STEREOCHEMISTRY CHIRALITY A A

C C D D B B C C Chirality - Stereoisomers

2 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 Biomolecules are Chiral

H OH ‣ Carbohydrates / Sugars H O Glucose HO HO OH H OH H H ‣ DNA

‣ Amino Acids / Proteins O

H2N OH R

4 Chirality in Smell and Taste ‣ Mirror image molecules (enantiomers) interact with chiral receptors in our nose differently.

O O

(R)-(-)-Carvone (S)-(+)-Carvone (R)-(+)-Limonene (S)-(-)-Limonene spearmint oil caraway seed oil orange citrus turpentine/Lemon

5 Chiral Molecules in Enzymes

Me O N

O NH O

HO O H N O H

6 The Case of Thalidomide

O O stereogenic stereogenic carbon N carbon N

* O * O O N O O N O H (R)-thalidomide H (S)-thalidomide beneficial sedative causes birth defects

7 Tartaric Acid ‣ 1849 - Louis Pasteur separated mirror image crystals of sodium ammonium tartrate. OH O OH O HO OH O * Na * * O NH4 O OH * O OH

8 Louis Pasteur

“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 the left; and 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.”

9 Optical Activity ‣ Enantiomers have identical physical properties ‣ mp, bp, spectroscopic, absorptions, etc. ‣ BUT they are different when interacting with plane-polarized light light travels in when the polarized Note that the waves but light passes enantiomer will oscillates in all Light is polarized through a chiral bend the light in the three dimensions and oscillates in a sample, it is bent opposite direction along the path of single dimension out of the original travel plane

chiral chiral sample sample enantiomer polarizing filter

10 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

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

11 Racemates

“...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.” ‣ Racemic Mixture - 50/50 mixture of enantiomers. Shows NO optical activity. light travels in when the polarized Note that the waves but light passes enantiomer will oscillates in all Light is polarized through a chiral bend the light in the three dimensions and oscillates in a sample, it is bent opposite direction along the path of single dimension out of the original travel plane

chiral chiral sample sample enantiomer polarizing filter

12 CIP Rules for R & S Configuration ‣ Rectus - Right, Sinister - Left 1 1 4 Cl Cl 4 H H

3 2 2 3 (R)-2-chlorobutane (S)-2-chlorobutane

13 R & S Configuration

NH2 HO

OH sphingosine

NH2

HO S R R

OH

14 R & S Configuration

O

S S OH H2N OH N CH3 H O alanine proline

15 R & S Configuration OH

HO R O S glucose S S R HO OH OH

16 Diastereomers ‣ Diastereomers - stereoisomers that are not mirror images

STEREOISOMERS

DIASTEREOMERS ENANTIOMERS

17 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.

18 configurational Diastereomers ENANTIOMERS

O O OH HO HO S R OH

HO S R OH OH HO O O

O OH HO S

DIASTEREOMERS HO R DIASTEREOMERS OH O 19 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.

O O OH HO HO S R OH

HO R S OH OH HO O O

IDENTICAL 20 ISOMERS

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

Constitutional Stereoisomers (bonded differently) (Only different in 3-dimensional arrangement)

Enantiomers Diastereomers (mirror images) (not mirror images)

Configurational cis/trans

21