bài giảng hóa lập thể

8/14/2019 bi ging ha lp th

1/40

S t e r e o c h e m i s t r y :a n in t r od u c t ion

Ch e m 30A F a ll 2002

Gra z ia P i i z z i , S t ev e H a rd in g er


2/40

Stereochemistry of Tetrahedral Carbons

We n eed :

on e Ca rbon sp 3-h ybr id i zed , a t l ea s t

to rep resen t m olecu les a s 3D objec ts

For ex a m p le:

C

Br

H

H

ClC

H

Br

H Cl

C

H

H

Br

Cl

H

H

Br

Cl

2D d r a w in g

Not a p p r o p r ia t e for S t e r e oc h e m

3D d r a w in g

Ap p r op r ia t e for S t e r e o c h e m

2


3/40

Lets consider some molecules

i d e n t i c a l (s a m e co m p ou n d )

Fir st p a i r

S econ d p a i r

Br

HClH

H

ClBrH

A B

F

ClBrH

H

ClBrF

C D

s a m e m o le c u la r fo r m u la (C H 2BrCl )

s a m e a t o m c o n n e c t iv it y

s a m e m o le c u la r fo r m u la (C H F B r C l)

s a m e a t o m c o n n e c t iv it y

s t e r e o i s o m e r s

(t w o d iffe r e n t c om p o u n d s )

s u p e r p o s a b l e

n o n s u p e r p o s a b l e

3


4/40

Thus, we can define

Stereo isomersS tereo isomers: i som er s t h a t h a v e

sa m e for m u la a n d con n ect iv i ty bu t

d i f f er i n t h e p osi t i on of t h e a tom s

i n sp a ce

S tereochemis t ryS tereochemis t ry: ch em ist r y t h a t

s tu d ies th e p roper t ies of stereoisom ers

4


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Historical perspective

Ch r is t ia a n H u yge n s(1629-1695). Du t ch a s t r on om er ,

m a t h e m a t ic ia n , a n d p h ys ic is t .

H e d is co ve r s p la n e p o la r ize dl igh t :

N or m a l lig h t

( n o n p o l a r i z e d )

H o r i zo n t a l l y

p o la r i zed li gh t

D ir ec t i o n o f

l i gh t

H o r i z o n t a lf i l ter V e r t i c a lf i l ter

L i g h t

co m p l e t e l y

b l o ck ed

5


6/40


7/40


J e a n Ba p t is t e Bio t (1774-1862)I n 1815, h e n o t e s t h a t c e r t a in

n a t u r a l o r ga n ic com p ou n d s (liq u id s

o r s olu t i on s ) r o t a t e p la n e p o la r ize dligh t (Op t ica l Ac t ivi ty ).

p l a n e

po la r i z e d

l igh t

t u b e con t a in in ga l iq u id o r g a n ic

com p o u n d or

so lu t ion

p l a n e

po la r i z e d

l igh t

IN OUTm o l ecu l em ole cu

le

mole cu lem o le c u le

m olec

u le

molec

u le

7


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Definitions

Op t ica l ly Ac t iveOp t ica l ly Ac t ive: t h e a b i l i t y of som ecom p ou n d s t o r ot a t e p l a n e p ol a r i z ed l ig h t .

DextrorotatoryDextrorotatory (+)(+): a n op t i ca l ly a ct i ve

com p ou n d t h a t r ot a t es p l a n e p ol a r i z ed l igh t i n a clock w ise d ir ect ion .

LevorotatoryLevorotatory ((--)):: a n op t i ca l ly a ct i vecom p ou n d t h a t r ot a t es p l a n e p ol a r i z ed l ig h t in a cou n t er cl ock w i se d i r ect ion .

N

H

CH3

NCH3

H3C H

(-)-Nicot ine

(+)- M e t h a m p h e t a m i n e

8


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In 1819, R a cem ic Ac id w a sd is co ve r e d . La t e r s h o w n t o h a v e

t h e sa m e for m u la a s T a r t a r ic Acid .

Historical perspectiveHO CO 2H

CO2HHO

In 1832, B io t n o te s t h a t T a r t a r i cAcid fr o m g r a p e ju ic e fe r m e n t a t io n

r ot a t e s p la n e p o la r ize d l ig h t in a

c lock w ise d ir e c t i on :

HO CO 2H

CO2HHO

HO CO 2H

CO2HHO

HO CO 2H

CO2HHO

HO CO 2H

CO2HHO

p l a n e

po l a r i zed

l igh t

t u b e con t a i n in g

s o lu t i on o f

Ta r t a r i c Ac id(TA)

p la n e p o la r ize d lig h t ,

r o t a t e d c lo ck w is e

IN OUT

T A is d e x t r o r o t a t o r y9


10/40

In 1819, R a cem ic Ac id w a sd is co ve r e d . La t e r s h o w n t o h a v e

t h e sa m e for m u la a s T a r t a r ic Acid .

Historical perspectiveHO CO 2H

CO2HHO

In 1838, B io t n o te s t h a t R a c e m i cAcid d o es n o t r o t a t e p la n e

p o la r ize d lig h t :

p l a n e

po l a r i zed

l igh t

t u b e co n t a in in g

s o lu t i on o f

Ra cem ic Ac id

(RA)

p la n e p o la r ize d l ig h t ,

u n c h a n g e d

HO CO 2H

CO2HHO

HO CO 2H

CO2HHO

HO CO 2H

CO2HHO

HO CO 2H

CO2HHO

IN OUT

RA is n o t op t ica lly

a c t i ve10


11/40

I n 1847, h e r e p e a t s e a r lie r w o r k o n

R a cem ic Ac id . Cr ys ta lliza t ion o f

s od iu m a m m on iu m sa lt g ive s m ir r o r

im a g e cr ys t a ls t h a t h e se p a r a t e d b y

h a n d . E q u im o la r s olu t io n s o f s ep a r a t e d

cr ys t a ls h a ve eq u a l b u t op p os it e op t ica l

ac t iv i ty :

Historical perspectiveLou is P a s t e u r (1822-1895)

HO CO 2

CO2HO

Na

NH4

R a c e m ic a c idsa l t

s e p a r a t e

c r y s t a l s

D= +12.7 (+)-Ta r t a r ic Acid(d e x t r or o t a t o r y , n a t u r a l)

[]D= +12.7o

(-)-Ta r t a r ic Acid

(le vo r o t a t or y , u n n a t u r a l)

[]D= -12.7o

11


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I n 1853, P a s t e u r s t u d ie s M e s o t a r t a r i cAcid (sa m e for m u la a s R a c e m ic a n d

T a r t a r ic Ac id ) b u t fa ils t o s e p a r a t e

in t o (+) a n d (-) c r ys t a ls .

I n 1854, h e n o t e s t h a t ce r t a in p la n t

m old m e t a bo lizes (+)-t a r t a r ic a c idbu t n o t (-)-t a r t a r ic a c id .

O CO2H

CO HHO

12

Hi i l i


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J ose p h A.

LeBe l

(1847-1930)

J a cob u s H .

va n t H off (1852-1930)

Ca r b on w i t h 4 a t t a c h m e n t s is T e t r a h e d r a l.

A m ole cu le h a v in g a t e t r a h e d r a l ca r b o n w it h 4d i ffe r e n t a t t a ch m e n t s m a y e xis t a s a p a i r

o f isom er s .

In 1874, t h ey p r op ose :

13


14/40

Therefore..

Stereo isomersS tereo isomers: i som ers t h a t d i f f er on l yi n t h e p osi t ion of a t om s i n sp a ce, a n d t h a t

ca n n ot b e i n t er con v er t ed b y r ot a t i on

a r ou n d a sin g le bon d .

Stereocenter S tereocenter : a ca r bon a t om bea r in g 4

d i f f er en t a t om s or g r ou p of a t om s.F

ClBrH

H

ClBrF

C D

* *C ,D a r e a p a ir o f s t e r e o i s o m e r s

C a r bon * is a s t e r e o c e n t e r

14

th l


15/40

..another example

S t e r e o is om e r s o f 2-c h lo r o b u t a n e

HCl H

Cl

* *

A B

A,B a r e s t e r e o i s o m e r s

Ca r b o n s * a r e s t e r e o c e n t e r s

A,B a r e n o n s u p e r p o sa b le

m ir r or im a g es

E n a n t i o m e r sE n a n t i o m e r s : s t e r e ois om e r s t h a t a r e

n on su p e r p o sa b le m ir r o r im a g es .

C h i r a l: a n y m o le cu le t h a t i s n on s u p e r p os a b lew it h it s m ir r o r im a g e (i .e . A a n d B a r e c h ir a l).

A c h i r a l: a n y m o le cu le t h a t i s n o t c h ir a l.

R a ce m ic m ixt u r e : a 1:1 (eq u im ola r ) m ixt u r e o f t w o e n a n t iom e r s . 15

U l d I


16/40

Unsolved Issues

J ose p h A.

LeBe l(1847-1930)

J a c ob u s H .

va n t H off (1852-1930)

Ca r b on w i t h 4 a t t a c h m e n t s is T e t r a h e d r a l.

A m ole cu le h a v in g a t e t r a h e d r a l ca r b o n w it h 4

d i ffe r e n t a t t a ch m e n t s m a y e xis t a s a p a i r

o f isom er s .

O CO2H

CO HHO

Me so ta r t a r ic Ac idc ou ld n ot b e se p a r a t e d

in to (+) c r ys t a ls a n d

(-) cr yst a ls

16


17/40

N ot lo n g a g o , I e xp r e s se d t h e v ie w t h a t t h e la c k o f g e n e r a le d u ca t i on a n d o f t h r o u g h t r a i n in g in c h e m is t r y w a s on e of t h e

r e a s o n s o f t h e c a u s es of t h e d e t e r io r a t io n o f c h e m ic a l r e se a r c h

in G e r m a n y ..Will a n y on e t o w h o m m y w o r r ie s se e m e x a g g er a t e d

p le a s e r e a d , i f h e c a n , a r e c e n t m e m o ir b y a H e r r v a n t H o ff o nT h e Ar r a n g em e n t o f At o m s in S p a c e , a d o c u m e n t c r a m m e d t o

t h e h ilt w it h t h e o u t p o u r in g of c h ild is h fa n t a s yT h is Dr . J . H .

van t H off, em p loyed b y t h e Ve t e r in a r y C ollege a t U t r ech t , h a s ,

s o i t s e e m s , n o t a s t e fo r a c cu r a t e c h e m ic a l r e s e a r c h . H e fin d s it

m o r e c on v en ie n t t o m o u n t h is P e ga s u s (e vid e n t ly t a k e n fr om t h e

s t a b le s o f t h e Ve t e r in a r y Co lle g e ) a n d t o a n n o u n c e h o w , o n h is

b o ld flig h t t o Mo u n t P a r n a s su s , h e sa w t h e a t o m s a r r a n g ed in

in s pa ce .

In 1901 va n t Hoff r ece ived t h e fi r s t Nobe l P r i ze in

C h e m i s t r y .

In 1877, H e r m a n n Ko lbe , on e o f t h e be s t o r ga n ic

ch e m is t of t h e t im e w r ot e :

In 1877, H e r m a n n Ko lbe17

T k h bl


18/40

Take-home problem

S t e r e o i s o m e r so f 2-c h lo r obu ta n e

H Cl HCl

* *

AB

E n a n t i o m e r s

E n a n t i o m e r s: s t e r e ois om e r s t h a t a r e

n on su p e r p o sa b le m ir r or im a g es .

R a ce m ic m ixt u r e : a 1:1 (eq u im ola r ) m ixt u r e o f

t w o e n a n t iom e r s .

Remember :Remember:

Ex p la in w h y:Ex p la in w h y:

A a n d B ca n n ot b e p h ys ica lly se p a r a t e d .

a r a c e m ic m i xt u r e of A a n d B h a s n o op t ica la c t i vit y (n o r o t a t i on o f p la n e p o la r ize d ligh t ).18

S


19/40

Summary

StereoisomersS tereo isomers: i som er s t h a t h a ve sa m e for m u la

a n d con n ect i vi t y b u t d i f f er in t h e p osi t ion of t h e

a tom s in spa ce. T h ey p ossess on e or m ore

stereocenters .

S tereocenter S tereocenter : a ca rbon a tom bea r in g 4 d i f feren t

a tom s or g rou p of a t om s.

C h i r a lC h i r a l: a n y m ol ecu l e t h a t i s n on su p er p osa b le

w i th i t s m i r ror i m a ge.

Enan t iome rsEnan t iome rs: s tereoisom ers t h a t a re n on

su perp osa b le m i r ror im a ges.

R a cem i c m ix t u r eR a cem i c m ix t u r e : a 1:1 (equ im ola r ) m ix tu r e of

t w o en a n t i om er s.

Op t ica l ly Ac t iveOp t ica l ly Ac t ive: th e a b il i t y of som e

com pou n d s t o rota t e p la n e pola r i zed l igh t .19

C fi ti f St t


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Configuration of Stereocenters

H Cl HCl

* *

A B

Th e C a h n -In gold -P r e log (C IP )

r u le a s s ig n s R or S

co n figu r a t ion t o t h e t w o

e n a n t i o m e r s .

E n a n t io m e r s of 2-c h lo r o b u t a n e :

1) As sig n t h e p r io r i t i es t o t h e gr o u p s a t t a c h e d t o

t h e s t e r e oce n t e r . P r ior i t y is b a s e d on t h e a t om icn u m b e r , i .e . H h a s low e r p r io r i t y t h a n Cl.

Bu t m e t h y l a n d e t h yl b ot h a r e a t t a c h e d t o t h e

s t e r e oce n t e r t h r ou g h c a r b o n ! I n t h e se ca s e s,

p r ior it y a s s ign m e n t s p r oc ee d o u t w a r d , t o t h e n e x t

a t o m s . T h e M e t h y l ca r b on h a s 3 H s a t t a c h e d w h ile

t h e E t h y l ca r b on h a s 2H s a n d a n d a ca r b on (t h e

t e r m in a l m e t h y l g r o u p ). T h e r e fo r e , t h e la t t e r g e t sh igh e r p r ior i t y . 20

C fi ti f St t


21/40


H Cl

*

A

4 1

32 2) O r ie n t t h e m o le c u le so t h a t t h eg r o u p o f p r io r i t y fo u r (lo w e s t p r io r i t y )

p oin t s a w a y fr om t h e ob s er ve r .

H Cl

*4 1

32 3) Dr a w a c ir cu la r a r r ow fr omt h e gr o u p o f fir s t p r io r i t y t o t h e

g r o u p o f s ec on d p r io r i t y .

4) I f t h is c ir c u la r m o t ion is c lock w ise , t h e

e n a n t iom e r is t h e R e n a n t iom e r . If i t is

c ou n t e r c lo ck w is e , i t is t h e S en a n t iom e r . Th u s ,A i s th e R e n a n t iom e r o f 2-c h lo r obu ta n e .

21R e n a n t iom e r

C fi i f S


22/40


CH3

CH3H

CO2HH3C

CH3

CH3H3C

CO2

H3C

CH3

CH3

CO2H

H

I b u p r o f e n , a na n t i i n f l a m m a t o r y

a g e n t

R e n a n t iom e r

N ot a

S t e r e o c e n t e r !

N o t aS t e r e o c e n t e r !

* *

S e n a n t iom e r

13

4

2

1

2

4

3

22


23/40

Molecules with multiple stereocenters

Molecu les w it h 1 s t e r e oc en t e r

ca n b e R or S

2 p oss ib le


Molecu les w it h n s t e r e o c e n t e r s

c a n h a v e a ll t h e p o ss ib lec om b in a t i on s of R a n d S for

e a c h s t e r e oce n t e r

2n poss ib le


23

Tartaric Acid


24/40

Tartaric AcidHO CO 2H

CO2HHO

*

*

2 s t e r e oc en t e r s 4 p oss ib les t e r e o i s o m e r s

M i r r o r

HO CO 2H

CO2HHO

H

H

S

S

OHHO2C

HO2C OH

H

H

R

R

HO CO 2H

CO2HHO

H

H

R

S

OHHO2C

HO2C OH

S

R

E n a n t i o m e r s D

i

a

s

t

e

r

o

m

e

r

s

D

i

a

st

e

r

om

e

r

s

D ia s

tD ia s t

?

24

Remember


25/40

Remember

E n a n t i o m e r sE n a n t i o m e r s : s t e r e oisom e r s t h a t a r e n onsu p e r p o sa b le m ir r or im a ge s.

D i a s t e r e o m e r sD i a s t e r e o m e r s : s t e r e ois om e r s t h a t a r e n ot: s t e r e ois om e r s t h a t a r e n o t

m ir r or im a ge s.m ir r or im a ge s.F o r e xa m p le :

HO CO 2H

CO2HHO

H

H

S

S

OHHO2C

HO2C OH

H

H

S

Rm i r r o r

i m a g e

n ot m i r r or

i m a g e

(S , S)-Ta r t a r ic a c id (S , R )-Ta r t a r ic a c id

DIASTEREOMERS25


26/40

m i r r o r

i m a g e

HO CO 2H

CO2HHO

H

H

RS

OHHO2C

HO2C OH

SR

m i r r o r

i m a g e


?

26

(R , S)-Ta r t a r ic a c id (S , R )-Ta r t a r ic a c id

Wh t E ti ?


27/40

HO CO 2H

CO2HHO

H

H

R

S

OHHO2C

HO2C OH

S

R

Why not Enantiomers?

E n a n t i o m e r s :

sa m e m ole cu la r for m u la

s a m e c on n e ct iv it y

m ir r or im a g es

n o n s u p e r p o s a b l e

XS u p e r p o s a b l e

Ach ir a l c om p ou n d

S a m ecompound!!!!

27

Wh t E ti ?


28/40

HO CO 2H

CO2HHO

H

H

R

S

OHHO2C

HO2C OH

S

R

Why not Enantiomers?

S a m ecompound!!!!

Me so com p ou n dA com p ou n d w i t h a t le a s t 2 s t e r e oc en t e r st h a t i s a c h i r a l d u e t o t h e p r e se n c e of a p la n e

of s ym m e t r y

28

p la n e of s ym m et r y

Properties of Stereoisomers


29/40

Properties of StereoisomersE n a n t i o m e r sE n a n t i o m e r s : h a ve sa m e ch e m ica l a n d

p h ys ica l p r op e r t ie s in a n a c h i r a l

e n vir on m e n t b u t t h ey d iffe r o n t h e s ign

o f r o t a t io n o f p la n e p o la r ize d lig h t .F o r e xa m p le : E n a n t iom e r s of E p in e p h r in e (Ad r e n a l in e )

OH

OH

HOH

N

C 3

HH

HO

O

OHH

N

C 3

HH

RS

S a m e m e lt i n g /b o ilin g p o in t , s a m e r a t e o f r e a c t io n w it hS a m e m e lt i n g /b o ilin g p o in t , s a m e r a t e o f r e a c t io n w it h

a c h ir a l r e a g en t s , s a m e d e g r e e of r o t a t io n o f p la n ea c h i r a l r e a g en t s , s a m e d e g r e e of r o t a t io n o f p la n e

p o la r ize d ligh tth u s d iffic u lt t o s e p a r a t e !p o la r ize d ligh tth u s d iffic u lt t o s e p a r a t e !

[]D

= - 53.3o[]D

= + 53.3o

29



30/40


C a r v on e e xis t s a s

a p a i r o f e n a n t iom e r s :

O

H

O

H

(+)-carvone ( - ) -carvone

s m e lls lik e c a r a w a y s m e lls lik e s p e a r m in t

S R

[]]]]D = + 62.5 []= + 62.5 []= + 62.5 []= + 62.5 []D==== 62.562.562.562.5Note: N o r e la t i on s h ip e x is t s b e t w e e n t h e S /R c o n fig u r a t i on

a n d t h e s ign or t h e m a g n it u d e o f r o t a t io n o f p la n e

p o la r ized lig h t . A 1:1 m ix t u r e o f en a n t i om er s (r a c e m i c m ixt u r e ) h a s

a lw a y s n o op t i ca l a c t i vit y (r o t a t io n e q u a l t o ze r o)

b e c a u s e t h e r o t a t io n o f 50% o f o n e e n a n t i om e r is

c a n c e lle d o u t b y t h e r o t a t io n (e q u a l b u t o p p o sit e ) o f 50% o f t h e o t h e r e n a n t i om e r . 30



31/40


D i a s t e r e o m e r sD i a s t e r e o m e r s : h a v e d iffe r e n t c h e m ic a l

a n d p h ys ica l p r op e r t ie s in a n y t yp e of

e n v i r o n m e n t .

HO CO 2H

CO2HHO

S

S

OHHO2C

HO2C OH

S

R

(S ,S)-Ta r t a r ic Acid Me sot a r t a r ic Acid

[]D - 12.7 0 (a ch i r a l)Mel t in g p . (oC) 171-174 146-148

Den si ty (g /cm 3) 1.7598 1.660

So lu b i li t y in H 2O 139 125

31

Biological Significance of Chirality


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Biological Significance of ChiralityS in c e m o st o f t h e n a t u r a l (b i olo gic a l) e n v ir o n m e n t

c on s is t s o f e n a n t i om e r ic m o le cu le s (a m in o a c id s ,

n u cle os id e s, ca r b o h y d r a t e s a n d p h os p h olip i d s a r e

c h ir a l m o le cu le s ), t h e n e n a n t i om e r s w ill d is p la y

d iffe r e n t p r op e r t ie s . Th e n , in ou r b o d y :

D r u g

E n z y m e


Tigh t Bin d in g Wea k Bin d in g

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E n a n t iom e r s of E p in e p h r in e

( - ) -Ep inephr ine(+) -Ep inephr ine

OH

OH

OH

H

N

H3C

H

HOH

OH

H

HO

N

H3C

H

H

R S

Anion ic

s i t e

F la t a r e a

N o t Occu p i ed

Anion ic

s i te

F la t a r e a

O c c u p i e d


E n z y m e

33Poor er Fi t P oor er Fi t L ess A ct i veL ess A ct i ve B et t er Fi t B et t er Fi t Mor e A ct iv eMore A ct iv e

The case of Thalidomide


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N

O

O

N

O

O H

Thalidomidewas synthesized in West Germany in 1953 byChemie Grnenthal. It was marketed (available to patients)

fromOctober 1, 1957 (West Germany) into the early1960's. Sold in at least 46 countries (US not included),Thalidomide was hailed as a "wonder drug" that provided a

"safe, sound sleep". It was a sedative that was found to beeffective when given to pregnant women to combat many ofthe symptoms associated with morning sickness. No clinicaltesting was available to show that Thalidomide molecules couldcross the placental wall affecting the fetus until it was too late.

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N

O

O

N

O

O H

Thalidomidewas a catastrophic drug with tragic side effects.Not only did a percentage of the population experience the

effects of peripheral neuritis, a devastating and sometimesirreversible side effect, but Thalidomide became notoriousas the killer and disabler of thousands of babies. When

Thalidomide was taken during pregnancy (particularly duringa specific window of time in the first trimester), it causedstartling birth malformations, and death to babies. Any partof the fetus that was in development at the time of ingestioncould be affected.

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N

O

O

N

O

O H

*

1 s t e r e o ce n t e r = 2 s t e r e o is om e r s

N

O

O

N

O

O H

H

N

O

O

N

O

O H

H

S-t h a lid om id e R -t h a lid om id e

S R

S e d a t i v e

(t o ca lm n e r v ou s n e s s)

T e r a t o g e n

(t o ca u s e b i r t h d e fe c t s )36

Why did the two enantiomers display


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y p y

different biological activity?

E n a n t i o m e r s d i f f e r i n t h e a r r a n g e m e n t o f a t o m s in s p a c e . T h e r e fo r e , t h e S e n a n t iom e r of

T h a lid o m id e c a n fi t t h e a c t iv e s it e o f a

spec i f ic enzyme ( l ike a key fo r a spec i f iclock ) p r od u c in g t h e d e s ir e d e ffe c t (s e d a t i ve ).

On t h e o t h e r h a n d , t h e R e n a n t i o m e r c a n n o t

i n t e r a c t w i t h t h e s a m e s i t e d u e t o a d i f f e r e n t

a r r a n g e m e n t o f a t o m s ( 3 D s h a p e ) . A s

c o n s e q u e n c e , i t f i t s a d i f f e r e n t e n z y m e a c t i v e

poc ke t t r i gge r ing a d i f f e r e n t b io log i c a l e f f e c t

( toxic) .37

How to solve this problem?


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How to solve this problem?

Chemical synthesisof Thalidomide

from achiralstarting materials

N

O

O

N

O

O H

H

N

O

O

N

O

O H

H

S R

+

1 : 1(r a c e m ic m ix t u r e )

Se p a r a t e e n a n t iom e r s

(R eso lu t io n )

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Resolution of Enantiomers


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E n a n t i o m e r s a r e t e m p or a r ily con ve r t e d in t o a p a i r

o fd i a s t e r e o m e r s b y a d d in g a c h ir a l r e a g e n t .

R-th a lidom ide + S -th a lidom id e

Ad d a c h ir a lr e a ge n t (C*)

R -C* + S-C*

C* = 1 o r m or es t e r e o c e n t e r s

e n a n t i o m e r s

(sam e p roper t ies)

d i a s t e r e o m e r s

(d i f f eren t p roper t ies )i .e. d i f feren t b oi lin g

poin ts

Se p a r a t e b y

dis t i l l a t ion

R -C* S-C*

Clea ve off th e

ch ir a l r e a g en t

R - Th a l i d o mi d e S-Tha l idomideS e p a r a t e de n a n t i o m e r s

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Conclusions


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Conclusions

Some organic molecules possess one or more(n) stereocenters,thus several (2n) stereoisomersare possible.

Enantiomers and diastereomers differ only inthe position of atoms in space.

Unlike Diastereomers, Enantiomers displaythe same chemical/physical properties in anachiral environment.

In the human body (chiral environment) twoenantiomers can be discriminated producing

different biological responses.40

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