Chapter 15: Chirality
Chiral Stereoisomers
Enantiomers
R or S
Diastereomers
D or L
Chapter 15: Chirality
Objects that are nonsuperposable on their mirror images are chiral
(from the Greek: cheir, hand).
• They show handedness.
The most common cause of enantiomerism in organic molecules is
the presence of a carbon with four different groups bonded to it.
• A carbon with four different groups bonded to it is called a
stereocenter.
Chapter 15: Chirality
Enantiomers: Nonsuperposable mirror images.
• As an example of a molecule that exists as a pair of enantiomers,
consider 2-butanol.
OH
C H
H3 C
CH 2 CH 3
Origin al molecu le
HO
H C CH
3
CH3 CH2
Mirror image
Chapter 15: Chirality
• To summarize;
• Objects that are nonsuperposable on their mirror images are
chiral (they show handedness).
• The most common cause of chirality among organic molecules is
the presence of a carbon with four different groups bonded to
it.
• We call a carbon with four different groups bonded to it a
stereocenter.
• Objects that are superposable on their mirror images are achiral
(without chirality).
• Nonsuperposable mirror images are called enantiomers.
• Enantiomers always come in pairs.
The R,S system
Because enantiomers are different compounds, each must have a
different name.
• Here are the enantiomers of the over-the-counter drug
ibuprofen.
H
CH3
COOH
The inactive enan tiomer
H3 C H
HOOC
Th e active enantiomer
• The R,S system is a way to distinguish between enantiomers
without having to draw them and point to one or the other.
Chapter 15: Chirality
Step 1:
Order groups by
Priority.
Higher Atomic
number
=
Higher Priority
Atom or
Grou p
-I
-Br
-Cl
-SH
-OH
-N H 2
O
-COH
O
-CN H 2
O
-CH
-CH 2OH
-CH 2N H 2
-CH 2CH 3
-CH 2H
-H
Reason for Priority: First Point of D ifferen ce
(Atomic numbers)
iodine (53)
bromin e (35)
ch lorine (17)
su lfu r (16)
oxygen (8)
nitrogen (7)
carbon to oxygen, oxygen, th en oxygen (6 —> 8, 8, 8)
carbon to oxygen, oxygen, th en nitrogen (6 —> 8, 8, 7)
carbon to oxygen, oxygen, th en hydrogen (6 —> 8, 8, 1)
carbon to oxygen (6 —> 8)
carbon to nitrogen (6 —> 7)
carbon to carbon (6 —> 6)
carbon to hydrogen (6 —> 1)
hydrogen (1)
Chapter 15: Chirality
Example: Assign priorities to the groups in each set.
(a) -CH2 OH and -CH2 CH2 OH
O
(c) -CH2 OH and -CH2 CH2 COH
(b) -CH2 CH2 OH and -CH2 NH2
(d ) -CH2 NH2
O
and -CH2 COH
Chapter 15: Chirality
Step 2:
Orient the molecule in space so that the group of lowest priority (4)
is directed away from you. The three groups of higher priority (1-3)
then project toward you.
2
1
4
3
Chapter 15: Chirality
Step 3:
Follow the three groups projecting toward you in order from
highest (1) to lowest (3) priority.
2
R
2
S
3
1
4
4
3
Steering Right = R configuration
1
Steering Left = S configuration
Chapter 15: Chirality
Example: Assign an R or S configuration to each stereocenter.
OH
(a)
C
H
CH2 CH3
2-Bu tanol
H3 C
H2 N H
(b)
C
H3 C
COOH
Alanin e
Chapter 15: Chirality
For a molecule with n stereocenters, the maximum number of
possible stereoisomers is 2n.
• We have already verified that, for a molecule with one
stereocenter, 21 = 2 stereoisomers (one pair of enantiomers) are
possible.
• For a molecule with two stereocenters, a maximum of 22 = 4
stereoisomers (two pair of enantiomers) are possible.
• For a molecule with three stereocenters, a maximum of 23 = 8
stereoisomers (four pairs of enantiomers) are possible, and so
forth.
Diastereomers: Stereoisomers that are not mirror images. (N>=2)
Chapter 15: Chirality
Example: Mark all stereocenters in each molecule and tell how
many stereoisomers are possible for each.
OH
(a) CH2 =CHCHCH2 CH3
HO
(d)
HO
(b)
CH3
CH3
(e)
OH
(c)
NH2
OH
COOH
NH2
OH O
OH
OH
(f)
NH2
Chapter 15: Chirality
• Ordinary light: Light waves vibrating in all planes perpendicular to
its direction of propagation.
• Plane-polarized light: Light waves vibrating only in parallel planes.
• Polarimeter: An instrument for measuring the ability of a compound
to rotate the plane of plane-polarized light (See next slide).
• Optically active: Showing that a compound is capable rotating the
plane of plane-polarized light.
Chapter 15: Chirality
Figure 15.6 Schematic diagram of a polarimeter with its sample
tube containing a solution of an optically active compound.
Chapter 15: Chirality
• Dextrorotatory: Clockwise rotation of the plane of planepolarized light. Indicated by (+ or D).
• Levorotatory: Counterclockwise rotation of the plane of planepolarized light. Indicated by (- or L).
• Specific rotation: The observed rotation of an optically active
substance at a concentration of 1 g/mL in a sample tube 10 cm
long.
COOH
C
H
H3 C
OH
(S)-(+)-Lactic acid
21
[] D
= +2.6°
COOH
H C
CH3
HO
(R)-(-)-Lactatic acid
21
[] D
= -2.6°
Chapter 15: Chirality
Except for inorganic salts and a few low-molecular-weight organic
substances, the molecules in living systems, both plant and animal,
are chiral.
• Although these molecules can exist as a number of
stereoisomers, almost invariably only one stereoisomer is found
in nature.
• Instances do occur in which more than one stereoisomer is
found, but these rarely exist together in the same biological
system.
Chapter 15: Chirality
How an enzyme distinguishes between a molecule and its
enantiomer.
Figure 15.7 A schematic diagram of an enzyme surface that
can interact with (R)-glyceraldehyde at three binding sites but
with (S)-glyceraldehyde at only two of the three sites.
Chapter 15: Chirality
Enzymes (protein biocatalysts) all have many stereocenters.
• An example is chymotrypsin, an enzyme in the intestines of
animals that catalyzes the digestion of proteins.
• Chymotrypsin has 251 stereocenters.
• The maximum number of stereoisomers possible is 2251!
• Only one of these stereoisomers is produced and used by any
given organism.
• Because enzymes are chiral substances, most either produce or
react with only substances that match their stereochemical
requirements.
Chapter 15: Chirality
• Because interactions between molecules in living systems take
place in a chiral environment, a molecule and its enantiomer or
one of its diastereomers elicit different physiological responses.
• As we have seen, (S)-ibuprofen is active as a pain and fever
reliever, while its R enantiomer is inactive.
• The S enantiomer of naproxen is the active pain reliever, but its
R enantiomer is a liver toxin!
H3 C H
HOOC
H3 C H
HOOC
OCH3
(S)-Ib uprofen
(S)-N aproxen