stereochemistr y chirality - cook.chem.ndsu.nodak.edu

STEREOCHEMISTRYCHIRALITY

A

CB C

D

A

CBC

D

2

Chirality - Stereoisomers

Chirality

‣ Enantiomers - molecules that are not superimposable on their mirror image.

‣ Molecules that can exist as enantiomers are called Chiral Molecules.

‣ Molecules that have a plane of symmetry are not chiral (achiral).

‣ Stereogenic Carbons are those that have four different groups attached.

3

4

‣ Carbohydrates / Sugars

‣ DNA

‣ Amino Acids / Proteins

Biomolecules are Chiral

OH

HO

H

HO

H

HOHH OH

OH

Glucose

H2NO

OHR

Chirality in Smell and Taste

‣ Mirror image molecules (enantiomers) interact with chiral receptors in our nose differently.

5

O

(R)-(-)-Carvone (S)-(+)-Carvonespearmint oil caraway seed oil

O

(R)-(+)-Limonene (S)-(-)-Limoneneorange citrus turpentine/Lemon

6

Chiral Molecules in Enzymes

O

ONH

N

O

O

NOH

H

Me

HO

The Case of Thalidomide

7

NH

O O

N

O

O

*stereogeniccarbon

(R)-thalidomidebeneficial sedative

NH

O O

N

O

O

*stereogeniccarbon

(S)-thalidomidecauses birth defects

Tartaric Acid

‣ 1849 - Louis Pasteur separated mirror image crystals of sodium ammonium tartrate.

8

*HO

O

OH

OHOH

O

* *O

O

OH

OHO

O

*Na NH4

Louis Pasteur

9

“I found...that the tartrate was hemihedral..., but strange to say the paratartrate was hemihedral also. Only the hemihedral faces which in the tartrate were all turned the same way, were, in the paratartrates inclined sometimes to the right and sometimes to the left.... I carefully separated the crystals that were hemihedral to the right from those hemihedral to the left, and examined their solutions separately in the polarizing apparatus. I then saw with no less surprise than pleasure that the crystals hemihedral to the right deviated the plane of polarization to the right, and that those hemihedral to the left deviated it to theleft; and when I took an equal weight ofeach of the two kinds of crystals, themixed solution was indifferent towardsthe light in consequence of theneutralization of the two equal andopposite individual deviations.”

Optical Activity

‣ Enantiomers have identical physical properties

‣ mp, bp, spectroscopic, absorptions, etc.

‣ BUT they are different when interacting with plane-polarized light

10

light travels in waves but oscillates in all three dimensions along the path of travel

polarizing filter

Light is polarized and oscillates in a single dimension

chiralsample

when the polarized light passes through a chiral sample, it is bent out of the original plane

chiralsampleenantiomer

Note that the enantiomer will bend the light in the opposite direction

Optical Activity

‣ Amount of rotation depends on how many molecules the light interacts with.

‣ Light at 589 nm (Sodium D line)

‣ Standardized for unit cell and concentration

11

observed rotation (°)cell length (dm) x conc. (g/mL)[α]D =

Racemates

‣ Racemic Mixture - 50/50 mixture of enantiomers. Shows NO optical activity.

12

“...when I took an equal weight of each of the two kinds of crystals, the mixed solution was indifferent towards the light in consequence of the neutralization of the two equal and opposite individual deviations.”

light travels in waves but oscillates in all three dimensions along the path of travel

polarizing filter

Light is polarized and oscillates in a single dimension

chiralsample

when the polarized light passes through a chiral sample, it is bent out of the original plane

chiralsampleenantiomer

Note that the enantiomer will bend the light in the opposite direction

13

CIP Rules for R & S Configuration

Cl Cl

(R)-2-chlorobutane (S)-2-chlorobutane

1

23

H H41

2 3

4

‣ Rectus - Right, Sinister - Left

14

R & S Configuration

HONH2

OH sphingosine

HO RNH2

OH

S R

15

R & S Configuration

H2N

CH3

O

OHNH O

OH

alanine proline

S S

16

R & S Configuration

glucoseO

HO

HO

OHOH

OH

SR

SR

S

17

Diastereomers

‣ Diastereomers - stereoisomers that are not mirror images

STEREOISOMERS

DIASTEREOMERS ENANTIOMERS

18

cis/trans Diastereomers

‣ Although not optically active (not chiral), cis/trans isomers are a form of diastereomer. They differ only in their arrangement in 3-dimensions but are not mirror images.

19

configurational Diastereomers

OH

OH

O

HO

O

HO

HO

HO

O

OH

O

OH

ENANTIOMERS

S R

S R

DIASTEREOMERSDIASTEREOMERS

OH

OH

O

HO

O

HOS

R

20

MESO compounds

‣ Meso Compounds are molecules that contain stereogenic carbons, but are not chiral. Their mirror images are identical. This occurs when there is a plane of symmetry in the molecule.

OH

OH

O

HO

O

HO

HO

HO

O

OH

O

OH

S R

SR

IDENTICAL

21

ISOMERS

ISOMERS(same number and kind of atoms, but are different molecules)

Constitutional(bonded differently)

Stereoisomers(Only different in 3-dimensional arrangement)

Enantiomers(mirror images)

Diastereomers(not mirror images)

Configurational cis/trans