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Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Diastereomers D or L

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Page 1: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

Chapter 15: Chirality

Chiral Stereoisomers Chiral Stereoisomers

EnantiomersR or S

EnantiomersR or S

DiastereomersD or L

DiastereomersD or L

Page 2: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

Chapter 15: Chirality

Objects that are nonsuperposable on their mirror images are chiralchiral (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

stereocenterstereocenter.

Page 3: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

Chapter 15: Chirality

Enantiomers:Enantiomers: Nonsuperposable mirror images.• As an example of a molecule that exists as a pair of enantiomers,

consider 2-butanol.

OH

CH3C CH2CH3

H

HO

CCH3

HCH3CH2

Original molecule Mirror image

Page 4: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

Chapter 15: Chirality

• To summarize;• Objects that are nonsuperposable on their mirror images are

chiralchiral (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 stereocenterstereocenter.

• Objects that are superposable on their mirror images are achiralachiral (without chirality).

• Nonsuperposable mirror images are called enantiomersenantiomers. • Enantiomers always come in pairs.

Page 5: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

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.

• The R,S system is a way to distinguish between enantiomers without having to draw them and point to one or the other.

COOH

H CH3

HOOC

H3C H

The active enantiomerThe inactive enantiomer

Page 6: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

Chapter 15: Chirality

-OH-NH2

-CHO

-CH2OH

-CH2CH3

-CH2H-H

-SH

-COHO

-CH2NH2

-CNH2

O

-I-Br

-Cl

Atom orGroup

oxygen (8)nitrogen (7)

carbon to oxygen, oxygen, then hydrogen (6 —> 8, 8, 1)carbon to oxygen (6 —> 8)

carbon to carbon (6 —> 6)carbon to hydrogen (6 —> 1)hydrogen (1)

sulfur (16)

Reason for Priority: First Point of Difference(Atomic numbers)

carbon to oxygen, oxygen, then oxygen (6 —> 8, 8, 8)

carbon to nitrogen (6 —> 7)

carbon to oxygen, oxygen, then nitrogen (6 —> 8, 8, 7)

bromine (35)

chlorine (17)

iodine (53)

Step 1:Order groups by

Priority.

Higher Atomicnumber

=Higher Priority

Page 7: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

Chapter 15: Chirality

Example:Example: Assign priorities to the groups in each set.

-CH2OH -CH2CH2OH-CH2CH2OH -CH2NH2(a) (b)and and

-CH2OH -CH2CH2COH

O

-CH2NH2 -CH2COH

O

and(c) (d)and

Page 8: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

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

3

14

Page 9: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

Chapter 15: Chirality

Step 3:Follow the three groups projecting toward you in order from highest (1) to lowest (3) priority.

2

3

14

Steering Right = R configuration Steering Left = S configuration

2

1

34

SR

Page 10: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

Chapter 15: Chirality

Example:Example: Assign an R or S configuration to each stereocenter.

OH

CH3C CH2CH3

H

H3C COOHC

HH2N

(a)

(b)

2-Butanol

Alanine

Page 11: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

Chapter 15: Chirality

For a molecule with nn stereocenters, the maximum number of possible stereoisomers is 22nn.• 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:Diastereomers: Stereoisomers that are not mirror images. (N>=2)

Page 12: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

Chapter 15: Chirality

Example:Example: Mark all stereocenters in each molecule and tell how many stereoisomers are possible for each.

CH3

CH3

OH

OH

CH2=CHCHCH2CH3

OH

NH2

OHHO

HO

COOH

NH2

OH

NH2

OH

O

(a) (b) (c)

(d) (e) (f)

Page 13: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

Chapter 15: Chirality

• Ordinary light:Ordinary light: Light waves vibrating in all planes perpendicular to its direction of propagation.

• Plane-polarized light:Plane-polarized light: Light waves vibrating only in parallel planes.

• Polarimeter:Polarimeter: An instrument for measuring the ability of a compound to rotate the plane of plane-polarized light (See next slide).

• Optically active:Optically active: Showing that a compound is capable rotating the plane of plane-polarized light.

Page 14: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

Chapter 15: Chirality

Figure 15.6 Schematic diagram of a polarimeter with its sample tube containing a solution of an optically active compound.

Page 15: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

Chapter 15: Chirality

• Dextrorotatory:Dextrorotatory: Clockwise rotation of the plane of plane-polarized light. Indicated by (+ or D).

• Levorotatory:Levorotatory: Counterclockwise rotation of the plane of plane-polarized light. Indicated by (- or L).

• Specific rotation:Specific rotation: The observed rotation of an optically active substance at a concentration of 1 g/mL in a sample tube 10 cm long.

DD

H3CC

OHH

COOH

CH3

C

HOH

COOH

[]21 = -2.6°= +2.6°21

[]

(R)-(-)-Lactatic acid(S)-(+)-Lactic acid

Page 16: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

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.

Page 17: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

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.

Page 18: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

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.

Page 19: Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

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!

HOOC

H3C H

HOOC

H3C H

OCH3(S)-Ibuprofen (S)-Naproxen