Stereokimia

STEREOKIMIA

ENANTIOMER
PROYEKSI
VS EPIMER KONFORMASI
FISHER
DIASTEREOMER

PROYEKSI KIRALITAS DAN

KONFIGURASI
NEWMAN OPTIS AKTIF
Stereostruktur
C4H10
 Geometric Isomers
Cis/Trans isomers in compounds with double
bonds
 Stereoisomers (Optical isomers)

 Enantiomers: nonsuperposable mirror images

 as an example of a molecule that exists as a pair of
enantiomers, consider 2-butanol

chiral
chiral
center
OH HO center

H3 C
C H H C CH
3
CH2 CH3 CH3 CH2
Origin al molecu le Mirror image
 Enantiomers

 one way to see that the mirror image of 2-butanol is not

superposable on the original is to rotate the mirror image

rotate th e
mirror image
OH 180° OH by 180° about OH
C H the C-OH b on d
H3 C H C CH H3 C
C CH CH
2 3
CH2 CH3 3
CH3 CH2 H
Origin al molecu le Mirror image The mirror image
rotated by 180°
 Enantiomers
 now try to fit one molecule on top of the other so that all
groups and bonds match exactly

OH
The mirror image
turn ed by 180° C CH CH
H3 C 2 3
H

OH
The original molecule C H
H3 C
CH2 CH3

 the original and mirror image are not superposable

 they are different molecules with different properties
 they are enantiomers (nonsuperposable mirror images)
 Enantiomers
 Objects that are not superposable 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

chiral center

 Enantiomers are optical active compounds.

Stereoisomers (Conformation of acyclic compounds)
Stereoisomers (Conformation of cyclic compounds)
Stereoisomers (Conformation of cyclic compounds)
Stereoisomers (Conformation of cyclic substituted
compounds)
Stereoisomers (Conformation of cyclic substituted
compounds)
 Configuration of Enantiomers
R,S Convention -> Arrangement of groups around
a chiral atom
Rules for
Priority
 Problem: assign an R or S configuration to each
stereocenter
H
H Cl
(a) (b) OH

O
(c) O
-

NH3 +

CH3 CH3

COOH HOOC

The inactive enan tiomer Th e active enantiomer

of ibup rofen
Beberapa senyawa dipiperamida dari tumbuhan Cabe Jawa
(Piper retrofractum), ( Muharini, 2015)
 Optical Activity
 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

 Optically active: showing that a compound rotates the

plane of plane-polarized light
 Polarimeter

 Schematic diagram of a polarimeter

 Optical Activity
 Dextrorotatory (+): clockwise rotation of the plane of plane-
polarized light

 Levorotatory (-): counterclockwise rotation of the plane of

plane-polarized light

 Specific rotation: the observed rotation of an optically active

substance at a concentration of 1 g/100 mL in a sample tube 10
cm long; for a pure liquid, concentration is in g/mL (density)
COOH COOH
C H H C
H3 C CH3
OH HO
(S)-(+)-Lactic acid (R)-(-)-Lactatic acid
21 21
[] D = +2.6° [] D = -2.6°
 Isomers with several chiral centers

 For a molecule with 1 stereocenter, 21 = 2

stereoisomers are possible

 For a molecule with 2 stereocenters, a maximum of

22 = 4 stereoisomers are possible

 For a molecule with n stereocenters, a maximum of

2n stereoisomers are possible
 Isomers with several chiral centers
O
 2,3,4-Trihydroxybutanal * *
HOCH2 -CH-CH-CH
OH OH

 two stereocenters; 22 = 4 stereoisomers are

possible

CHO CHO CHO CHO

H C OH HO C H H C OH HO C H

H C OH HO C H HO C H H C OH

CH2 OH CH2 OH CH2 OH CH2 OH

A pair of enan tiomers A pair of enantiomers
(Erythrose) (Threose)
Enantiomers & Diastereomers
 Meso Compounds
 Meso compound: an achiral compound possessing two or more stereocenters
 tartaric acid
 two stereocenters; 2n = 4, but only three stereoisomers exist

COOH COOH COOH COOH

H C OH HO C H H C OH HO C H

H C OH HO C H HO C H H C OH

COOH COOH COOH COOH

A meso compound A pair of enantiomers
(plane of symmetry)
Conformation vs Configuration
 Chirality in the Biological World
 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

 It’s a chiral world!

 Chirality in Biomolecules
 Enzymes (protein bio-catalysts) 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
 Chirality in the Biological World

 Schematic diagram of the surface of an enzyme capable of

distinguishing between enantiomers
 Chirality in Biomolecules
 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, whereas its R enantiomer is inactive
 the S enantiomer of naproxen is the active pain reliever, whereas
its R enantiomer is a liver toxin!

CH3 CH3

HOOC HOOC

OCH3
(S)-Ib uprofen (S)-N aproxen
 Racemic mixture: an equimolar mixture of two
enantiomers

because a racemic mixture contains equal

numbers of dextrorotatory and levorotatory
molecules, its specific activity is zero

 Resolution: the separation of a racemic mixture into

its enantiomers
 Enzymes as resolving agents
H CH3 H3 C H

C OEt Et O C

O + O
H3 CO OCH3
Eth yl e ster of (S)-n aproxen Eth yl es ter of (R)-n aproxen
(not affected by th e este ras e)
1. esteras e N aOH, H 2O
2. HCl, H 2 O
H CH3

OH
C

H3 CO O
(S)-N ap roxe n
 Fischer projection
 Fischer projection: a two dimensional representation for showing
the configuration of a tetrahedral stereocenter.
 It is used mainly for sugars (carbohydrates) and amino acids.
 horizontal lines represent bonds projecting forward
 vertical lines represent bonds projecting to the rear
 the first and last carbons in the chain are written in full;
others are indicated by the crossing of bonds

Carbon with
con vert to highest oxidation
CHO a Fischer CHO state
projection
H C OH H OH
CH2 OH CH2 OH
(R)-Glyceraldeh yd e (R)-Glyceraldeh yd e
 D- and L-Monosaccharides

 In 1891, Emil Fischer made the arbitrary assignments of D- and

L- to the enantiomers of glyceraldehyde

CHO CHO
H OH HO H
CH2 OH CH2 OH
D -Gly ceraldehy de L-Gl yceraldehy de
[]25
D
= +13.5° []25
D
= -13.5°

(R) - Glyceraldehyde (S) - Glyceraldehyde

 Compounds with more chiral centers -
Monosaccharides
 According to the conventions proposed by Fischer
 D-monosaccharide: a monosaccharide that, when written as a
Fischer projection, has the -OH on its penultimate carbon on
the right
 L-monosaccharide: a monosaccharide that, when written as a
Fischer projection, has the -OH on its penultimate carbon on
the left
CHO CHO
CHO CHO H OH H H
H OH HO H H OH H OH
H OH H OH H OH H OH
CH2 OH CH2 OH CH2 OH CH2 OH
D-Erythrose D-Threose D-Ribose 2-Deoxy-D-
ribose
D- and L-Monosaccharides
Cyclic Structure – Hemiacetal Form of Sugars

 Monosaccharides have hydroxyl and carbonyl groups

in the same molecule and exist almost entirely as
five- and six-membered cyclic hemiacetals

anomeric carbon: the hemiacetal carbon of a

cyclic form of a monosaccharide

anomers: monosaccharides that differ in

configuration only at their anomeric carbons
 Haworth Projections
 the anomers of D-glucopyranose

1
CHO red raw to sh ow th e -OH CH2 OH
H OH on carbon-5 close to the
aldeh yd e on carbon-1 H5 OH
HO H H O
OH H C
H OH HO 1 H
5
H OH
H OH
CH2 OH
D -Glucose anomeric anomeric
CH2 OH carbon CH2 OH carb on
O H O
H OH (  ) H
H + H
OH H OH H
HO H HO OH(  )
H OH H OH
-D -Glucopyranose -D -Glucopyranose
(-D -Glucose) ( -D -Glucos e )
 Fischer projection of Amino Acids
 With the exception of glycine, all protein-derived amino acids
have at least one stereocenter (the α-carbon) and are chiral
 the vast majority have L-configuration (natural occurring)

COO- COO-
+
H NH3 H3 N H
CH3 CH3
D -Alanin e L-A lanine