254
NUCLEOPHILIC REACTIONS OF CARBONYL GROUPS
An interesting extension of the acid-catalysed equilibrium reaction is the process termed transesterification. If an ester is treated with an excess of an
alcohol and an acid catalyst, then the ester OR group
becomes replaced by the alcohol OR group. This
reaction proceeds through a tetrahedral intermediate
containing both types of OR group, and the product thus depends upon disturbing the equilibrium by
using an excess of one or other of the two alcohols.
A base-catalysed process may also be used in transesterification.
OH
R
OMe
OH
R
OEt
O
R
OEt
O
R
OMe
OH
R
OMe
O
OH
R
O
OEt
Me
H
Et
H
acid-catalysed transesterification
methyl ester
ethyl ester
− H
+
, + H
+
alcohol in excess
EtOH
H
MeOH
H
Box 7.13
Transesterification: aspirin as an acetylating agent
The mode of action of the analgesic aspirin is now known to involve a transesterification process. Aspirin
(acetylsalicylic acid) exerts its action by acetylating the enzyme cyclooxygenase (COX) that is involved in
the biosynthesis of prostaglandins (see Box 9.3). Prostaglandins are modified C 20 fatty acids found in small
quantities in animal tissues and they affect a wide variety of physiological processes, such as blood pressure,
gastric secretion, smooth muscle contraction and platelet aggregation. Inflammation is a condition that occurs as a
direct result of increased prostaglandin synthesis, and many of the non-steroidal anti-inflammatory drugs, such as
aspirin and ibuprofen, exert their beneficial effects by reducing prostaglandin formation. Aspirin is able to do this
by specifically acetylating the hydroxyl of a serine residue in COX, thus inactivating the enzyme and stopping
the biosynthetic pathway to prostaglandins:
O
CO 2 H
CH 3
O
Ser
OH
OH
salicylic acid
transesterification
enzyme COX
Ser
O
acetylated enzyme
O
CH 3
acetylsalicylic acid
aspirin
CO 2 H
prostaglandins
prostaglandins
original ester
new alcohol
new ester
original alcohol
We shall meet another important example of transesterification in the action of the enzyme acetylcholinesterase
(see Box 13.4).
NUCLEOPHILIC REACTIONS OF CARBONYL GROUPS
An interesting extension of the acid-catalysed equilibrium reaction is the process termed transesterification. If an ester is treated with an excess of an
alcohol and an acid catalyst, then the ester OR group
becomes replaced by the alcohol OR group. This
reaction proceeds through a tetrahedral intermediate
containing both types of OR group, and the product thus depends upon disturbing the equilibrium by
using an excess of one or other of the two alcohols.
A base-catalysed process may also be used in transesterification.
OH
R
OMe
OH
R
OEt
O
R
OEt
O
R
OMe
OH
R
OMe
O
OH
R
O
OEt
Me
H
Et
H
acid-catalysed transesterification
methyl ester
ethyl ester
− H
+
, + H
+
alcohol in excess
EtOH
H
MeOH
H
Box 7.13
Transesterification: aspirin as an acetylating agent
The mode of action of the analgesic aspirin is now known to involve a transesterification process. Aspirin
(acetylsalicylic acid) exerts its action by acetylating the enzyme cyclooxygenase (COX) that is involved in
the biosynthesis of prostaglandins (see Box 9.3). Prostaglandins are modified C 20 fatty acids found in small
quantities in animal tissues and they affect a wide variety of physiological processes, such as blood pressure,
gastric secretion, smooth muscle contraction and platelet aggregation. Inflammation is a condition that occurs as a
direct result of increased prostaglandin synthesis, and many of the non-steroidal anti-inflammatory drugs, such as
aspirin and ibuprofen, exert their beneficial effects by reducing prostaglandin formation. Aspirin is able to do this
by specifically acetylating the hydroxyl of a serine residue in COX, thus inactivating the enzyme and stopping
the biosynthetic pathway to prostaglandins:
O
CO 2 H
CH 3
O
Ser
OH
OH
salicylic acid
transesterification
enzyme COX
Ser
O
acetylated enzyme
O
CH 3
acetylsalicylic acid
aspirin
CO 2 H
prostaglandins
prostaglandins
original ester
new alcohol
new ester
original alcohol
We shall meet another important example of transesterification in the action of the enzyme acetylcholinesterase
(see Box 13.4).