rotation “levorotatory (l )
Compound
[a]D
Compound
[a]D
Acetic acid
0
Cholesterol
-31.5
Chloroform
0
Morphine
-132
Sucrose
+66.5
Cocaine
-16
Camphor
+44.3
Methamphetamine
+16
(+)-morphine?
(+)-cocaine?
(dl)-cocaine?
or
()-cocaine?
Assigning Configuration (R or S)
S configuration
(Cahn-Ingold-Prelog Rules)
2-Butanol Configuration Stereoisomers
assign
priorities
*
Is this R or S?
More Examples
Additional Rules for Multiple Bonded Substituents
Cyclic Compounds
enantiomers (not inconvertible)
enantiomers (not inconvertible)
enantiomers (inconvertible by chair flip! WHY?)
Configuration vs Conformational Isomerism
R
S
This is a meso compound
when considered FLAT
But we know it exists in chair forms. The two chair forms are
non-superimposable mirror images and are conformational
enantiomers, and rapidly interconvertible, unlike configurational
stereoisomers.
Conformational Enantiomers (inconvertible by chair flip!)
Fischer Projections
(How to draw and manipulate molecules with two
or more contiguous chirality centres quickly)
R
R
R
S
S
S
Interchange any 2 substituents on same carbon results in its INVERSION
Rotating molecule by 180 degrees generates the SAME STRUCTURE
Rotating molecule by 90 degrees is FORBIDDEN
The Aldoteroses
(The simple 4-carbon sugars)
Thalidomide Babies (1950’s and 1960’s)
Thalidomide contains both left- and right-handed isomers in equal
amounts. One enantiomer is effective against morning sickness. The
other is teratogen (causes birth defects).
The two enantiomers of thalidomide
The Sex Life of the Olive Fruit Fly
(Bacrocera Oleae)
Vicks Vapor Inhaler (sold in USA)
Active ingredient
(R)-(-)-methamphetamine (nasal
decongestant).
It is the enantiomer of the addictive
psychostimulant, (S)-(+)-methamphetamine
R
S