RADICAL ADDITION OF OXYGEN: AUTOXIDATION REACTIONS
339
Box 9.3
Radical oxidations in prostaglandin biosynthesis: cyclooxygenase
In Box 7.13 we saw that the widely used analgesic aspirin exerted its action by acetylating the enzyme
cyclooxygenase (COX) which is involved in the production of prostaglandins. Prostaglandins are modified
C 20 fatty acids synthesized in animal tissues and they affect a wide variety of physiological processes, such as
CO 2 H
O
O
CO 2 H
O
O
O OH
cyclooxygenase
(COX)
PGG 2
cyclic
peroxide
acyclic peroxide
peroxyl radical finally
abstracts hydrogen atom
CO 2 H
CO 2 H
CO 2 H
H
arachidonic acid
O
O
CO 2 H
O
O
O O
CO 2 H
O
O
O O
radical addition to O 2 and
formation of peroxyl radical
resonance stabilization of
radical; the conjugated
structure is preferred
concerted addition of radical to double
bonds with formation of cyclopentane
ring and generation of allylic radical;
see stepwise sequence below
radical addition to
second O 2 molecule
CO 2 H
O
O
CO 2 H
O
O
CO 2 H
O
O
CO 2 H
O
O
stepwise cyclization sequence:
addition of radical to alkene
addition of radical to alkene
resonance stabilization of allylic radical
the allylic methylene flanked by
double bonds is most susceptible
to hydrogen abstraction