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)

CONSTITUTIONAL (STRUCTURAL) ISOMERISM (these isomers have different connectivity of bonds)

STEREOISOMERISM (stereoisomers have the same connectivity but differ only in the arrangement of atoms in space)

CONFORMATIONAL STEREOISOMERISM (these are stereoisomers obtained by rotation about sigma bonds; in principle readily interconvertible)

CIS-TRANS STEREOISOMERISM (for alkenes 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

OH

O

O

O CH3

CO2H

CH3

H3C

CH3

O

O Cl

Cl

Cl

Cl

Competing Drugs in the Market

VIOXX (Merck)(now withdrawn)

CELEBREX (Pfizer)

VIAGRA (Pfizer) CIALIS (Eli Lilly)

O

CH3SO2

O

NN

CH3

CF3

SH2N O

O

N

NS

NH

NN

N

O

H3C CH3O

CH3

CH3

OO

OO

N

N

NH

O

O

HCH3

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 )

(+)-morphine?

(+)-cocaine?

(dl)-cocaine? or()-cocaine?

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

Assigning Configuration (R or S)

S configuration

(left turn = S)

(Cahn-Ingold-Prelog Rules)

2-Butanol Configuration Stereoisomers

Is this R or S?*

assign priorities

(right turn = R)

More Examples

Additional Rules for Multiple Bonded Substituents

Cyclic Compounds

enantiomers (not inconvertible)

enantiomers (not inconvertible)

Me

Me

Me

Me

enantiomers (inconvertible by chair flip! WHY?)

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

(flip chair)

identical

Conformational Enantiomers (inconvertible by chair flip!)

Me

Me

Configuration vs Conformational Isomerism

R

SThis 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.

You’ll need to think

this one through

tonight!

Fischer ProjectionsThese can also

be tricky!(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 contains both left- and right-handed isomers in equal amounts. One enantiomer is effective against morning sickness. The other is teratogen (causes birth defects).

Thalidomide Babies (1950’s and 1960’s)

The two enantiomers of thalidomide

N

O

O

NHO

O N

O

O

NHO

O

The Sex Life of the Olive Fruit Fly(Bacrocera Oleae)

O

O

oleane(sex phermone of the olive fruit fly)

O

O

O

O

this enantiomer attracts the males

this enantiomer attracts the females

Vicks Vapor Inhaler (sold in USA)

Active ingredient (R)-(-)-methamphetamine (nasal decongestant).It is the enantiomer of the addictive psychostimulant, (S)-(+)-methamphetamine

NHCH3

H CH3

CH3NH

HH3C

R S