452
HETEROCYCLES
Box 11.12 (continued)
but theophylline is much more important as a drug compound because of its muscle relaxant properties, utilized
in the relief of bronchial asthma.
N
N
N
N
O
O
Me
Me
Me
HN
N
N
N
O
O
Me
Me
theobromine
caffeine
N
N
N
H
N
O
O
Me
theophylline
Me
These compounds competitively inhibit phosphodiesterase, resulting in an increase in cyclic AMP (see
Box 14.3) and subsequent release of adrenaline. This leads to the major effects: a stimulation of the central
nervous system (CNS), a relaxation of bronchial smooth muscle, and induction of diuresis. These effects vary in
the three compounds. Caffeine is the best CNS stimulant, and has weak diuretic action. Theobromine has little
stimulant action, but has more diuretic activity and also muscle relaxant properties. Theophylline also has low
stimulant action and is an effective diuretic, but it relaxes smooth muscle better than caffeine or theobromine.
It has been estimated that beverage consumption may provide the following amounts of caffeine per cup
or average measure: coffee, 30–150 mg (average 60–80 mg); instant coffee, 20–100 mg (average 40–60 mg);
decaffeinated coffee, 2–4 mg; tea, 10–100 mg (average 40 mg); cocoa, 2–50 mg (average 5 mg); cola drink,
25–60 mg. The maximal daily intake should not exceed about 1 g to avoid unpleasant side effects, e.g. headaches,
restlessness. An acute lethal dose is about 5–10 g.
Caffeine and theobromine may be obtained in large quantities from natural sources, or they may be obtained
by total or partial synthesis. Theophylline is usually produced by total synthesis.
11.9.2 Pteridines
In pteridines, we have a pyrimidine ring fused to
a pyrazine ring. There are, of course, a number
of possible ways of combining these two sixmembered ring systems; pteridines are pyrazino[2,3d]pyrimidines (see Section 11.9).
We do not want to consider the chemistry of
the pteridine ring system here, but instead we
shall look at the structures of two rather important
pteridine-based biochemicals, namely folic acid and
riboflavin. In the latter case, the pteridine is also
fused further to a benzene ring, giving an even
more complex ring system, a benzo[g]pteridine. The
accompanying diagram shows the derivation of the
fused-ring nomenclature. The oxygenated form of the
benzopteridine found in riboflavin is also called an
isoalloxazine.
N
N
N
N
pyrimidine
pyrazine
a
b
c
d
1
2
3
4
N
N
N
N
pteridine
pyrazino[2,3-d]pyrimidine
benzo[g]pteridine
N
N
N
N
6
5
7
8
N
N
N
N
a
b
c
d e
f
g
Box 11.13
Folic acid
Folic acid (vitamin B 9 ) is a conjugate of a pteridine unit, p-aminobenzoic acid, and glutamic acid. Deficiency
of folic acid leads to anaemia, and it is also standard practice to provide supplementation during pregnancy to
reduce the incidence of spina bifida.
HETEROCYCLES
Box 11.12 (continued)
but theophylline is much more important as a drug compound because of its muscle relaxant properties, utilized
in the relief of bronchial asthma.
N
N
N
N
O
O
Me
Me
Me
HN
N
N
N
O
O
Me
Me
theobromine
caffeine
N
N
N
H
N
O
O
Me
theophylline
Me
These compounds competitively inhibit phosphodiesterase, resulting in an increase in cyclic AMP (see
Box 14.3) and subsequent release of adrenaline. This leads to the major effects: a stimulation of the central
nervous system (CNS), a relaxation of bronchial smooth muscle, and induction of diuresis. These effects vary in
the three compounds. Caffeine is the best CNS stimulant, and has weak diuretic action. Theobromine has little
stimulant action, but has more diuretic activity and also muscle relaxant properties. Theophylline also has low
stimulant action and is an effective diuretic, but it relaxes smooth muscle better than caffeine or theobromine.
It has been estimated that beverage consumption may provide the following amounts of caffeine per cup
or average measure: coffee, 30–150 mg (average 60–80 mg); instant coffee, 20–100 mg (average 40–60 mg);
decaffeinated coffee, 2–4 mg; tea, 10–100 mg (average 40 mg); cocoa, 2–50 mg (average 5 mg); cola drink,
25–60 mg. The maximal daily intake should not exceed about 1 g to avoid unpleasant side effects, e.g. headaches,
restlessness. An acute lethal dose is about 5–10 g.
Caffeine and theobromine may be obtained in large quantities from natural sources, or they may be obtained
by total or partial synthesis. Theophylline is usually produced by total synthesis.
11.9.2 Pteridines
In pteridines, we have a pyrimidine ring fused to
a pyrazine ring. There are, of course, a number
of possible ways of combining these two sixmembered ring systems; pteridines are pyrazino[2,3d]pyrimidines (see Section 11.9).
We do not want to consider the chemistry of
the pteridine ring system here, but instead we
shall look at the structures of two rather important
pteridine-based biochemicals, namely folic acid and
riboflavin. In the latter case, the pteridine is also
fused further to a benzene ring, giving an even
more complex ring system, a benzo[g]pteridine. The
accompanying diagram shows the derivation of the
fused-ring nomenclature. The oxygenated form of the
benzopteridine found in riboflavin is also called an
isoalloxazine.
N
N
N
N
pyrimidine
pyrazine
a
b
c
d
1
2
3
4
N
N
N
N
pteridine
pyrazino[2,3-d]pyrimidine
benzo[g]pteridine
N
N
N
N
6
5
7
8
N
N
N
N
a
b
c
d e
f
g
Box 11.13
Folic acid
Folic acid (vitamin B 9 ) is a conjugate of a pteridine unit, p-aminobenzoic acid, and glutamic acid. Deficiency
of folic acid leads to anaemia, and it is also standard practice to provide supplementation during pregnancy to
reduce the incidence of spina bifida.