Diastereomers

Diastereomers: compounds that contain two or more chiral centers can exist as more than 2 stereoisomers . The general rule is that the maximal number of stereoisomers is 2n ,where n is the number of chiral centers.
(n=2 ,, 2=4) H.W ,,, EX14.5

Example: 2,3,4-trihydroxybutyraldehyde
HOـــCH2ــC*H ــC*Hـــ CHO
OH OH
2 Chiral carbons . 4 stereoisomers:
CHO CHO CHO CHO HO c H H C OH H C OH HO C H
HO C H H C OH HO C H H C OH
CH2OH CH2OH CH2OH CH2OH
1 2 3 4
Erythrose Threose
1&2 Are mirror images (pair of enantiomers)
3&4 Are mirror images (pair of enantiomers)

Example: 2,3,4-trihydroxybutyraldehyde
HOـــCH2ــC*H ــC*Hـــ CHO
OH OH
2 Chiral carbons . 4 stereoisomers:
CHO CHO CHO CHO HO c H H C OH H C OH HO C H
HO C H H C OH HO C H H C OH
CH2OH CH2OH CH2OH CH2OH
1 2 3 4
Erythrose Threose
1&2 Are mirror images (pair of enantiomers)
3&4 Are mirror images (pair of enantiomers)

1

1
(1&3), (2&4) are not mirror image they are called Diasteroisomers . they differ in their physical properties.

Diastereomers :stereoisomers ,that are Optically active but not mirror images .

Meso stereoisomers : certain molecules that contain two chiral carbon atoms do not exist as four stereoisomers .
Tartaric acid OH (22=4) Isomers
HO2 C CHCH CO2H
OH
Because tartaric acid has two chiral atoms ,four stereoisomers would be expected .However, only three stereo isomers have even been iolated.
CO2H CO2H CO2H CO2H
H C OH HO C H H C OH HO C H
HO C H H C OH H C OH HO C H
CO2H CO2H CO2H CO2H
L-Tartaric acid D-Tartaric acid Identical
1 2 3 4
CO2H CO2H CO2H CO2H
H C OH HO C H H C OH HO C H
HO C H H C OH H C OH HO C H
CO2H CO2H CO2H CO2H
L-Tartaric acid D-Tartaric acid Identical
1 2 3 4


1&2 cannot be superimposed on their mirror images and are one pair of enantiomers.
At first glance ,it appears that another pair of enantiomers ,structures 3&4 can be drawn., However, structures 3&4 are mirror images that can be superimposed and therefore are identical this can be confirmed by rotating structure 3 by 180°degrees in the plane of the page .the result is the same structure as 4:
CO2H CO2H
H C OH HO C H
H C OH Rotate by HO C H
CO2H 180° CO2H
3 Identical to 4
The term meso is given to an isomer that contain chiral atoms but can be superimposed on its mirror image . Because of this ,a meso stereoisomers is optically inactive .Therefore ,there are three stereoisomers of tartaric acid :a meso isomer and a pair of enantiomers ……………………………………………………………………..

The meso stereoisomer then is a compound with chiral centers that can never 3
3
be optically active because it can be superimposed on its mirror images. H.W. EX.14-7 P.372
Resolution of racemic mixture : The process of separating a pair of enantiomers into the pure stereoisomers is called resolution.

Mechanical separation : This method was used by louis Pasteur in 1848 to separate the stereoisomers of a crystalline tartaric acid salt . He noticed that the salts crystallized into 2 forms that were mirror images each other :some were “left_ handed ” crystals and others were "right-handed” crystals .by using a pair of tweezers and a magnifying glass ,he has able to separate the 2kinds of crystals.
Resolution using Diastereomers, Diastereomers have different physical properties. This fact provides us with a method of resolving a racemic mixture. The idea is simple .we react a racemic mixture with an optically active reagent. The product is a mixture of two diastereomers. we then pick one property, such as their solubility in ethyl alcohol that is different for the two diastereomers. we use this property to separate one diastereomer from the other .The separated diastereomers are each reacted to reconvert them to the optically active reagent and the separated enantiomers.
Let us apply this method to the resolution of Benzedrine, a compound that is used an a stimulant
ـــــCH2CHNH2
Benzedrine CH3
The functional group of Benzedrine is an amine group.it is a base & reacts with organic & inorganic acids to form salts .An organic acid can be used that is a pure enantiomer. (read p.373)
**********************
Enzymatic Resolution : this method involves giving a living system a racemic mixture. the system reacts with only one enantiomer and leaves the other one behind.
Chiral compounds and living systems:-
it has been found that a pair of enantiomers will react differently only with chiral reagents.
When they react with achiral reagent, no difference in their chemical reactivity is observed.
Because living systems usually react with only one of a pair of enantiomers, the living system is also chiral. The part of the living system that is chiral is the enzyme .an enzyme has the ability to react with only one of a pair of enantiomers. this ability of an enzyme is called its stereospecificity.
Enzyme stereospecificity : The ability of an enzyme to react with only one of a pair of enantiomers.
The enzyme reacts with a compound , called the substrate ,to form a complex. the enzyme is chiral and therefore forms a complex with only one enantiomer of the substrate. The chemical reaction occurs in the complex. once the reaction has occurred , the complex breaks apart and the enzyme in freed.
This interaction between an enzyme and substrate ,CABZY, in fig.14-10. In this example the enzyme has three binding sites, one specific for A, another for B, and a third for Z .
The binding sites are arranged on the surface an shown in fig.14-10.
……………………………………………………………………………………………..
Y D-enantiomer Z L-enantiomer
C C NO binding
A Z A B Y at this site


A
A
Z
Z

B

Z
Z
B
B
A
A
B
B

Enzyme

Surface with 3 specific
Binding sites
Fig 14-10 stereospecificity of an enzyme
…………………………………………………………
To from an enzyme -substrate complex ,all three sites on the enzyme must bind with the corresponding groups or atoms of the substrate .
Only Dــenantiomer can bind to the surface with all 3 ــgroups attached to the correct binding sites . The Lـenantiomers can bind to a maximum of two sites . In this way ,the enzyme can distinguish between the two enantiomers .
It is simple to explain ,in general terms why the chiral environment of a molecule is so important to its reaction in biological systems.
…………………………………………………………………………………………..
للاطلاع
للاطلاع
Stereochemistry at cyclic systems (steroids)
Mirror
H H H H
OH OH OH OH


Superimposable
cis 1,2-cyclohexanediol
Mirror
OH H H OH
H OH OH H
Not Superimposable
Trans-1,2-cyclohexanediol

Steriods: cholesterol substance deposited on the walls of arteries and as the chief constituent of gallstones ,is the kinds of alcohol called a sterol

للاطلاع

للاطلاع
12 18 R20,etc

Dالنص هنا

Dالنص هنا
c
c
11 13 17
19
19
1 9 16
9
9
8
8
B
B
11
11
A
A


2 1 8 14 15

3 5 7 Coming out of the

4 6 plane of paper
β-bonds
Stereochemistry is indicated by solid lines and dotted lines (α-bonds going behind the plane of paper ).
H
B
B
A
A
9
9

1 C

6
6
10
10
8
8
2 8 H A 3β,6α-diol
4
4
8
8
HO 3 7