Make me a molecule
Rearrangement of atoms: cleaving and making bonds
Aspirin
Tagamet®
Tamiflu®
SYNTHESIS
Make me a molecule
“Chemists make molecules… they study the
properties of these molecules; …”
“At heart of their science is the molecule that is made.”
― Roald Hoffmann―
Constructing complex molecules is both an art
and a science which stretches the chemist’s
knowledge and insight, practical skills and
imagination.
Synthesis is the bedrock on which
the chemical and pharmaceutical
industries are built.
In
the beginning synthesis was unnecessary. Chemistry was
founded upon the study of those materials which were
available from natural sources. Many of the materials we
use today are made by chemical synthesis. Most of the
new compounds made today are organic.
Organic Chemistry
Organic Compounds
Most of the new compounds made today are organic,
that is, they are composed largely of carbon.
C C H
C C O C
C
C H
N
C
O O
C Cl
C
C
C
stable and versatile
C
N N
C
unstable
Product
e.g. paint and pigment
vitamin
synthetic fiber
pesticide
plastic
explosive pharmaceutical
Synthesis involves breaking and making new
chemical bonds to create new chemical structures.
e.g. Aspirin
In 400 B.C., the Greek physician Hippocrates
recommended chewing bark of the willlow tree
to alleviate the pain of childbirth and to treat eye
infections. *It is known in ancient Egypt .
CH2OH
Salicin
active
component
 Hydrolysis of salicin in aqueous acid gives
salicyl alcohol, which can be oxidized to
salicylic acid.
 Salicylic acid proved to be an even more
effective pain reliever. Unfortunately, it causes
severe irritation of stomach.
O glucose
CH2OH
O H
O
C OH
Saliciylic
acid
O H
O
 In 1883, chemists at Bayer division of I. G.
Farben in Germany prepared aspirin. It proved to
be less irritating to the stomach than salicylic acid
and also more effective in relieving the pain and
inflammation of rheumatoid arthritis.
Salicyl
alcohlol
O
H3C C O C CH3
O
C OH
O C CH3
O
Acetylsalicylic
acid
(Asprin)
Organic Synthesis:
1. Carbon-Carbon Bond Formation
2. Functional Group Interconversion
Efficiency and selectivity are important
characteristics that have to be taken into account.
[Efficiency: yields, number of steps]
[Selectivity: chemoselectivity, regioselectivity, stereoselectivity]
Organic Synthesis:
Stereoselectivity
1. Carbon-Carbon Bond Formation
2. Functional Group Interconversion
Organic Synthesis:
Enantioselectivity
1. Carbon-Carbon Bond Formation
2. Functional Group Interconversion
분자식
입체이성질체(Stereoisomers)
Cl
C2H2Cl2
Cl
C
H
C7H14
C
C
H
H
cis-1,2-dichloroethylene
(bp: 60 oC)
Cl
H
H
Cl
trans-1,2-dichloroethylene
(bp: 48 oC)
Me H
H
Me Me
H Me
cis
trans
CH2CH3
CH3CH2
C HI
C 4H 9I
CH3
(+)-2-iodobutane
(bp: 119 oC)
Chiral compounds
“Enantiomer”
C
H C
I
CH3
(-)-2-iodobutane
(bp: 119 oC)
아카티넬라 데코라 (하와이)
암피드로무스 (동남아시아)
Chiral Compounds
CH2CH3
CH3CH2
H C
I
C HI
CH3
CH3
(+)-2-iodobutane
(bp: 119 oC)
(-)-2-iodobutane
(bp: 119 oC)
[ ]D = +15.9
[ ]D = -15.9
Enatiomers
Optical isomers
They are optically active.
Some Physical Properties of the Stereoisomers of Tartaric Acid
HO
H NH2
HO
(S) 도파 (R)
N
H2N H
OH
심각한 부작용
파킨슨병 치료
H3C
OH
HOOC
COOH
H
H
N
CH3
(S) 케타민 (R)
Cl O
O Cl
환각제
마취제
H3C CH3
H3C
COOH
(S) 페니실아민 (R)
H3C CH3
HOOC
H2N H
H
OH
결핵치료
HO
OH
N
H
NH2
돌연변이유도
관절염치료
H
N
CH3
(S,S) 에탐부톨 (R,R)
N
H
H
N
HO
시력상실
O
O
H
H
O
N
N
H
O
O
(S) 탈리도미드 (R)
O
N
N
O
H
기형아 생성
HO
O
O
진정제
H O
H
N
H NH2H
O
(S,S) 아스파탐 (R,R)
O
¾´¸À
O
H2N
O
OH
(S) 아스파라진 (R)
N H
H2
NH2
HO
H N O
H2
¾´¸À
´Ü¸À
CH3
CH3
(S) 리모넨 (R)
·¹ ¸ó Çâ
O
N
H
H2N H
O
O
´Ü¸À
O
O
¿À·» ÁöÇâ
OH
Louis Pasteur was born on December 27,
1822 in Dole, in the region of Jura, France.
Louis Pasteur
Chemist
Resolution of enantiomers
in 1848
1822-1895
Twenty years later, J. H. van’t Hoff and J.-A. Le Bel
independently explained the origins of enantiomers based
on the tetrahedral nature of carbon bonding.
“Chance favors only prepared mind.”
-Louis Pasteur
Resolution
diastereomeric salts  seperation by selective crystallization
or some other means
Once separated, acidification of the two diastereomeric salts with strong acid
gives pure enantiomers and recover the chiral amine.